Behaviors Characteristic of Autism Spectrum Disorder in a Geriatric Cohort With Mild Cognitive Impairment or Early Dementia

Abstract

Introduction-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.Methods-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.Results-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.Discussion-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.

Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid

“…It was indicated that more than 10 percent of people diagnosed with autism from age 40 to 60 develop a dementia condition such as AD within 15 years [ 71 ]. Moreover, recent research data in a geriatric cohort with mild cognitive impairment or early dementia demonstrate that ASD behaviours may appear de novo of degenerative dementia and autistic behaviours are more prevalent in those with early-onset dementia [ 72 ]. The same research group indicated a correlation of autism-like behaviours with increased levels of Tau and neurofibrillary pathology in the frontal lobes at autopsy in subjects with late-life dementia [ 73 ].…”

Role of Neuroinflammation in Autism Spectrum Disorder and the Emergence of Brain Histaminergic System. Lessons Also for BPSD?

“…However, it is now widely recognized that there is substantial overlap between the two conditions, based on genetic underpinnings, epidemiological similarities, and the high rates of cooccurrence (Wood, 2017). Interestingly, behavioral characteristics of ASD have been described in individuals with MCI or early dementia, demonstrating the possibility of late-life emergence of behaviors characteristic of ASD as part of MCI or AD (Rhodus et al, 2019) (Table 1). Moreover, the genetic basis of ASD and AD implies common associations like memory deficits, cognition changes, demyelination, oxidative stress and inflammation, a fundamental part of both disorders (Table 1) (Khan et al, 2016).…”

“…During pregnancy, both environmental and genetic risk factors may affect inflammatory response of new-borns, hence altering postnatal brain development (Adams-Chapman and Stoll, 2006). These genetic and environmental factors can directly elicit chronic neuroinflammation which in turn may (Rhodus et al, 2019) Similarities of ASD and BPSD (Rhodus et al, 2019) Common mechanisms of ASD and AD (Khan et al, 2016) -Deficits in social communication and social interaction -Restricted, repetitive patterns of behavior, interests, or activities including repetitive movements, use of objects, or speech -Inflexibility in terms of routines modulate neuronal function and immune response via glia activation, or directly by affecting neuronal function (Depino, 2013) (Figure 2). Valproic acid (VPA), as an environmental risk factor, elicited activation in different brain regions, with evidence of long-lasting glia activation in the hippocampus and the cerebellum (Lucchina and Depino, 2014).…”

“…Interestingly, BPSD are present in almost 90% of patients diagnosed with AD, characterized as a disorder of heterogeneous degenerative symptoms with memory and cognitive deficits considered as the core symptoms across multiple symptom domains (Chakraborty et al, 2019). Many BPSD share similarities with symptoms observed in AD, schizophrenia (SCH), and ASD including depression, anxiety, executive functioning deficits, and communication deficits (Wallace et al, 2016;Rhodus et al, 2019). ASD is a biologically based persistent neurodevelopmental disorder of which the core symptoms include impaired social interaction and repetitive behaviors with restricted interests (Baronio et al, 2015).…”

Deterioro Cognitivo y Demencias en Adultos con Trastorno del Espectro Autista.

“…Del total de los participantes el mayor porcentaje correspondía a sujetos con diagnóstico de EA, ante lo cual los autores concluyeron que el cuadro clínico de TEA se hace evidente en sujetos que cursan con EA a medida que este proceso neurodegenerativo aumenta su severidad en términos de deterioro cognitivo. 91 Estas asociaciones con EA no resultan extrañas, ya que, este tipo de demencia manifiesta no sólo compromiso cognitivo, si no que también sintomatología conductual la cual se porta en sujetos con TEA. 92 En concordancia, diversos autores postulan la existencia de un posible TEA subclínico a lo largo de la vida, el cual se manifiesta sólo cuando el funcionamiento cognitivo se ve comprometido debido a lesiones neurológicas o eventos neurodegenerativos en edad avanzada.…”