image: Figure 1. Relationship between Aβ42, p-tau, or t-tau levels and age at diagnosis. Scatter plots demonstrate the relationship between age at diagnosis and CSF biomarkers. Least squares regression lines are included where Pearson’s correlation analysis was performed. A negative correlative tendency (r = -0.19, p = 0.08) was observed between CSF Aβ42 levels (pg/mL) and age at diagnosis. (A) A positive correlative tendency (r = 0.20, p = 0.06) was observed between CSF p-tau levels (pg/mL) and age at diagnosis. (B) Significant positive correlation was observed between CSF t-tau levels (pg/mL) and age at diagnosis (r = 0.35, p < 0.001). (C) The association between age at diagnosis and each AT(N) category for CSF Aβ42, p-tau, and t-tau are shown. (D–F), with Pearson’s correlation coefficient not calculated for the non-AD category due to the small number of cases. CSF Aβ42 and age at diagnosis showed negative correlative tendency (r =-0.36, p= 0.13) in the AD continuum category, whereas this tendency was not evident in the normal category (r = 0.08, p = 0.54). (D) CSF p-tau and age at diagnosis showed a significant positive correlation in the AD continuum category (r = 0.48, p = 0.04), but showed no obvious tendency in the normal category. (E) CSF t-tau and age at diagnosis showed a significant positive correlation in both patients in AD continuum category (r = 0.53, p = 0.02) and normal category (r = 0.48, p < 0.001). (F) Data in AD continuum category are plotted in red, normal category in black, and non-AD pathologic change category in light blue (D–F). Aβ42 = amyloid-beta 42, p-tau = phosphorylated tau, t-tau = total tau, * = p < 0.05, *** = p < 0.001. r and p represent Pearson’s correlation and significance, respectively.
Credit: Copyright: © 2025 Hatano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“We believe that our findings will incentivize further studies to identify the best disease-modifying therapy for early PD without dementia.”
BUFFALO, NY — September 16, 2025 — A new research paper was published in Volume 17, Issue 8 of Aging-US on August 6, 2025, titled “Age-related trends in amyloid positivity in Parkinson’s disease without dementia.”
In this study, led by first author Keiko Hatano and corresponding author Masashi Kameyama from the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan, researchers found that patients with Parkinson’s disease (PD) diagnosed in their 80s showed a significantly higher rate of amyloid positivity—an indicator associated with Alzheimer’s disease—compared to those diagnosed at a younger age. Importantly, none of the participants had dementia. These findings suggest that older patients with PD may face a greater risk of future cognitive decline and could benefit from early screening for Alzheimer’s-related brain changes.
Amyloid-beta is considered a key marker of cognitive decline. While it is known that amyloid accumulation contributes to PD with dementia, its role in patients who have not developed cognitive problems remains less understood. This study aimed to explore how age influences amyloid buildup in people with PD who do not yet show signs of dementia.
The researchers analyzed data from 89 individuals with PD and no signs of dementia. Participants were divided into two age-based groups: those diagnosed before age 73 (LOW group) and those diagnosed at age 73 or older (HIGH group). Using cerebrospinal fluid samples, they measured levels of amyloid-beta, a standard method for detecting early Alzheimer’s-related changes. The findings revealed that 30.6% of the older group tested positive for amyloid, compared to just 10.0% in the younger group.
“[…] we elucidated the prevalence of amyloid positivity in patients with PD without dementia, whose mean age at diagnosis was 80.2 years, using CSF Aβ42 levels.”
Interestingly, both age groups of Parkinson’s patients had a lower rate of amyloid positivity than cognitively normal individuals of the same age in the general population. This unexpected result suggests that PD may alter how amyloid accumulates in the brain, possibly shortening the phase in which amyloid builds up silently before symptoms appear. The authors suggest that amyloid buildup could accelerate the transition from healthy cognition to dementia in patients with PD. The study also observed age-related associations with other biological markers of Alzheimer’s disease, such as tau protein levels.
As the global population continues to age and the number of older adults diagnosed with PD grows, identifying early warning signs of cognitive decline becomes increasingly important. These findings may help inform future screening approaches and support the development of therapies aimed at delaying or preventing dementia in people with Parkinson’s disease.
DOI: https://doi.org/10.18632/aging.206297
Corresponding author: Masashi Kameyama – kame-tky@umin.ac.jp
Abstract video: https://www.youtube.com/watch?v=AP8S9evzCJw
Keywords: aging, amyloid positivity, Parkinson’s disease without dementia, cerebrospinal fluid Aβ42
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Journal
Aging-US
Method of Research
News article
Subject of Research
People
Article Title
Age-related trends in amyloid positivity in Parkinson’s disease without dementia
Article Publication Date
6-Aug-2025
COI Statement
The authors have no conflicts of interest to declare.