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. 2023 May;19(5):1705-1713.
doi: 10.1002/alz.12762. Epub 2022 Oct 4.

Mid- and later-life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility-Reykjavik Study

Blossom C M Stephan  1 , Denise M Gaughan  2 , Steven Edland  3   4 , Villi Gudnason  5   6 , Lenore J Launer  2 , Lon R White  7
Affiliations

Mid- and later-life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility-Reykjavik Study

Blossom C M Stephan et al. Alzheimers Dement. 2023 May.

Abstract

Introduction: Dementia prediction models are necessary to inform the development of dementia risk reduction strategies. Here, we examine the utility of neuropathological-based risk scores to predict clinical dementia.

Methods: Models were developed for predicting Alzheimer's disease (AD) and non-AD neuropathologies using the Honolulu Asia Aging neuropathological sub-study (HAAS; n = 852). Model accuracy for predicting clinical dementia, over 30 years, was tested in the non-autopsied HAAS sample (n = 2960) and the Age, Gene/Environment Susceptibility-Reykjavik Study (n = 4614).

Results: Different models were identified for predicting neurodegenerative and vascular neuropathology (c-statistic range: 0.62 to 0.72). These typically included age, APOE, and a blood pressure-related measure. The neurofibrillary tangle and micro-vascular lesion models showed good accuracy for predicting clinical vascular dementia.

Discussion: There may be shared risk factors across dementia-related lesions, suggesting common pathways. Strategies targeting these models may reduce risk or postpone clinical symptoms of dementia as well as reduce neuropathological burden associated with AD and vascular lesions.

Keywords: Alzheimer's disease; dementia; neuropathology; risk prediction; vascular disease.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Comparison of the discriminative accuracy (AUC and 95% CI) for neurodegenerative derived risk scores when predicting pathology or a clinical diagnosis of dementia (i.e., AD, VaD, or mixed dementia) in HAAS and AGES-Reykjavik. AD, clinical diagnosis of Alzheimer’s disease; AGES, Age, Gene/Environment Susceptibility-Reykjavik Study; DEM, clinical diagnosis of dementia (all cause); HAAS, Honolulu Asia Aging Study; NIA-Reagan, National Institutes of Ageing -Reagan derived score; VD, clinical diagnosis of vascular dementia.
See this image and copyright information in PMC

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