Research Paper Advance Articles

Age-related trends in amyloid positivity in Parkinson’s disease without dementia

Keiko Hatano1, , Masashi Kameyama2,3, , Masanori Kurihara1, , Kensuke Ohse3, , Ryoji Goto4, , Ryoko Ihara1, , Mana Higashihara1, , Renpei Sengoku5, , Yasushi Nishina1, , Kazutomi Kanemaru1, , Yuko Saito6, , Shigeo Murayama1,6,7, , Atsushi Iwata1, ,

  • 1 Department of Neurology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
  • 2 AI and Theoretical Image Processing, Research Team for Neuroimaging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
  • 3 Integrated Research Initiative for Living Well with Dementia, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
  • 4 Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan
  • 5 Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan
  • 6 Department of Neuropathology (The Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
  • 7 Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University, Osaka, Japan

Received: October 2, 2024       Accepted: July 24, 2025       Published: August 6, 2025      

https://doi.org/10.18632/aging.206297
How to Cite

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.

Abstract

Amyloid-beta (Aβ) plays a pivotal role in cognitive decline in Parkinson’s disease (PD). The prevalence of amyloid positivity, evaluated using the cerebrospinal fluid (CSF) of patients with PD without dementia in their sixties, is lower than that in individuals with normal cognition without PD diagnosis in the same age range. However, it is unclear whether this is also the case in patients with PD without dementia in their eighties. Eighty-nine patients with PD without dementia were retrospectively classified into two groups with a cut-off age of 73 years at diagnosis: a HIGH group and a LOW group, with mean age at diagnosis of 80.2 and 64.9 years, respectively. The prevalence of amyloid positivity was significantly higher in the HIGH (30.6%) than in the LOW group (10.0%) (p = 0.02). The prevalence of amyloid positivity in both groups was lower than that in participants with normal cognition in the same age range. Our findings may be attributed to the shorter preclinical stage of asymptomatic cerebral Aβ deposition in PD, resulting from Aβ accelerating the transition from the asymptomatic to dementia stage. We believe that our findings will incentivize further studies to identify the best disease-modifying therapy for early PD without dementia.

Abbreviations

Aβ42: amyloid-beta 42; AD: Alzheimer’s disease; AD continuum: Alzheimer’s continuum; ApoE: Apolipoprotein E; CSF: cerebrospinal fluid; DAT: dopamine transporter; DLB: dementia with Lewy bodies; H/M ratio: heart-to-mediastinum ratio; LB: Lewy body; MCI: mild cognitive impairment; MIBG: meta-iodobenzyl-guanidine; MMSE: Mini-Mental State Examination; MRI: magnetic resonance imaging; OH: orthostatic hypotension; PART: primary age-related tauopathy; PD: Parkinson’s disease; PDD: Parkinson’s disease with dementia; PET: positron emission tomography; p-tau: tau phosphorylated at threonine 181; RBD: rapid eye movement sleep behavior disorder; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; t-tau: total-tau.