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Overlaps in biological pathways, clinical features and behavioural expression
Although Alzheimer’s disease (AD) and ASD are etiologically distinct conditions, there is growing evidence of significant overlaps in biological and neurological features, and behavioural expression of ASD and AD (and related dementias). Studies also suggest that there are common neurological pathways in both ASD and dementia, particularly involving the immune system and synaptic signaling. A genetic convergence has been proposed as well.
Emerging research has begun to explore the complex relationship between ASD and dementias, offering new insights into potential therapies and support strategies for managing co-occurring conditions.
Behaviours
ASD behaviours that are present in early childhood as a manifestation of ASD are also present in older adults with neurodegenerative cognitive impairment (Rhodus et al. 2020). Both conditions involve challenges with social interaction, language impairment, executive functions, memory deficits and motor problems (Khan et al. 2016); insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments (Nadeem et al. 2021).
Some clinical studies have described autism spectrum-like behaviours in approximately 16% of late-onset dementia cases. The research studies by Rhodus et al. (2022) link behaviours characteristic of autism to increased pathologic tau [protein] burden in the frontal and temporal lobes in persons with late-life dementia. Yet, the present data demonstrate that frontotemporal lobar degeneration pathology is not a major contributor to such behaviours in a community-based cohort of late-life dementia.
Rhodus et al. (2020) compared behaviours characteristic of ASD and behavioural and psychiatric symptoms of dementia. The researchers suggest that ASD behaviours may seem de novo of degenerative dementia and such behaviours are more prevalent in those with early onset dementia. Autistic individuals demonstrated significantly (statistically and clinically) younger age at the onset of cognitive impairment and AD than those without autism.
Having evaluated the presence of autistic symptoms in people with mild cognitive impairment and early dementia, Crawford et al. (2014) suggest 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). They 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.
Stereotypical movements are characteristic of autism but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). The FTD patients with stereotypical movements (such as, e.g., frequent rubbing behaviours) and self-injurious acts also manifest compulsive-like behaviours, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor (Mendez et al. 2005).
The existence of the behavioural variant of frontotemporal dementia (bv-FTD), including senile Asperger’s syndrome (AS), has been proposed. Midorikawa & Kawamura (2012) present three patients who showed symptoms of bv-FTD and demonstrated signs of ASD, especially Asperger Syndrome. They also compared these data with those obtained from three individuals with Alzheimer’s disease. All three patients met the criteria for bv-FTD and had a higher Autism-Spectrum Quotient score than did comparable AD people. The researchers conclude that it is possible that some senile persons with frontotemporal lobar degeneration-like maladaptive behaviour may also have subclinical Asperger Syndrome.
Sakuta et al. (2021) investigated the symptomatic similarity of semantic dementia (SD) and ASD. The SD group showed high prevalence in four behaviours related to stereotypy and social impairment: eating very few food items, selfishness, difficulty in recognizing others' feelings and thoughts, and interpreting language literally.
Behavioural inflexibility is a symptom of certain conditions, such as OCD, ASD and AD. Recent evidence suggests that insulin, which is usually known for helping our bodies use sugar, also helps our brains control our behaviour. When people have trouble using insulin, they might become anxious and keep doing the same thing over and over again. Sullivan et al. (2023) explore the circuitry underlying behavioural flexibility, changes in Type 2 diabetes, the role of insulin in central nervous system (CNS) outcomes and mechanisms of insulin involvement across disorders of behavioural inflexibility. The researchers have found that metformin, which is used to treat Type 2 diabetes, can help with some of these brain disorders.
Shared Biological Pathways between ASD and Dementias
The shared pathways between ASD and dementias suggest that understanding one condition may be helpful in understanding the other.
Genetic and Epigenetic genetic overlapping between ASD and Dementia
Studies have found shared genetic and epigenetic markers that may contribute to the development of both ASD and dementias. A number of certain susceptible genes and proteins link both conditions, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1 (Nadeem et al. 2021) However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation (Nadeem et al. 2021).
They also found that 14 genes that control synaptic and inflammatory pathways exhibited age-dependent differences between the brains of those with autism and controls (Harris 2023). Initial excess and overconnectivity of neurons may make the brains of autistic individuals more vulnerable to early aging and inflammation, which may lead to further changes in the brain structure and function (Schumann 2023).
The activity-dependent neuroprotective protein (ADNP) gene is especially important because it's linked to autism, intellectual disabilities, and Alzheimer's disease. (If intact, ADNP protects against AD-tauopathy.) But when it's mutated, it can cause problems (ASD, intellectual disabilities and AD) (Ivashko-Pachima et al. 2021).
This genetic basis makes the background of common associations like memory deficits, cognition changes, language impairments, DNA methylation, demyelination, oxidative stress and inflammation, an integral part of both conditions. According to Khan et al. (2016), 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. 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 (Khan et al. 2016).
The Role of Inflammation and Oxidative Stress
Recent research has identified inflammation and oxidative stress as shared pathways in both ASD and dementia. Inflammation, in particular, has been implicated in the development and progression of both conditions. The researchers analysed brain tissue from a region of the brain involved in language processing and social perception. Some changes in the brains of autistic people overlapped significantly with changes reported in people with Alzheimer’s disease (Harris 2023; Nadeem et al. 2021).
The cerebral vasculature
Although neurodevelopmental and neurodegenerative disorders express different clinical features at different stages of life, they share similar vascular abnormalities.
Healthy brain development and aging are both ensured by the anatomical and functional interaction between the vascular and nervous systems that are established during brain development and maintained throughout the lifespan. During critical periods of brain development, vascular networks remodel until they can actively respond to increases in neural activity through neurovascular coupling, which makes the brain particularly vulnerable to neurovascular alterations.
The brain vasculature has been strongly associated with the onset and/or progression of disorders associated with aging, and more recently with neurodevelopmental conditions. Ouellette & Lacoste (2021) present an overview of vascular dysfunctions (the ‘vascular continuum’) associated with neurodevelopmental (ASDs, schizophrenia, Down Syndrome) and neurodegenerative (multiple sclerosis, Huntington’s, Parkinson’s, and Alzheimer’s) conditions, providing the evidence that deficits in angiogenesis, cerebral blood flow and the blood-brain barrier are causally linked to cognitive impairment.
Savant skills
Alzheimer's and other forms of dementia can be debilitating diseases that cause memory loss and cognitive impairment. However, like some individuals with ASD, some people with dementias develop remarkable abilities despite their cognitive decline, known as savant skills.
Alzheimer's and other forms of dementia can be debilitating diseases that cause memory loss and cognitive impairment. However, like some individuals with ASD, some people with dementias develop remarkable abilities despite their cognitive decline, known as savant skills.
Recent studies have shed some light on why some people with Alzheimer's or dementia develop savant abilities. Researchers have discovered that brain damage in certain parts of the brain can cause "release phenomena," where individuals experience a sudden explosion of creative or cognitive ability due to disinhibition of neural pathways. It has been noted that savant skills mostly develop in people who have had a lifetime of exposure or practice in certain areas. For example, a person who has been pianist their entire life and develops Alzheimer's or dementia may suddenly play the piano exceptionally well despite the cognitive impairment. However, music and art skills can emerge in individuals who have never been interested in art or music (Miller et al. 1998).
It is important to note that not everyone with Alzheimer's or dementia will develop savant skills, and the emergence of these skills does not indicate a reversal of cognitive decline. However, the development of savant skills in these individuals is a fascinating and noteworthy phenomenon that can provide insight into the workings of the brain and offer hope to those struggling with these debilitating conditions. Understanding how these skills develop can help researchers develop better treatments and improve the quality of life for those affected by Alzheimer's or dementia.
As the global population ages, there is a growing need for research into the relationship between ASD and dementia. While there is some emerging evidence of overlaps between these conditions, there is still much that is unknown.
Understanding the overlaps between these conditions and the shared pathways will be crucial for developing effective public health policies that address the complex needs of individuals with co-occurring ASD and dementia.
Understanding the shared pathways is essential for developing targeted treatments and interventions that address the underlying mechanisms of both conditions.
Addressing the needs of those with co-occurring ASD and dementia requires a comprehensive and integrated approach to care and development of specialized support programmes for those affected (and their carers).
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