Study ties age at Parkinson’s diagnosis to brain amyloid buildup
Those diagnosed later in life had more buildup regardless of cognitive status
People diagnosed with Parkinson’s disease in their 80s were significantly more likely to show evidence of brain buildup of amyloid-beta, a protein linked to cognitive decline in Alzheimer’s disease, than those diagnosed at a younger age, a study found.
Neither group showed signs of cognitive impairment. The researchers said assessing amyloid-beta accumulation in Parkinson’s — even in those without cognitive problems — could help identify patients at greater risk of future dementia and those who may benefit most from early, targeted interventions.
“We believe that our findings will incentivize further studies to identify the best disease-modifying therapy for early [Parkinson’s] without dementia,” researchers wrote.
The study, “Age-related trends in amyloid positivity in Parkinson’s disease without dementia,” was published in Aging.
In Parkinson’s, nerve cells gradually die, largely due to the accumulation of Lewy bodies — toxic protein clumps primarily composed of alpha-synuclein protein. This cell loss gives rise to the disease’s hallmark motor symptoms, including tremors, stiffness, and slowed movement. Patients may also experience cognitive problems, which can progress to dementia.
Protein buildup and cognitive decline
Amyloid-beta and tau, proteins associated with Alzheimer’s disease, are also believed to play a role in Parkinson’s cognitive changes. Amyloid-beta, in particular, forms sticky plaques that build up in the brain and are linked to cognitive decline in Parkinson’s and Alzheimer’s.
But the role of these proteins in patients with Parkinson’s who do not show cognitive problems remains poorly understood.
Studies have found that people in their 60s with Parkinson’s but no dementia are less likely to have amyloid build-up than healthy people of the same age. The researchers set out to determine whether this also holds true for patients diagnosed with Parkinson’s in their 80s.
The team of researchers in Japan reviewed records from 89 people diagnosed with Parkinson’s and showing no signs of dementia at the Tokyo Metropolitan Institute for Geriatrics and Gerontology between April 2013 and December 2022. All had been diagnosed within five years of their first motor symptoms, and patients who were diagnosed at age 40 or younger were excluded.
Patients were divided into two groups: 40 who were diagnosed before the age of 73 (average age 64.9), and 49 who were diagnosed at 73 or older (average age of 80.2). Men and women were represented in roughly equal numbers in both groups, and the overall severity of Parkinson’s symptoms was also similar.
The older group, on average, had fewer years of education and scored slightly lower on memory and thinking tests. Still, nearly all patients in both groups were considered cognitively normal, with 91.8% in the older group and 95% in the younger group showing no signs of dementia.
In cerebrospinal fluid samples, soluble levels of amyloid-beta — which drop as amyloid plaques build in the brain — tended to be lower in older patients, although the difference wasn’t statistically significant. Tau proteins, which rise as nerve cell damage increases, showed a clear and significant increase with age. These results suggest more ongoing neuronal injury in older Parkinson’s patients, even in the absence of overt cognitive impairment.
However, evidence of amyloid build-up was found in 30.6% of people diagnosed at 73 or older —  three times the rate seen in those diagnosed before age 73 (10%).
The findings point to an age-related increase in amyloid buildup in people with Parkinson’s who don’t yet have dementia. These rates were still lower than in healthy people of similar age in the general population, which the researchers said may reflect differences in the way amyloid builds up in Parkinson’s.
They hypothesized that Parkinson’s may shorten the phase when plaques form in the brain without causing symptoms. As a result, once amyloid appears, patients with Parkinson’s could move more quickly from normal cognition to dementia, leaving less time to detect amyloid in older patients who remain cognitively normal.
They also observed that tau protein levels rose with age. Since tau increases as nerve cells are damaged, this points to more ongoing brain injury in older people with Parkinson’s, which could further raise the risk of dementia.
“To clarify the causal relationship between [amyloid-beta] positivity and [Parkinson’s] progression, a longitudinal, large-scale, multicenter study is needed,” the researchers wrote. “It is essential to verify whether [amyloid-beta] deposition accelerates dementia onset in [Parkinson’s] patients in their eighties, as suggested in our study, similarly to those in their sixties.”
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