Causes and Patterns of Dementia: An Update in the Era of Redefining Alzheimer's Disease

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Abstract

The burden of dementia continues to increase as the population ages, with no disease-modifying treatments available. However, dementia risk appears to be decreasing, and progress has been made in understanding its multifactorial etiology. The 2018 National Institute on Aging–Alzheimer's Association (NIA-AA) research framework for Alzheimer's disease (AD) defines AD as a biological process measured by brain pathology or biomarkers, spanning the cognitive spectrum from normality to dementia. This framework facilitates interventions in the asymptomatic space and accommodates knowledge that many additional pathologies (e.g., cerebrovascular) contribute to the Alzheimer's dementia syndrome. The framework has implications for how we think about risk factors for “AD”: Many commonly accepted risk factors are not related to AD pathology and would no longer be considered risk factors for AD. They may instead be related to other pathologies or resilience to pathology. This review updates what is known about causes, risk factors, and changing patterns of dementia, addressing whether they are related to AD pathology/biomarkers, other pathologies, or resilience.

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Most cited references 99

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Howard Aizenstein, Robert Nebes, Judith Saxton … (2008)

To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). University medical center. From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. Regional PiB retention and cognitive test performance. Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

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Author and article information

Journal

Title: Annual Review of Public Health

Abbreviated Title: Annu. Rev. Public Health

Publisher: Annual Reviews

ISSN (Print): 0163-7525

ISSN (Electronic): 1545-2093

Publication date Created: April 2019

Publication date (Print): April 2019

Volume: 40

Issue: 1

Pages: 65-84

Affiliations

[1 ]Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA;

[2 ]Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois 60612, USA

[3 ]Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA

Article

DOI: 10.1146/annurev-publhealth-040218-043758

PubMed ID: 30642228

SO-VID: f1d224c3-4865-47ef-8918-1d39a5b6a194

History

ScienceOpen disciplines: Neurology,Health & Social care,Clinical Psychology & Psychiatry,Public health

Data availability:

ScienceOpen disciplines: Neurology, Health & Social care, Clinical Psychology & Psychiatry, Public health

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