Autism/ASD and Dementia

Tatja Hirvikoski, Ellenor Mittendorfer-Rutz, Marcus Boman, Henrik Larsson, Paul Lichtenstein & Sven Bolte

British Journal of Psychiatry (2016). 208, 232–238. doi: 10.1192/bjp.bp.114.160192

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Abstract: Mortality has been suggested to be increased in autism spectrum disorder (ASD). Study examined both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability. Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185). During the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38–2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analyzed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability. Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.

Barnard-Brak, L., Richman, D., & Yang, Z.

Advances in Autism, 2019, 5(4). 26 September 2019.  https://www.emerald.com/insight/content/doi/10.1108/AIA-11-2018-0045/full/html

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Abstract: Autism spectrum disorder (ASD) is a lifelong disorder that requires intervention and support services for a growing geriatric population. The purpose of this paper is to examine the mean age at death of individuals with ASD and subsequent comorbidity with Alzheimer’s disease, and any form of dementia, as a whole and according to sex. Data consisted of 1,754 individuals who had an ASD listed as one of the causes of deaths from the National Vital Statistics System with data from 1999 to 2015. In the current study, the authors present contradictory results with a mean age at death for individuals with ASD was 68 years by adjusting for changing prevalence rates. Females with ASD had a higher mean age at death than males with ASD; consistent with the trend in the sex differences in the general population. The results of the current study also indicate that individuals with ASD were, in fact, less likely than the general population to have Alzheimer’s disease or a form of dementia. However, males with ASD were significantly more likely to have acquired Alzheimer’s disease or a form of dementia as compared to females with ASD. Guan and Li (2017) reported a mean age at death of 36 years old for individuals with ASD, which was subsequently reported in the mass media, most notably CNN. The authors contend that this study provides a more accurate estimate mean age at death.

Mason D, Stewart GR, Capp SJ, Happé F., Autism Adulthood, 2022 Jun 1;4(2):164-172. doi: 10.1089/aut.2021.0041. Epub 2022 Jun 9. PMID: 36605971; PMCID: PMC9645679.

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Abstract:  There is a paucity of research involving older autistic people, as highlighted in a number of systematic reviews. However, it is less clear whether this is changing, and what the trends might be in research on autism in later life. Authors conducted a broad review of the literature by examining the number of results from a search in three databases (PubMed, Embase, PsycINFO) across four age groups: childhood, adolescence, adulthood, and older age. They also examined the abstracts of all the included articles for the older age group and categorized them under broad themes. Their database search identified 145 unique articles on autism in older age, with an additional 67 found by the authors (hence, the total number of articles in this review is 212). Since 2012, we found a 392% increase
in research with older autistic people, versus 196% increase for childhood/early life, 253% for adolescence, and 264% for adult research. They identified 2012 as a point at which, year-on-year, older age autism research started increasing, with the most commonly researched areas being cognition, the brain, and genetics. However, older adult research only accounted for 0.4% of published autism studies over the past decade. This increase reflects a positive change in the research landscape, although research with children continues to dominate. We also note the difficulty of identifying papers relevant to older age autism research, and propose that a new keyword could be created to increase the visibility and accessibility of research in this steadily growing area.

Crawford, D., Abner, E., Glaser, P., & Jicha, G.

Neurology, 2014, April 08, 2014; 82 (10 Supplement)

https://n.neurology.org/content/82/10_Supplement/I4-1.009

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Abstract: Study designed to evaluate the presence of autistic symptoms in a geriatric cohort with mild cognitive impairment and early dementia. Autistic spectrum disorders (ASD) vary in age of onset, but are classically diagnosed by adolescence or early adulthood at latest. The possibility that development of late life ASD may occur has been poorly explored. Recent studies have suggested that late life onset of ASD symptoms can develop in frontotemporal dementia, but have not been linked to the development of other dementias or mild cognitive impairment (MCI). In order to characterize late- life ASD symptoms in MCI and dementia, we surveyed the caregivers of 140 subjects with late-life cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the GARS-II. Eighty-one subjects returned the survey for a response rate of 58%. Subjects with the highest autism index ratings reported significantly younger age at onset of decline than those who scored in the ‘Unlikely’ range (n=49): 68.2±9.3 vs 74.9±7.9 (p < 0.01). This remains true when the respondents were restricted to just those cases with dementia (n=13 and n=33): 67.7±9.4 vs. 74.0±8.8 (p < 0.05). These data demonstrate that ASD symptoms are associated with late-life degenerative dementia and that such symptoms are more prevalent in those with early vs. late onset dementia. It is possible that lifelong subclinical ASD tendencies, might manifest only when neurological function is compromised by the development of even the mildest of pathologic insults in geriatric years. Further work examining the interplay between ASD and late life dementia could help identify key areas of shared neuroanatomic involvement between ASD and late life dementias, and provide valuable insights that might hasten the development of therapeutic strategies for both ASD and behavioral features seen in MCI and dementia states.

Khan, S.A., Khan, S.A., Narendra, A.R., Mushtaq, G., Zahran, S.A., Khan, S., & Kamal, M.A.

CNS Neurol Disord Drug Targets, 2016;15(4):390-402. doi: 10.2174/1871527315666160321104303.

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Abstract: Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders respectively, with devastating effects not only on the individual but also the society. Collectively, a number of factors contribute to the expression of ASD and AD. It is of utmost curiosity that these disorders express at different stages of life and there is an involvement of certain susceptible genes. This genetic basis makes the background of common associations like memory deficits, cognition changes, demyelination, oxidative stress and inflammation, an integral part of both disorders. Modern technology resulting in genetically modified crops and increase in gadgets emitting electromagnetic frequencies have resulted in enhanced risks for neurological dysfunctions and disorders like ASD and AD. Subsequent advances in the psychological, pharmacological, biochemical and nutritional aspects of the disorders have resulted in the development of newer therapeutic approaches. The common clinical features like language impairment, executive functions, and motor problems have been discussed along with the patho-physiological changes, role of DNA methylation, myelin development, and heavy metals in the expression of these disorders. Psychopharmacological and nutritional approaches towards the reduction and management of risk factors have gained attention from the researchers in recent years. Current major therapies either target the inflammatory pathways or reduce cellular oxidative stress. This article focuses on the commonalities of the two disorders.

Janicki, M.P., Henderson, C.M., Rubin, I.L. & Neurodevelopmental Conditions Study Group

Disability and Health Journal, 2008, Apr, 1(2), 116-24.  doi: 10.1016/j.dhjo.2008.02.004.

 

Abstract: This article provides a summary of the proceedings of the Neurodevelopmental Conditions Study Group charrette held on May 21-22, 2007, in Atlanta, Georgia (USA) and underwritten by the Developmental Disabilities Branch of the U.S. Centers for Disease Control and Prevention and the National Institute for Disability and Rehabilitation Research. The charrette was a part of the conference on "State of the Science in Aging with Developmental Disabilities: Charting Lifespan Trajectories and Supportive Environments for Healthy Living." The aim of the charrette was to examine the extant knowledge on aging-related long-term effects and interactions of a number of neurodevelopmental conditions, including autism, cerebral palsy, Down syndrome, fragile X syndrome, Prader-Willi syndrome, spina bifida, and Williams syndrome. The discussants noted that although there is some published information regarding lifespan changes with these disorders, especially cerebral palsy and Down syndrome, there is a lack of confirming evidence for most of these conditions and concluded that additional evidence-based research and investigatory clinical work are needed to better understand the long-term effects of maturation and aging upon adults with these conditions. Primary recommendations included a call for more work toward the identification and description of the presentations and courses of age-related medical disorders that are common among these conditions; determination of the comparative prevalence and incidence of specific medical conditions between persons with neurodevelopmental disabilities and the general population; use of prevalence and incidence data to better understand risk factors for concomitant conditions; promotion of surveillance, screening, and specific treatment protocols for health provision; institution of a program of translational collaborative research related to older-age associated conditions; and dissemination of information related to aging and health to providers and people affected by these conditions.

Ahanger, I.A., Sharma, A., Islam, A.

In: Md Ashraf, G., Alexiou, A. (eds.), Autism Spectrum Disorder and Alzheimer's Disease. (pp 43–61), 2021.  Springer, Singapore. https://doi.org/10.1007/978-981-16-4558-7_3

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Abstract:  Autism spectrum disorder (ASD) is a neurodevelopmental disability that is associated with the promotion of social, communication, and behavioral inflexibility or impairment in an individual, whereas Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by degeneration and death of brain cells and ultimately leads to dementia and cognitive decline. However, reports suggest that both share common neuronal proteins including amyloid precursor protein (APP), phosphatase and tensin homolog (PTEN), fragile X mental retardation protein, and metabotropic glutamate receptors. Here, the correlation between neuronal proteins of these two diseases is highlighted. The significance of common signaling pathway is illustrated though the NOWADA model. The brains of individuals with ASD exhibit the phenomenon of hyperplasticity that can be very crucial in tackling AD. This study reviewed medications approved for AD (including donepezil, galantamine, rivastigmine, tacrine, and memantine) which have also shown potential effectiveness in individuals with ASD. More vigorous investigations are obligatory as there is an absence of medication for ADS and AD. Through overviewing the recent advances and trends regarding ASD and its correlation with AD can be fundamentally conducive in understanding mechanism of etiology of ASD and AD and formulating the ultra-efficient therapeutic approach to impediment complications due to these diseases.

Midorikawa A. & Kawamura M

Dementia and Geriatric Cognitive Disorders Extra, 2012, 2, 180–186. https://doi.org/10.1159/000338174

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​Abstract: The existence of the behavioral variant of frontotemporal dementia (bv-FTD), including senile Asperger’s syndrome (AS), has been proposed. However, there are no empirical case reports to support the proposal. In this report, we present 3 patients who showed symptoms of bv-FTD and demonstrated signs of autistic spectrum disorder, especially AS. We evaluated 3 subjects using the diagnostic criteria for bv-FTD, and their caregivers retrospectively provided data to calculate the Autism-Spectrum Quotient, Japanese version [Wakabayashi et al.: Shinrigaku Kenkyu 2004;75:78–84]. We also compared these data with those obtained from 3 individuals with Alzheimer’s disease.  All 3 patients met the criteria for bv-FTD and had a higher Autism-Spectrum Quotient score than did comparable Alzheimer’s disease subjects. It is possible that some senile persons with frontotemporal lobar degeneration-like maladaptive behavior may also have subclinical AS.

Mason D, Stewart GR, Capp SJ, Happé F.

Autism Adulthood. 2022 Jun 1;4(2):164-172. doi: 10.1089/aut.2021.0041.

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​Abstract:  There is a paucity of research involving older autistic people, as highlighted in a number of systematic reviews. However, it is less clear whether this is changing, and what the trends might be in research on autism in later life. We conducted a broad review of the literature by examining the number of results from a search in three databases (PubMed, Embase, PsycINFO) across four age groups: childhood, adolescence, adulthood, and older age. We also examined the abstracts of all the included articles for the older age group and categorized them under broad themes. Our database search identified 145 unique articles on autism in older age, with an additional 67 found by the authors (hence, the total number of articles in this review is 212). Since 2012, we found a 392% increase in research with older autistic people, versus 196% increase for childhood/early life, 253% for adolescence, and 264% for adult research. We identify 2012 as a point at which, year-on-year, older age autism research started increasing, with the most commonly researched areas being cognition, the brain, and genetics. However, older adult research only accounted for 0.4% of published autism studies over the past decade. This increase reflects a positive change in the research landscape, although research with children continues to dominate. We also note the difficulty of identifying papers relevant to older age autism research, and propose that a new keyword could be created to increase the visibility and accessibility of research in this steadily growing area.

Axmon A, Kristensson J, Ahlström G, Midlöv P., Res Dev Disabil. 2017 Mar;62:50-57. doi: 10.1016/j.ridd.2017.01.001. Epub 2017 Jan 18. PMID: 28110116.

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Abstract: Although people with intellectual disability (ID) and people with dementia have high drug prescription rates, there is a lack of studies investigating drug use among those with concurrent diagnoses of ID and dementia. Authors investigated the use of antipsychotics, benzodiazepine derivatives, and drugs recommended for dementia treatment (anticholinesterases [AChEIs] and memantine) among people with ID and dementia. Having received support available for people with ID and/or autism spectrum disorder (ASD) was used as a proxy for ID. The ID cohort consisted of 7936 individuals, aged at least 55 years in 2012, and the referent cohort of age- and sex-matched people from the general population (gPop). People with a specialists' diagnosis of dementia during 2002-2012 were identified (ID, n=180; gPop, n=67), and data on prescription of the investigated drugs during the period 2006-2012 were collected. : People with ID/ASD and dementia were more likely than people with ID/ASD but without dementia to be prescribed antipsychotics (50% vs 39% over the study period; odds ratio (OR) 1.85, 95% confidence interval 1.13-30.3) and benzodiazepine derivatives (55% vs 36%; OR 2.42, 1.48-3.98). They were also more likely than people with dementia from the general population to be prescribed antipsychotics (50% vs 25%; OR 3.18, 1.59-6.34), but less likely to be prescribed AChEIs (28% vs 45%; OR 0.32, 0.16-0.64).

Midorikawa, A.

Brain Nerve, 2015 Sep;67(9):1125-32. doi: 10.11477/mf.1416200271.

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Abstract: This article reviews the relationship between developmental disorders and dementia with ageing. Persons with autistic spectrum disorder (ASD) are vulnerable to life events, even in their old age. In certain cases, senile persons with undiagnosed ASD, who developed maladaptive behaviors after negative life events, were considered as having a behavioral variant of frontotemporal dementia (bvFTD). However, to our knowledge, there are no reports on the relationships between ASD and bvFTD. Alternatively, there are only a limited number of reports, which address the relationships between developmental disorders and dementia. One such relationship is that in patients with dementia with Lewy bodies (DLB) and those with Parkinson's disease (PD), who also show a tendency for having attention-deficit/hyperactivity disorder (ADHD) at a younger age. Another such relationship is seen in patients with primary progressive aphasia (PPA) who show a high occurrence of learning disability (LD) among their first-degree relatives. These results imply that the neurotransmitter pathway or language network in the brain is vulnerable in some subjects. These retrospective studies have demonstrated a possible relationship between developmental disorders and dementia; however, no study has shown a causality of developmental disorders and dementia.

Elizabeth K. Rhodus, Justin M. Barber, Shoshana H. Bardach, Peter T. Nelson, & Gregory A. Jicha

Alzheimer’s & Dementia, .2020;16(Suppl.2):e043927., DOI:10.1002/alz.043927. 

https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.043927

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​Abstract: Previous clinical studies have described autism spectrum-like behaviors in approximately 16% of late-onset dementia cases.The neuropathologic substrate for such behaviors is currently unknown, but may shed light on shared neuroanatomic and molecular pathways involved in these otherwise distinct forms of brain dysfunction. This study investigates the hypothesis that subjects with late onset dementia associated with autism-like behaviors will exhibit increased pathologic features in both the frontal and parietal association cortices. An age, education, and sex-matched case-control design was used. Subjects were recruited from the University of Kentucky Alzheimer Disease Center longitudinal autopsy cohort. Subjects had a diagnosis of MCI or dementia at the time of completion of the Gilliam Autism Rating Scale-2(GARS-2) in addition to standard clinical, genetic,and cognitive assessments (n=148). Those who have come to autopsy demonstrating either no evidence of (n=24) or a high level of (n=19) autism-like behaviors on the GARS-2 were included.  Comprehensive neuropathologic evaluation included assessment of all common late-life dementia pathologies using both semi-quantitative rating scales and digital quantitative measures of global and regional pathological features. Between group analyses demonstrated no significant differences in age, education, sex, clinical diagnosis, or apoE4 status. High-autism vs. no-autism cases scored significantly higher on the Clinical Dementia Rating scale (p<0.05).  Approximately 80% of cases had a primary pathologic diagnosis of Alzheimer’s disease, with the remaining 20% of individuals demonstrating pathologic features consistent with Late (16%), cerebrovascular (2%), or Lewy body disease (2%). No cases had frontotemporal lobar degeneration (FTLD) as a primary or comorbid pathology. Quantitative measures of neurofibrillary tangles and tau burden were higher in the frontal lobes of high-autism subjects compared to the matched no-autism controls(p<0.02). These data are the first to link autism-like behaviors to increased levels of tau and neurofibrillary pathology in the frontal lobes at autopsy in subjects with late-life dementia. Yet, the present data demonstrate that FTLD pathology is not a major contributor to such behaviors in a community-based cohort of late-life dementia. Further work understanding potential links between tau-mediated neurodegeneration and autism-like behavior is warranted.

A. Roestorf, D. M. Bowler, M. K. Deserno, P. Howlin, L. Klinger, H. McConachie, J. R. Parr, P. Powell, B. F. C. Van Heijst, & H. M. Geurts

Research in Autism Spectrum Disorders, 2019, Jul; 63, 3-12.  doi:10.1016/j.rasd.2018.08.007.

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Abstract: A special interest group (SIG) meeting, titled "Older Adults with ASD: The Consequences of Aging", was held at the International Society for Autism Research (INSAR) annual meetings in 2016 and 2017. The SIG and subsequent meetings brought together, for the first time, international delegates who were members of the autistic community, researchers, practitioners, and service providers. Based on aging autism research that is already underway in UK, Europe, Australia and North America, discussions focused on conceptualizing the parameters of aging when referring to autism, and the measures that are appropriate to use with older adults when considering diagnostic assessment, cognitive factors, and quality of life in older age. Thus, the aim of this SIG was to progress the research agenda on current and future directions for autism research in the context of aging. A global issue on how to define 'aging' when referring to ASD was at the forefront of discussions. The ‘aging’ concept can in principle refer to all developmental transitions. However, in this paper we focus on the cognitive and physical changes that take place from mid-life onward. Accordingly, it was agreed that aging and ASD research should focus on adults over the age of 50 years, given the high rates of co-occurring physical and mental health concerns and increased risk of premature death in some individuals. Moreover, very little is known about the cognitive change, care needs and outcomes of autistic adults beyond this age. Discussions on the topics of diagnostic and cognitive assessments, and of quality of life and well-being were explored through shared knowledge about which measures are currently being used and which background questions should be asked to obtain comprehensive and informative developmental and medical histories. Accordingly, a survey was completed by SIG delegates who were representatives of international research groups across four continents, and who are currently conducting studies with older autistic adults. Considerable overlap was identified across different research groups in measures of both autism and quality of life, which pointed to combining data and shared learning as the logical next step. Regarding the background questions that were asked, the different research groups covered similar topics, but the groups differed in the way these questions were formulated when working with autistic adults across a range of cognitive abilities. It became clear that continued input from individuals on the autism spectrum is important to ensure that questionnaires used in ongoing and future are accessible and understandable for people across the whole autistic spectrum, including those with limited verbal abilities.

Janina Ivashko-Pachima, Adva Hadar, Iris Grigg, Vlasta Korenková, Oxana Kapitansky, Gidon Karmon, Michael Gershovits, C. Laura Sayas, R. Frank Kooy, Johannes Attems, David Gurwitz & Illana Gozes

Molecular Psychiatry, 2019. https://doi.org/10.1038/s41380-019-0563-5

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​Abstract: With Alzheimer’s disease (AD) exhibiting reduced ability of neural stem cell renewal, we hypothesized that de novo mutations controlling embryonic development, in the form of brain somatic mutations instigate the disease. A leading gene presenting heterozygous dominant de novo autism-intellectual disabilities (ID) causing mutations is activity-dependent neuroprotective protein (ADNP), with intact ADNP protecting against AD-tauopathy. We discovered a genomic autism ADNP mutation (c.2188C>T) in postmortem AD olfactory bulbs and hippocampi. RNA-Seq of olfactory bulbs also identified a novel ADNP hotspot mutation, c.2187_2188insA. Altogether, 665 mutations in 596 genes with 441 mutations in AD patients (389 genes, 38% AD—exclusive mutations) and 104 genes presenting disease-causing mutations (OMIM) were discovered. OMIM AD mutated genes converged on cytoskeletal mechanisms, autism and ID causing mutations (about 40% each). The number and average frequencies of AD-related mutations per subject were higher in AD subjects compared to controls. RNA-seq datamining (hippocampus, dorsolateral prefrontal cortex, fusiform gyrus and superior frontal gyrus—583 subjects) yielded similar results. Overlapping all tested brain areas identified unique and shared mutations, with ADNP singled out as a gene associated with autism/ID/AD and presenting several unique aging/AD mutations. The large fusiform gyrus library (117 subjects) with high sequencing coverage correlated the c.2187_2188insA ADNP mutation frequency to Braak stage (tauopathy) and showed more ADNP mutations in AD specimens. In cell cultures, the ADNP-derived snippet NAP inhibited mutated-ADNP-microtubule (MT) toxicity and enhanced Tau–MT association. We propose a paradigm-shifting concept in the perception of AD whereby accumulating mosaic somatic mutations promote brain pathology.

Bishop-Fitzpatrick, L., & Rubenstein, E.

Research in Autism Spectrum Disorders, 2019, Jul, 63, 34-41.   doi:10.1016/j.rasd.2019.01.001. Epub 2019 Jan 29.

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Abstract: People on the autism spectrum may have more physical and mental health conditions in midlife and old age compared to the general population. This study describes the physical and mental health of a unique sample of all middle aged and older Wisconsin Medicaid beneficiaries with an autism spectrum disorder diagnosis and tests differences between those with and without co-occurring intellectual disability.  Using de-identified Medicaid claims data for 143 adults with a recorded autism spectrum disorder diagnosis aged 40–88 years with any Wisconsin Medicaid claims in 2012 through 2015, we extracted diagnoses for physical and mental health conditions from fee-for-service claims. Logistic regression analyses—controlling for sex, race, and age—compared the adjusted odds of physical and mental health conditions for those with and without intellectual disability.  Many physical and mental health conditions, including immune conditions (70.6%), cardiovascular disease (49.0%) and its risk factors (46.2%), sleep disorders (85.3%), gastrointestinal disorders (49.7%), neurologic conditions (55.9%), and psychiatric disorders (72.0%) were highly prevalent in our full sample. Although there were many similarities between those individuals with and without co-occurring intellectual disability, middle aged and older adults on the autism spectrum had higher prevalence of epilepsy and lower prevalence of depression and anxiety compared to those without co-occurring intellectual disability. Findings suggest that people on the autism spectrum have a high prevalence of physical and mental health conditions in midlife and old age, regardless of intellectual disability status.

Lucy Barnard-Brak, David Richman, & Zhanxia Yang

Advances in Autism, 2019, 5(4). 26 September 2019.  https://www.emerald.com/insight/content/doi/10.1108/AIA-11-2018-0045/full/html

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Abstract: Autism spectrum disorder (ASD) is a lifelong disorder that requires intervention and support services for a growing geriatric population. The purpose of this paper is to examine the mean age at death of individuals with ASD and subsequent comorbidity with Alzheimer’s disease, and any form of dementia, as a whole and according to sex. Data consisted of 1,754 individuals who had an ASD listed as one of the causes of deaths from the National Vital Statistics System with data from 1999 to 2015. In the current study, the authors present contradictory results with a mean age at death for individuals with ASD was 68 years by adjusting for changing prevalence rates. Females with ASD had a higher mean age at death than males with ASD; consistent with the trend in the sex differences in the general population. The results of the current study also indicate that individuals with ASD were, in fact, less likely than the general population to have Alzheimer’s disease or a form of dementia. However, males with ASD were significantly more likely to have acquired Alzheimer’s disease or a form of dementia as compared to females with ASD. Guan and Li (2017) reported a mean age at death of 36 years old for individuals with ASD, which was subsequently reported in the mass media, most notably CNN. The authors contend that this study provides a more accurate estimate mean age at death.

Mario F. Mendez, Jill S. Shapira, & Bruce L. Miller

Movement Disorder, 2005, 20(6), 742-746

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Abstract: Stereotypical movements are characteristic of autism or [intellectual disability] but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimer's disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received anti-psychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some self-injurious acts. All the FTD patients with stereotypical movements had compulsive-like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor

Stephen M. Edelson, David B. Nicholas, Kevin P. Stoddart, Margaret B. Bauman, Laurie Mawlam, Wenn B. Lawson, Caroline Jose, Rae Morris, & Scott D. Wright

Journal of Autism and Developmental Disorders, 2020, May 2,1-9. https://doi.org/10.1007/s10803-020-04514-3

 

Abstract: Over the past decade, there has been a growing interest in adults on the autistic spectrum, and more recently, the challenges related to aging in this population. A two-day Think Tank meeting, focused on aging in autism, was convened amongst international leaders in the field of autism research and practice. This meeting included a series of presentations addressing the current status of aging research, followed by discussions regarding priorities going forward. Attendees shared their thoughts and concerns regarding community services, government policies, societal perspectives and physical and mental health. The goal of these discussions was to consider systematic approaches aimed at providing meaningful supports that can ensure a quality of life for seniors on the autism spectrum. More research is needed regarding the role of co-occurring medical conditions in autism, including their symptomatic presentations and behavioral manifestations, how these medical conditions and symptomatic features may change with age, and how they can be accurately identified and effectively treated. We also need to learn more about specific health conditions associated with aging, such as arthritis, cancer, hypertension, diabetes, obesity, stroke, and dementia; and how these conditions manifest in autistic individuals. In addition, we need to know how autistic individuals respond to standard therapies commonly used to treat these conditions and if different, what therapeutic approaches would prove most effective in this population.

Elizabeth K Rhodus, Justin Barber, Erin L Abner, Danielle M C Duff, Shoshana H Bardach, Allison Caban-Holt, Donita Lightner, Graham D Rowles, Frederick A Schmitt, & Gregory A Jicha

Alzheimer Dis Assoc Disord. Jan-Mar 2020;34(1):66-71.doi: 10.1097/WAD.0000000000000345.

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Abstract: Autism spectrum disorder (ASD) represents a heterogeneous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has been poorly explored.  In order to more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in MCI and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2. Participants with high autism index ratings (Autism ‘Possible/Very Likely’, n=23) reported significantly (statistically and clinically) younger age at onset of cognitive impairment than those who scored in the Autism ‘Unlikely’ range (n=119): 71.14±10.9 vs. 76.65±8.25 (p = 0.034). Additionally, those in Autism ‘Possible/Very Likely’ group demonstrated advanced severity of cognitive impairment, indicated by Clinical Dementia Rating Scale Sum of Boxes scores. Data demonstrate that ASD behaviors may appear de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.

Oleguer Plana-Ripoll, Carsten Bøcker Pedersen, Yan Holtz, Michael E Benros, Søren Dalsgaard, Peter de Jonge, Chun Chieh Fan, et al. 

JAMA Psychiatry, 2019 Mar 1;76(3):259-270.  https.//doi: 10.1001/jamapsychiatry.2018.3658.

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Abstract: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity.  To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice. This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018. Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (e.g,, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated. A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). Some disorders were associated with substantial absolute risks of developing specific later disorders (e.g., 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years). Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders.

Lindsay M.Oberman & AlvaroPascual-Leone

Medical Hypotheses, 2014, Sept, 83(3), 337-342

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Abstract: Autism Spectrum Disorders (ASD) currently affects approximately 1% of the population causing grave disability and necessitating a better understanding of the currently enigmatic etiology of these disorders. Recent data suggest that some patients with ASD may have a dysfunction in brain plasticity (specifically data from animal models and human studies suggest a propensity toward excessive amount of plasticity). Plasticity is essential to the establishment and maintenance of brain circuitry; however, too much plasticity may lead to instability of structural connections and compromise of functional systems necessary for cognition and behavior. Multiple lines of evidence suggest that plasticity declines throughout the age-span and may underlie age-related cognitive decline. We hypothesize that individuals whose cortex begins as relatively “hyperplastic” (such as may be seen in ASD) should then be relatively protected from age-related cognitive decline (which we suggest is related to a reduction in plasticity). In the current study, we conducted a multiple linear regression using age and diagnosis as predictor variables in order to evaluate strength of the relationship between age, diagnosis or an interaction of the two factors and the degree of modulation in cortical excitability by transcranial magnetic stimulation as an index of cortical plasticity. Results indicate that across the age-span individuals with ASD show a consistently increased modulation of cortical excitability as compared to typically developing individuals, such that the general slope of decline across the age span is matched across both groups. We have argued that an individual’s risk of age-related cognitive decline (and risk for manifesting symptoms of dementia) depends on the individual’s starting point and slopes of change in plasticity efficiency over the lifespan. Therefore, our results suggest that individuals with ASD might be relatively protected from age-related cognitive decline and the risk of dementia.

Vivanti, G., Tao, S., Lyall, K., Robins, D.L., & Shea, L.L.

Autism Research,11 August 2021, https://doi.org/10.1002/aur.2590

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Abstract: The prevalence and incidence of early-onset dementia among adults with autism spectrum disorder (ASD) is currently unknown. In this case–control study, the prevalence and incidence of early-onset dementia in individuals with ASD was examined during 2008–2012 using Medicaid Analytic eXtract files. Participants were 30–64 year-old adults who were Medicaid beneficiaries and had either a diagnosis of ASD only (n = 12,648), a diagnosis of ASD with co-occurring intellectual disability (ID) (n = 26,168), a diagnosis of ID without ASD (n = 406,570), or no ASD nor ID diagnoses (n = 798,828). The 5-year prevalence of dementia was 4.04% among adults with ASD only, and 5.22% for those with ASD and co-occurring ID. This prevalence was higher compared to the prevalence of dementia in individuals with no ASD and no ID (0.97%), but lower compared to individuals with ID only (7.10%). Risk factors associated with the increased prevalence in the general population were similarly associated with the increased risk of dementia in individuals with ASD. Even after adjusting for these risk factors, compared to the general population, dementia was found to occur more frequently in individuals with ASD only (adjusted hazard ratio, 1.96; 95% CI, 1.69–2.28), as well as individuals with ASD and co-occurring ID (adjusted hazard ratio, 2.89; 95% CI, 2.62–3.17). In conclusion, adults with ASD under the age of 65 were approximately 2.6 times more likely to be diagnosed with dementia compared to the general population in our study.

Rhodus, E.K., Barber, J., Abner, E.L., Bardach, S.H., Gibson, A., & Jicha, G.A.

Aging and Mental Health, 2020, Nov 23;1-9. https://doi.org/10.1080/13607863.2020.1849025

 

Abstract: Similarities exist in behavioral expression of autism spectrum disorder (ASD) and Alzheimer’s disease and related dementias (ADRD). The purpose of this study was to assess presence of behavioral and psychiatric symptoms of dementia (BPSD) and ASD-like behaviors in adults with ADRD. Using a cross-sectional design, data from University of Kentucky Alzheimer’s Disease Center participant cohort were used. Hierarchical linear regression was used to assess (1) the relationship between ASD-like behaviors (measured by the Gilliam Autism Rating Scale-Second Edition, GARS-2) and BPSD measured by the Neuropsychiatric Inventory (NPI), and (2) the relationship between ASD-like behaviors and dementia severity (measured by the Clinical Dementia Rating [CDR] sum of boxes), when controlling for BPSD. Complete data were available for 142 participants. Using α of 0.05, analyses identified ASD behaviors were significantly associated with BPSD severity ratings (r = 0.47; p < 0.001) and dementia severity (r = 0.46; p < 0.001). GARS-2 explained 6.1% (p < 0.001) of variance in CDR sum of boxes when controlling for NPI and other covariates. There is significant overlap in behaviors characteristic of ASD and BPSD as assessed by the NPI and GARS-2, despite the use of these instruments in disparate developmental vs. aging settings. ASD behaviors appear to not be solely present in early childhood as a manifestation of ASD but are also present in older adults with neurodegenerative cognitive impairment. Such associations warrant additional research into causation, assessment, and behavioral interventions to further enable new therapeutic approaches targeting ASD behaviors across the lifespan.

Daniel A. Rossignol, & Richard E. Frye.

Front Pediatr, 2014, 2:87,1-8.  Published online 2014 Aug 22. doi: 10.3389/fped.2014.00087

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Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 1 in 68 children in the United States. Even though it is a common disorder, only two medications (risperidone and aripiprazole) are approved by the U.S. Food and Drug Administration (FDA) to treat symptoms associated with ASD. However, these medications are approved to treat irritability, which is not a core symptom of ASD. A number of novel medications, which have not been approved by the FDA to treat ASD have been used off-label in some studies to treat ASD symptoms, including medications approved for Alzheimer’s disease. Interestingly, some of these studies are high-quality, double-blind, placebo-controlled (DBPC) studies. This article systematically reviews studies published through April, 2014, which examined the use of Alzheimer’s medications in ASD, including donepezil (seven studies, two were DBPC, five out of seven reported improvements), galantamine (four studies, two were DBPC, all reported improvements), rivastigmine (one study reporting improvements), tacrine (one study reporting improvements), and memantine (nine studies, one was DBPC, eight reported improvements). An evidence-based scale was used to rank each medication. Collectively, these studies reported improvements in expressive language and communication, receptive language, social interaction, irritability, hyperactivity, attention, eye contact, emotional lability, repetitive or self-stimulatory behaviors, motor planning, disruptive behaviors, obsessive–compulsive symptoms, lethargy, overall ASD behaviors, and increased REM sleep. Reported side effects are reviewed and include irritability, gastrointestinal problems, verbal or behavioral regression, headaches, irritability, rash, tremor, sedation, vomiting, and speech problems. Both galantamine and memantine had sufficient evidence ranking for improving both core and associated symptoms of ASD. Given the lack of medications approved to treat ASD, further studies on novel medications, including Alzheimer’s disease medications, are needed.

David Toloza Ramírez, Carolina Iturra Pedreros, & Grisol Iturra Pedreros

Revista Ecuatoriana de Neurología, 2020, 29(2), 92-102.  doi:10.46997/revecuatneurol29200092

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Abstract: Autism Spectrum Disorder (ASD) has been studied mainly in children. However, currently, 1/68 adults live with this neurodevelopmental disorder. ASD in adulthood shows suggestive symptoms of cognitive impairment, quickly compromising various cognitive functions. Cognitive impairment and behavioral disorders help to develop neurodegenerative diseases such as Frontotemporal dementia (FTD) and Alzheimer’s Disease (AD) in people with ASD during adulthood, which affects activities of daily living (ADL). The objective of this systematic review is to investigate the progression of ASD to cognitive impairment and dementia in adulthood. The methodology included the qualitative analysis of studies published in the years 2000 and 2020, exclusively in English. Results reveal that adults with ASD develop early cognitive impairment and dementia according to the general population, mainly affecting cognitive functions such as memory and executive functions. In conclusion, moderate to a profound degree of intellectual disability, as well as reductions in white matter, seems to be precursors for the development of cognitive impairment and dementia in adults with ASD. 

Piven, J., & Rabins, P., on behalf of the Autism-in-Older Adults Working Group

J Am Geriatr Soc, 2011, 59, 2151–2155.  doi: 10.1111/j.1532-5415.2011.03632.x

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Abstract: Autism spectrum disorders (ASDs) are among the most common of the severe developmental disabilities, yet little is known about older adults with ASDs—in particular, how the disabilities and dependencies that result from aging interact with those resulting from ASDs. The aging of the population in Western countries, the increasing rate of diagnosis of ASDs, and the burgeoning use of services for ASDs are converging to create a large, growing influx of older adults with ASDs that could impose tremendous humanistic and economic burdens on the healthcare system and society. An understanding of the epidemiological, biological, psychological, and social aspects of ASDs in older adults is essential for preparing to meet their needs, but studies on ASDs in these individuals are practically nonexistent. This article outlines observations and recommendations of a multidisciplinary expert group convened in March 2010 to characterize gaps in knowledge regarding ASDs in older adults and defines research directions to help individuals, the healthcare system, and society prepare for meeting the needs of this population. The proposed research agenda could help improve the lives of older adults with ASDs and inform research and clinical practice involving younger individuals with ASDs.

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"Specific associations with dementia and tremor or ataxia have been demonstrated with aging in individuals with Down syndrome and fragile X syndrome, genetically defined developmental disabilities that are often associated with the presence of autism or autistic features."

Jicha, G.A.
Journal of Alzheimers Disease and Parkinsonism, 2013 Sept, 3:4 [Preceedings of the 2013 International Conference on Psychology, Autism and Alzheimers Disease; San Antonio, Texas].   DOI: 10.4172/2161-0460.S1.004

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Abstract:  Autism spectrum disorders (ASD) represent a heterogeneous cluster of clinical phenotypes that may vary in age of onset, but are classically diagnosed by adolescence or early adulthood at latest. The possibility that development of late life ASD may occur after this age has been poorly explored. Several recent studies have suggested that late life onset of ASD symptoms can develop in frontotemporal dementia, but otherwise have not been linked to the development of neurodegenerative disorders such as Alzheimer?s disease (AD) or mild cognitive impairment (MCI). In order to more fully characterize the possibility of late life emergence of ASD symptoms in MCI and AD, we surveyed the caregivers of 140 subjects with late-life cognitive impairment from the University of Kentucky Alzheimer?s Disease Center Longitudinal Cohort using the GARS-II. Eighty-one caregivers returned the survey for a response rate of 58%. For subjects whose age of onset of cognitive decline was known, autism index ratings based on the sum of the three GARS-II subscale standard scores were associated with age at onset. Subjects with the highest index ratings (Possible/Very likely, n=14) reported significantly (statistically and clinically) younger age at onset than those who scored in the ?Unlikely? range (n=49): 68.2?9.3 vs. 74.9?7.9 (p=0.0088). This remains true when only the dementia cases are considered: 67.7?9.4 (Possible/Very likely, n=13) vs. 74.0?8.8 (Unlikely, n=33): (p=0.038). These data demonstrate that ASD symptoms are seen in conjunction with late-life degenerative dementia of all types and are more prevalent in those with early vs. late onset dementia. It is possible that lifelong subclinical ASD tendencies, might manifest only when neurological function is compromised by the development of even the mildest of pathologic insults in geriatric years. Further work elucidating a potentially complex interplay between ASD and late life dementia could shed much light on our appreciation of preclinical forms of ASD, identify key areas of shared neuroanatomic involvement between ASD and late life dementias, and further provide valuable insights that might hasten the development of therapeutic strategies for both ASD and late life neurodegenerative disorders.

Ian Fyfe

Nat Rev Neurol. 2021 Oct;17(10):595. doi: 10.1038/s41582-021-00564-y.

 

Autism spectrum disorder (ASD) is associated with an increased risk of early-onset dementia, new research has shown. Vivanti et al. used US medical insurance records for >1.2 million individuals aged 30–64 years to examine the prevalence of dementia over 5 years among people with a diagnosis of ASD, ASD with intellectual disability, intellectual disability alone or neither. The prevalence was highest among people with intellectual disability alone (7.10%), but was also considerably higher among people with ASD (4.04%) and people with ASD and intellectual disability (5.22%) than among the healthy population (0.97%). More research will be needed to understand the mechanisms that underlie this association.

Giorgio G. Fumagalli, Alessandro Crippa

Autism. 2016 Jul;20(5):515-516. doi: 10.1177/1362361316647224. Epub 2016 May 2.

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As the prevalence rates of autism and neurodegenerative dementia are rising, it has become a public health priority understanding the factors that might contribute to the co-occurrence of the two conditions. To date, the literature about the intersection between autism and neurodegenerative dementia is still limited although growing. In this perspective article, we summarized the evidence on this topic, describing the behavioral features shared by autism and neurodegenerative dementia, including social communication difficulties, cognitive alterations, and emotional problems. In addition, we reviewed the results from recent studies on the prevalence of dementia in autistic older individuals. Last, we focused on possible shared mechanisms and pathological underpinnings for each condition. We highlighted the importance of understanding the strengths and the needs of autistic subjects who present comorbid dementia, in order to develop long term care resources and arrange appropriate intervention programs. Furthermore, we argued that the systematic study of potentially common etiopathological mechanisms could increase our knowledge about the pathological basis of autism and neurodegenerative dementia, to possibly develop targeted interventions.

Crawford, D., Abner, E., Glaser, P., & Jicha, G.
Neurology, Apr 2014, 82 (10 Supplement) I4-1.009.  https://n.neurology.org/content/82/10_Supplement/I4-1.009

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Evaluate the presence of autistic symptoms in a geriatric cohort with mild cognitive impairment and early dementia. Autistic spectrum disorders (ASD) vary in age of onset, but are classically diagnosed by adolescence or early adulthood at latest. The possibility that development of late life ASD may occur has been poorly explored. Recent studies have suggested that late life onset of ASD symptoms can develop in frontotemporal dementia, but have not been linked to the development of other dementias or mild cognitive impairment (MCI). In order to characterize late- life ASD symptoms in MCI and dementia, we surveyed the caregivers of 140 subjects with late-life cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the GARS-II. Eighty-one subjects returned the survey for a response rate of 58%. Subjects with the highest autism index ratings reported significantly younger age at onset of decline than those who scored in the ‘Unlikely’ range (n=49): 68.2±9.3 vs 74.9±7.9 (p < 0.01). This remains true when the respondents were restricted to just those cases with dementia (n=13 and n=33): 67.7±9.4 vs. 74.0±8.8 (p < 0.05). These data demonstrate that ASD symptoms are associated with late-life degenerative dementia and that such symptoms are more prevalent in those with early vs. late onset dementia. It is possible that lifelong subclinical ASD tendencies, might manifest only when neurological function is compromised by the development of even the mildest of pathologic insults in geriatric years. Further work examining the interplay between ASD and late life dementia could help identify key areas of shared neuroanatomic involvement between ASD and late life dementias, and provide valuable insights that might hasten the development of therapeutic strategies for both ASD and behavioral features seen in MCI and dementia states.

Roestorf, A., Howlin, P., & Bowler, D.M.
Frontiers in Psychology, 2022 Aug. https://doi.org/10.3389/fpsyg.2022.741213

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Poor mental health is known to adversely affect functional abilities, social isolation, and quality of life (QoL). It is, therefore, crucial to consider the long-term impacts of mental health conditions as autistic adults grow older. To explore, in a group of community-based autistic adults, the extent of: (i) autistic traits, co-occurring physical and mental health conditions; (ii) age-related differences in those conditions, and changes over time; and (iii) their impact on everyday living and QoL. About Sixty-eight autistic adults (aged 19–80 years) participated in the first study (T1); 49 participants from T1 took part in a follow-up at T2 (mean retest interval 2.4 years). Standardised self-report measures of autistic traits, mental health, and QoL were completed at both time points. Over two-thirds (71%) of autistic adult participants experienced at least one co-occurring condition, and over a third (37%) met the criteria for three or more co-occurring conditions. Mental and physical health difficulties were related to autistic traits and difficulties in everyday life and were consistent predictors of poor QoL at T1 and T2. Mental health difficulties in autism persisted into older age and did not improve over time. These findings have important implications for mental health provision for autistic adults in older age.

Jicha, G.A.
Journal of Alzheimers Disease and Parkinsonism, 2013 Sept, 3:4 [Preceedings of the 2013 International Conference on Psychology, Autism and Alzheimers Disease; San Antonio, Texas].   DOI: 10.4172/2161-0460.S1.004

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Autism spectrum disorders (ASD) represent a heterogeneous cluster of clinical phenotypes that may vary in age of onset, but are classically diagnosed by adolescence or early adulthood at latest. The possibility that development of late life ASD may occur after this age has been poorly explored. Several recent studies have suggested that late life onset of ASD symptoms can develop in frontotemporal dementia, but otherwise have not been linked to the development of neurodegenerative disorders such as Alzheimer?s disease (AD) or mild cognitive impairment (MCI). In order to more fully characterize the possibility of late life emergence of ASD symptoms in MCI and AD, we surveyed the caregivers of 140 subjects with late-life cognitive impairment from the University of Kentucky Alzheimer?s Disease Center Longitudinal Cohort using the GARS-II. Eighty-one caregivers returned the survey for a response rate of 58%. For subjects whose age of onset of cognitive decline was known, autism index ratings based on the sum of the three GARS-II subscale standard scores were associated with age at onset. Subjects with the highest index ratings (Possible/Very likely, n=14) reported significantly (statistically and clinically) younger age at onset than those who scored in the ?Unlikely? range (n=49): 68.2?9.3 vs. 74.9?7.9 (p=0.0088). This remains true when only the dementia cases are considered: 67.7?9.4 (Possible/Very likely, n=13) vs. 74.0?8.8 (Unlikely, n=33): (p=0.038). These data demonstrate that ASD symptoms are seen in conjunction with late-life degenerative dementia of all types and are more prevalent in those with early vs. late onset dementia. It is possible that lifelong subclinical ASD tendencies, might manifest only when neurological function is compromised by the development of even the mildest of pathologic insults in geriatric years. Further work elucidating a potentially complex interplay between ASD and late life dementia could shed much light on our appreciation of preclinical forms of ASD, identify key areas of shared neuroanatomic involvement between ASD and late life dementias, and further provide valuable insights that might hasten the development of therapeutic strategies for both ASD and late life neurodegenerative disorders.

Janicki, M.P.,J.A, Hendrix, McCallion, P., and the Neuroatypical Conditions Expert Consultative Panel

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2022, 14(1), e12335.  https://doi.org/10.1002/dad2.12335

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Abstract: The Neuroatypical Conditions Expert Consultative Panel composed of numerous clinical and academic experts was convened to examine barriers to the examination of cognitive impairment in adults with a variety of neuroatypical conditions. Neuroatypical conditions affect normative intellectual development and function (such as intellectual disability and intellectual disability with conjoint psychiatric conditions), thought, moods, and cognition (such as severe mental illness), communication functions (such as the autism spectrum and hearing/vision impairments), and brain and motor function (such as cerebral palsy and acquired or traumatic brain injury). The panel concluded that current federal guidance for the assessment of cognitive impairment for mild cognitive impairment (MCI) or dementia does not sufficiently include information as to how to assess such adults. In addition, it concluded that adults with these conditions (1) challenge clinicians when attempting to discern current behavior and function from that which was pre-existing; (2) often have inherent comprehension and oral communication difficulties, motor task performance impediments, and difficulty with visuals; and (3) pose difficulties when assessed with standardized dementia measures and can benefit from the use of specialized instruments. The panel recommended that federal guidance be broadened to include adaptations of assessment practices to accommodate neuroatypical conditions; that educational packs be developed for clinicians about such conditions and on detecting and diagnosing MCI or dementia; and that research be expanded to produce more evidence-based information on both assessing adults with neuroatypical conditions for later-life adult cognitive diseases/disorders and planning post-diagnostic care.

Michael, C.

Autism, 2016 Jul;20(5):515-6. doi: 10.1177/1362361316647224. Epub 2016 May 2.

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Abstract: Neurotypical adults and their families aspire to a high standard of care as they grow older. The knowledge that this care is available, supported by research, and monitored and delivered by trained professionals provides reassurance. Autistic people are entitled to the same level of support as other people, but structures to ensure this support do not exist outside of policy documents and some rare centers of excellence. Many of us, autistic people, wonder how our old age will look like, and we do not have answers. Knowing there is such a paucity of research about supporting us as we grow older makes old age a frightening prospect. Research into any lifelong condition usually follows the lifespan of individuals with that condition as a way of understanding its trajectory and to provide a point of reference against which the success of interventions can be marked. Yet, with only a few exceptions, autism research has generally excluded autistic people over the age of 40 years . We know virtually nothing about what happens to autistic people, physically, cognitively, emotionally and socially as we pass through middle and older age. What we do know is that there is a much greater risk of premature mortality in autism; on average, autistic people with additional intellectual disability die 30 years before non-autistic people  – with epilepsy identified as the biggest cause of premature death in this group – and those autistic people without an intellectual disability die 12 years earlier than typical adults. Why invest resources in researching autism interventions in earlier years and then ignore their long-term outcomes or monitor the trajectory of autistic lives to their conclusion? Cognitive changes and various neurological conditions are important areas of research not only for how they affect autistic people but also for how they may manifest differently than in ageing neurotypical people. There is a theory that autistic people may cope better with or be protected against the effects of cognitive ageing, which, if true, could inform dementia research in the general population.

Klein, C.B., McQuaid, G.A., Charlton, R.A., Klinger, L.G., & Wallace, G.L.

Autism Res. 2022 Dec 13. doi: 10.1002/aur.2877. Epub ahead of print. PMID: 36513614.

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Abstract: Very little is known about autistic adults as they age. Early evidence suggests a potentially high risk for dementia and atypical cognitive decline in autistic middle and older age adults. Research in the general population indicates that self-reported cognitive decline may predict future dementia earlier than performance-based measures. Nevertheless, self-report dementia screeners have not been used to date in autism research. In a sample of middle and older age autistic adults (N = 210), participants completed a self-rated dementia screener, the AD8, to describe the rate of cognitive decline, examine associations of cognitive decline with age, educational level, sex designated at birth, and autistic traits, and document the psychometrics of a dementia screener in autistic adults. We found high rates of cognitive decline with 30% of the sample screening positive. The most common symptoms were declining interest in leisure activities, and increases in everyday problems with thinking, memory, and judgment. There was evidence that autistic individuals designated female at birth may be more vulnerable to cognitive decline than autistic individuals designated male at birth. Notably, reports of cognitive decline did not vary by age or educational level. Modestly elevated autistic traits were found in those screening positive versus negative for cognitive decline. Finally, the dementia screener showed good psychometrics, including convergent validity with an independent measure of current memory problems. These results could signal an emerging public health crisis in autistic adults as they age, and support the potential utility of self-report measures for early screening for cognitive decline in this population.

Fumagalli, G.G., & Crippa, A.

Minerva Psychiatry, 2022 September, 63(3), 189-196. DOI: 10.23736/S2724-6612.22.02370-3

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Abstract: As the prevalence rates of autism and neurodegenerative dementia are rising, it has become a public health priority understanding the factors that might contribute to the co-occurrence of the two conditions. To date, the literature about the intersection between autism and neurodegenerative dementia is still limited although growing. In this perspective article, we summarized the evidence on this topic, describing the behavioral features shared by autism and neurodegenerative dementia, including social communication difficulties, cognitive alterations, and emotional problems. In addition, we reviewed the results from recent studies on the prevalence of dementia in autistic older individuals. Last, we focused on possible shared mechanisms and pathological underpinnings for each condition. We highlighted the importance of understanding the strengths and the needs of autistic subjects who present comorbid dementia, in order to develop long term care resources and arrange appropriate intervention programs. Furthermore, we argued that the systematic study of potentially common etiopathological mechanisms could increase our knowledge about the pathological basis of autism and neurodegenerative dementia, to possibly develop targeted interventions.

Happé, F., & Charlton, R.A.

Gerontology, 2012, 58(1), 70-78. doi: 10.1159/000329720. Epub 2011 Aug 24. PMID: 21865667.

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Abstract: This article addresses an important and barely researched topic: what happens to children with autism spectrum disorders when they grow old. We review the small published literature on aging in autism. We then consider the relevance of research on ‘neurotypical’ aging in core domains of autistic impairment: social cognition, executive function, cognitive style and memory. Research themes from the study of normal aging, including cognitive reserve, compensation, quality of life, loneliness and physical health are of relevance for future research on autism. Studies of aging in autism will be important not only to plan appropriate services, but also to shed light on the full developmental trajectory of this neurodevelopmental condition, and perhaps provide clues to neuropathology and etiology.

Perkins, E.A., & Berkman, K,A.

Am J Intellect Dev Disabil, 2012 Nov,117(6), 478-96. doi: 10.1352/1944-7558-117.6.478. PMID: 23167487

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Abstract: Research investigation of older adults with autism spectrum disorders (ASD) noticeably lags behind studies of children and younger adults with ASD. This article reviews the current literature regarding a range of quality of life outcomes of aging adults with ASD. Studies that have addressed life expectancy, comorbid physical and mental health issues, ASD symptomatology, and social, residential, and vocational outcomes are reviewed. Research challenges in identifying older cohorts of adults with ASD are also discussed, and notable areas of concern are highlighted. Overall, aging with ASD does present challenges, but there is also evidence that positive outcomes are attainable. The article concludes with brief recommendations on how to optimize the aging process for individuals with ASD.

Rhodus, E.K., Barber, J., Kryscio, R.J. et al.

J Neurol., 269, 5105–5113 (2022). https://doi.org/10.1007/s00415-022-11167-y

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Abstract: The pathologic substrates or neuroanatomic regions responsible for similarities in behavioral features seen in autism spectrum disorder and late-life dementia remain unknown. The present study examined the neuropathologic features of late-life dementia in research volunteers with and without antemortem behaviors characteristic of autism spectrum disorders. Antemortem cross-sectional assessment of autistic spectrum behaviors proximal to death in persons with diagnosis of mild cognitive impairment or dementia was completed using the Gilliam Autism Rating Scale, 2nd edition (GARS-2), followed by postmortem quantitative and semiquantitative neuropathologic assessment. All individuals who completed the GARS-2 prior to autopsy were included (n = 56) and we note that no participants had known diagnosis of autism spectrum disorder. The GARS-2 was used as an antemortem screening tool to stratify participants into two groups: “Autism Possible/Very Likely” or “Autism Unlikely.” Data were analyzed using nonparametric statistics comparing location and scale to evaluate between-group differences in pathologic features.  Neurofibrillary tangles (NFT; p = 0.028) density and tau burden (p = 0.032) in the frontal region, the NFT density (p = 0.048) and neuritic plaque burden (p = 0.042), and the tau burden (p = 0.032) of the temporal region, were significantly different in scale between groups. For measures with significant group differences, the medians of the Autism Possible/Very Likely group were roughly equal to the 75th percentile of the Autism Unlikely group (i.e., the distributions were shifted to the right). This study links behaviors characteristic of autism to increased pathologic tau burden in the frontal and temporal lobes in persons with late-life dementia. Additional studies are needed to determine causal factors and treatment options for behaviors characteristic of autism behaviors in late-life dementias.

Liu S, Larsson H, Kuja-Halkola R, Lichtenstein P, Butwicka A, Taylor MJ.

Lancet Healthy Longev. 2023 Jul;4(7):e307-e315. doi: 10.1016/S2666-7568(23)00067-3. Epub 2023 Jun 6. PMID: 37295448.

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Abstract: Research of health outcomes in older autistic adults (≥45 years) is concerningly scarce, and little is known about whether intellectual disability and sex affect the health outcomes of this population. The aim of this study was to investigate the association between autism and physical health conditions in older adults and to examine these associations by intellectual disability and sex. Authors conducted a longitudinal, retrospective, population-based cohort study of the Swedish population born between Jan 1, 1932, and Dec 31, 1967, using linked data from the nationwide Total Population Register and the National Patient Register. They excluded individuals who died or emigrated before the age of 45 years, or with any chromosomal abnormalities. Follow-up started at age 45 years for all individuals, and ended at emigration, death, or Dec 31, 2013 (the latest date of available follow-up), whichever was soonest. Diagnoses of autism, intellectual disability, 39 age-related physical conditions, and five types of injury (outcomes) were obtained from the National Patient Register. For each outcome, they calculated 25-year cumulative incidence and used Cox models to estimate hazard ratios (HRs). All analyses were repeated separately by intellectual disability and sex. Findings Of 4200887 older adults (2063718 women [49·1%] and 2137169 men [50·9%]) in the study cohort, 5291 (0·1%) had a diagnosis of autism recorded in the National Patient Register. Older autistic adults (median follow-up 8·4 years [IQR 4·2–14·6]) had higher cumulative incidence and HRs of various physical conditions and injuries than their non-autistic counterparts (median follow-up 16·4 years [8·2–24·4]). In autistic individuals, the highest cumulative incidence was observed for bodily injuries (50·0% [95% CI 47·6–52·4]). Conditions that autistic adults were at higher risk of than were non-autistic adults included heart failure (HR 1·89 [95% CI 1·61–2·22]), cystitis (2·03 [1·66–2·49]), glucose dysregulation (2·96 [2·04–4·29]), iron deficiency anemia (3·12 [2·65–3·68]), poisoning (4·63 [4·13–5·18]), and self-harm (7·08 [6·24–8·03]). These increased risks mainly persisted regardless of intellectual disability or sex. Their data indicate that older autistic adults are at substantially increased risk of age-related physical conditions and injuries compared with non-autistic adults. These findings highlight the need for collaborative efforts from researchers, health services, and policy makers to provide older autistic individuals with the necessary support to attain healthy longevity and a high quality of life.

Geurts, H. M., & Vissers, M. E.

Journal of Autism and Developmental Disorders, 2012, 42(5), 665–675. https://doi.org/10.1007/s10803-011-1291-0

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Abstract: Cognitive autism research is mainly focusing on children and young adults even though we know that autism is a life-long disorder and that healthy aging already has a strong impact on cognitive functioning. We compared the neuropsychological profile of 23 individuals with autism and 23 healthy controls (age range 51–83 years). Deficits were observed in attention, working memory, and fluency. Aging had a smaller impact on fluency in the high functioning autism (HFA) group than in the control group, while aging had a more profound effect on visual memory performance in the HFA group. Hence, we provide novel evidence that elderly with HFA have subtle neuropsychological deficits and that the developmental trajectories differ between elderly with and without HFA in particular cognitive domains..

Torenvliet, C., Groenman, A.P., Radhoe, T.A., Agelink van Rentergem, J.A., Van der Putten, W.J., & Geurts, H.M.

Psychiatry Research, 2023, 321,115063. https://doi.org/10.1016/j.psychres.2023.115063.

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Abstract: Longitudinal studies on cognitive aging in autism are scarce, and largely underpowered, yet essential to obtain more conclusive results on cognitive changes in autism during adulthood. In the largest longitudinal study on cognition thus far, we aimed to get more insight into cognitive aging in autism. As pre-registered, we computed reliable change indices (RCIs) and multilevel models to estimate cognitive changes in 128 autistic, and 112 non-autistic adults (range: 24–85 yrs.) over two to three timepoints (average interval: 3.5 yrs.). Participants were tested on 15 outcome measures, covering verbal memory, visual (working) memory, prospective memory, theory of mind, fluency, response speed, inhibition, planning, and switching. RCIs showed no significant differences between groups (autism/no-autism) in changes over time. Using multilevel models, most tasks showed sensitivity to cross-sectional age-related effects, and/or longitudinal changes, with worse performance at older age, and later timepoints. However, effects were not significantly different between the autism and no-autism group. This lack of group differences was substantiated by additional Bayesian analyses. In sum, the current study provides evidence for parallel (similar) cognitive aging in autism. Specifically, autistic individuals diagnosed in adulthood, without intellectual disability, do not seem at risk for accelerated cognitive decline.

van Niekerk MEH, Groen W, Vissers CTWM, van Driel-de Jong D, Kan CC, Oude Voshaar RC.

International Psychogeriatrics. 2011;23(5):700-710. doi:10.1017/S1041610210002152

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Abstract:  As autism spectrum disorders (ASD) have largely been neglected in old-age psychiatry, the objective of the present paper is to describe the diagnostic process in elderly patients. A systematic review of the literature on ASD in older age was undertaken and illustrated by a case series of three elderly patients first diagnosed with ASD in later life by a tertiary mental health clinic. The search of the literature only yielded three papers on late-life ASD, while the review of the available diagnostic procedures among adults suggests some relevance for screening instruments (Autism Questionnaire), diagnostic instruments (Module 4, Autism Diagnostic Observation Schedule), and neuropsychological examination to profile impairments. Nonetheless, the case reports clearly showed that taking a thorough history with the patient, corroborated and supplemented by a close relative or caregiver who has known the patient for at least ten years, still remains the most important diagnostic tool. The three case studies show that in clinical practice ASD can easily be missed in elderly individuals presenting with comorbid psychiatric disorders, potentially causing iatrogenic damage. Although further research on phenotyping and diagnosing ASD in older people is warranted, the most important step at this point is to create a greater awareness of the possibility of ASD in old age among health-care professionals working with people in this age group.

Nylander L, Gillberg C.

Acta Psychiatr Scand. 2001 Jun;103(6):428-34. doi: 10.1034/j.1600-0447.2001.00175.x.

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Abstract:  To estimate the prevalence of autism spectrum disorders (ASD) among adult psychiatric out-patients; to evaluate the efficacy of a new brief screening questionnaire (ASDASQ). 1323 adult psychiatric out-patients were screened by staff. Analysis of psychiatric records of patients (n = 66) scoring high on the ASDASQ yielded 31 patients with a suspected ASD. Twenty-two of these patients were clinically examined. Three psychometric aspects of the questionnaire were studied. Seventeen patients were found by clinical examination to have an ASD. Since two patients scoring low on the ASDASQ were known to have an ASD, at least 19 patients in this population (1.4%) had a definite ASD. Seventeen of the ASD patients had been previously diagnosed with other psychiatric disorders, most frequently schizophrenia (n = 5). Of patients attending a treatment centre for severe psychiatric disabilities (n = 499), 3.2% had an ASD. The ASDASQ showed good reliability across and within raters. Internal consistency was excellent. Adult psychiatric patients sometimes have undiagnosed autism spectrum disorders. The ASDASQ can be useful for screening.

Hayes, J., Ford, T., Rafeeque, H. et al.

BMC Psychiatry 18, 222 (2018). https://doi.org/10.1186/s12888-018-1800-1

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Abstract:  Research suggests that diagnostic procedures for Autism Spectrum Disorder are not consistent across practice and that diagnostic rates can be affected by contextual and social drivers. The purpose of this review was to consider how the content of clinical practice guidelines shapes diagnoses of Autism Spectrum Disorder in the UK; and investigate where, within those guidelines, social factors and influences are considered. We electronically searched multiple databases (NICE Evidence Base; TRIP; Social Policy and Practice; US National Guidelines Clearinghouse; HMIC; The Cochrane Library; Embase; Global health; Ovid; PsychARTICLES; PsychINFO) and relevant web sources (government, professional and regional NHS websites) for clinical practice guidelines. We extracted details of key diagnostic elements such as assessment process and diagnostic tools. A qualitative narrative analysis was conducted to identify social factors and influences. Twenty-one documents were found and analyzed. Guidelines varied in recommendations for use of diagnostic tools and assessment procedures. Although multidisciplinary assessment was identified as the ‘ideal’ assessment, some guidelines suggested in practice one experienced healthcare professional was sufficient. Social factors in operational, interactional and contextual areas added complexity to guidelines but there were few concrete recommendations as to how these factors should be operationalized for best diagnostic outcomes. Although individual guidelines appeared to present a coherent and systematic assessment process, they varied enough in their recommendations to make the choices available to healthcare professionals particularly complex and confusing. We recommend a more explicit acknowledgement of social factors in clinical practice guidelines with advice about how they should be managed and operationalized to enable more consistency of practice and transparency for those coming for diagnosis.