September 29, 2021


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Tags: Autism, conditions, link, neurodegenerative, search, Spectrum


Categories: autism

The seek for a hyperlink between autism and neurodegenerative circumstances | Spectrum

About five years ago, when his younger twin brothers turned thirty, Giacomo Vivanti wondered how the two, both of whom suffer from autism, would fare in middle and old age. In particular, he wondered if they might be prone to developing age-related neurological disorders.

His brothers showed no signs of illness or cognitive deterioration, but Vivanti, Associate Professor of Early Detection and Intervention at the AJ Drexel Autism Institute in Philadelphia, Pennsylvania, knew that the scientific literature offered few clear answers.

“I was quite shocked to learn that we have such limited knowledge of the results as children with autism grow up and as they get older,” says Vivanti.

This prompted him to spend four years sifting through data from Medicaid, the largest health program in the United States, to determine the incidence of neurodegenerative diseases in 30- to 64-year-olds with autism. This group, he and his colleagues reported last month, are about 2.5 times more likely to be diagnosed with Alzheimer’s or other forms of dementia in the early stages than the general population.

The study is one of the few that found above-average rates of neurodegenerative diseases in autistic adults. Risk estimates for Parkinson’s disease in autistic people range from 15 to 20 percent, compared to about 1 percent in the general population. Similarly, the prevalence of dementia is less than 1 percent in non-autistic people, but around 4 percent in those with autism. Neither of these studies offers solid evidence, but their results are strong enough to warrant further investigation, researchers say.

“There’s enough data to look at, but we don’t quite know yet,” said Ruth Carper, an associate professor of psychology at San Diego State University in California, who studies autism from early development through adulthood.

Demonstrating a link between autism and neurodegeneration could take decades, but in the meantime, the work could provide another benefit: understanding what autism looks like in the elderly and how best to support them.

“We are recognizing more and more people with autism in their 60s and 70s,” says Sergio Starkstein, neurologist and professor of psychiatry at the University of Western Australia in Perth, “and knowing how they age is critical.”

Challenging diagnoses:

Studies in older autistic adults are not easy to conduct. For one, autism is a relatively new diagnosis: Gruyna Sukhareva first characterized the condition in 1925; Leo Kanner described it in 1943. But the diagnostic criteria of the disease have changed several times since then.

People diagnosed 50 years ago are likely to be different from those diagnosed 5 years ago, says Carper – a “cohort effect” that can make it difficult to extrapolate results across generations. Given that timeline, many older adults were never diagnosed with autism either, she says. “There may be a lot of people who are 70 years old and have autism but never got the label, so we can’t find them.”

Even if researchers can recruit older autistic adults, they are often difficult to diagnose as having neurodegenerative disease. Many autistic people already have Parkinson’s-like motor problems, such as a rigid gait or difficulty coordinating movements. And there is overlap between autism traits and dementia in terms of cognitive deficits, especially in executive skills like planning and problem solving, Vivanti says.

To date, there are no clinical guidelines for detecting dementia in autistic adults using cognitive tests designed for non-autistic adults, especially those who are minimally verbal, he says.

Attempts to use brain imaging to identify tangles, plaques, and other signs of neurodegeneration in people with autism are also not straightforward. The brains of autistic people can be structurally different from those of non-autistic people from an early age, making interpreting a brain scan a challenge, says Starkstein.

Starkstein became interested in the possible overlap between autism and neurodegenerative diseases after observing that many of the people he saw at his autism clinic had symptoms related to Parkinson’s disease. He conducted a follow-up study in 2015 and found that these traits affected 12 out of 37 of his autistic patients over 39.

Joseph Piven, a professor of psychiatry at the University of North Carolina at Chapel Hill, recruited another 19 autistic men in his own clinic for the same study and found three to have tremors and other motor symptoms related to Parkinson’s.

Some of these motor problems are common side effects of antipsychotics that many adults with autism take, Starkstein notes, but even out of 20 people in the cohort who weren’t taking these drugs at the time of the study, 4 had Parkinson’s disease. “This proportion is far higher than one would expect from a non-autistic population,” says Starkstein.

Similar high proportions of Parkinson’s-like characteristics have appeared in the self-reports of 296 older autistic adults in the Netherlands and 209 in the United States. Nearly 20 percent of people in the Dutch cohort and more than 30 percent in the US cohort described stiffness, tremors, slow movements, and problems buttoning and tightening, among other motor challenges.

It is premature to conclude from these results that autistic adults are more prone to Parkinson’s disease than non-autistic people, says lead researcher Hilde Geurts, professor of clinical neuropsychology at the University of Amsterdam. But she and her colleagues want to confirm or refute the findings by testing the motor skills of all study participants with an in-depth neurological exam, she says.

Converging results:

Some researchers have turned to large health registries to gather evidence. In 2015, a study of thousands of medical records by the health organization Kaiser Permanente found that Parkinson’s disease was around 30 times more common in adults with autism than in the general population. The study also found that autistic adults were about four times more likely to develop dementia than control subjects.

The dementia results are in line with Vivanti’s registry-based results: his team found that the prevalence of dementia is around 4 percent only in adults with autism and more than 5 percent in people with autism and intellectual disabilities – much higher than the prevalence of dementia in people without autism or intellectual disabilities, which is less than 1 percent.

Piven warns against relying solely on health records without personally assessing people. In his own work, he found older people diagnosed with autism in their medical records who were found to have frontotemporal dementia, a condition that causes severe social difficulties that clinicians confused with the social difficulties associated with autism . But the convergence of results from multiple studies of different types comes as no great surprise, he says.

Other neurodegenerative diseases have been linked to neurodegenerative disorders, Piven notes: For example, people with 22q11.2 deletion syndrome, a genetic disorder associated with autism, are at increased risk of early-onset Parkinson’s disease, and people with Down Syndrome have high rates of dementia and Alzheimer’s.

Why autistic people are at higher risk of developing neurodegenerative diseases is unknown, although some researchers speculate that, as with other neurodegenerative diseases, there is a genetic overlap. Chemical messengers, including serotonin and dopamine, are involved in both autism and Parkinson’s, and several genes involved in brain growth have emerged in both autism and dementia. In addition, compared to non-autistic people, autistic people have higher levels of beta-amyloid, the protein that forms plaques in the brains of people with Alzheimer’s disease, according to analysis of blood samples and post-mortem brains.

Any increased risk of dementia on the spectrum can also be related to lifestyle, says Vivanti. Participation in intellectual, educational and social offers can protect against cognitive decline and dementia, as research shows. “It is possible – but it is only speculation – that people with autism often encounter barriers to accessing these opportunities,” he says. To support this idea, autistic teenagers show a loss of adaptability when they leave school, according to a 2020 study.

“Autistic people fall behind in practical skills when they leave a structured environment – it’s not the same thing as degeneration, but it’s a well-documented fact,” said Catherine Lord, eminent professor of psychiatry at the University of California, Los Angeles . and a lead investigator on the study.

For about 30 years, Lord has tracked dozens of people with autism and taken basic behavioral and neurobiological measurements, starting in their mid-thirties. In the future, clinicians will need to follow such cohorts even longer and develop better tools to reliably diagnose motor or cognitive deterioration across the spectrum – even in people with minimal verbal or severe intellectual disabilities.

This is the only way researchers will ever be able to establish a definitive link between autism and neurodegeneration, says Lord – “It’s just crazy to have to wait 50 years.”

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