Autism and Dementia
Diagnosis, Care, and Follow Up of Dementia in Persons with Intellectual Disabilities and Autism
Serafino Corti and Michela Uberti
Fondazione Instituto Ospedaliero di Sospiro - Onlis
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Neurodevelopmental Conditions and Aging: Report on the Atlanta Study Group Charrette on Neurodevelopmental Conditions and Aging
Matthew P Janicki, C Michael Henderson, I Leslie Rubin,& 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
Alzheimer's Disease and Autistic Spectrum Disorder: Is There Any Association?
Sarah A Khan, Shahida A Khan, A R Narendra, Gohar Mushtaq, Solafa A Zahran, Shahzad Khan, & Mohammad A Kamal
CNS Neurol Disord Drug Targets, 2016;15(4):390-402.
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.
[Developmental Disorders and Dementia] original in Japanese
Brain Nerve, 2015 Sep;67(9):1125-32. doi: 10.11477/mf.1416200271.
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.
Premature Mortality in Autism Spectrum Disorder
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
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.
Exploring Comorbidity Within Mental Disorders Among a Danish National Population
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.
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.
"More than 10 percent of people diagnosed with autism from age 40 to 60 develop a dementia condition such as Alzheimer’s disease within 15 years."
Discovery of Autism/Intellectual Disability Somatic Mutations in Alzheimer's Brains: Mutated ADNP Cytoskeletal Impairments and Repair as a Case Study
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
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.
Autistic Symptoms in a Geriatric Population with Mild Cognitive Impairment and Early Dementia (I4-1.009)
Danielle Crawford, Erin Abner, Paul Glaser, & Gregory Jicha
Neurology, 2014, April 08, 2014; 82 (10 Supplement) https://n.neurology.org/content/82/10_Supplement/I4-1.009
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.
The Relationship between Subclinical Asperger’s Syndrome and Frontotemporal Lobar Degeneration
Midorikawa A. & Kawamura M
Dementia and Geriatric Cognitive Disorders Extra, 2012, 2, 180–186. https://doi.org/10.1159/000338174
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.
Age at Death and Comorbidity of Dementia-related Disorders among Individuals with Autism Spectrum Disorder
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
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.
Autistic Spectrum Behaviors in Late-life Dementia are Associated with an Increased Burden of Neurofibrillary Tangles in the Frontal Lobe
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.
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.
"Older Adults with ASD: The Consequences of Aging." Insights from a Series of Special Interest Group Meetings Held at the International Society for Autism Research 2016-2017
Research in Autism Spectrum Disorders, 2019, Jul; 63, 3-12. doi:10.1016/j.rasd.2018.08.007.
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.
The Physical and Mental Health of Middle Aged and Older Adults on the Autism Spectrum and the Impact of Intellectual Disability
Lauren Bishop-Fitzpatrick, & Eric Rubenstein
Research in Autism Spectrum Disorders, 2019, Jul, 63, 34-41. doi:10.1016/j.rasd.2019.01.001. Epub 2019 Jan 29.
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.
Strategies for Research, Practice, and Policy for Autism in Later Life: A Report from a Think Tank on Aging and Autism
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.