A third of community-dwelling elderly with intermediate and high level of Alzheimer's neuropathologic changes are not demented: A meta-analysis

Mahmoud Reza Azarpazhooh; Abolfazl Avan; Lauren E Cipriano; David G Munoz; Mahdiyeh Erfanian; Amin Amiri; Saverio Stranges; Vladimir Hachinski

doi:10.1016/j.arr.2019.101002

A third of community-dwelling elderly with intermediate and high level of Alzheimer's neuropathologic changes are not demented: A meta-analysis

Ageing Res Rev. 2020 Mar:58:101002. doi: 10.1016/j.arr.2019.101002. Epub 2019 Dec 30.

Authors

Mahmoud Reza Azarpazhooh¹, Abolfazl Avan², Lauren E Cipriano³, David G Munoz⁴, Mahdiyeh Erfanian⁵, Amin Amiri⁶, Saverio Stranges⁷, Vladimir Hachinski⁸

Affiliations

¹ Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: reza.azarpazhooh@lhsc.on.ca.
² Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abolfazl.avan@gmail.com.
³ Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Ivey Business School, Western University, London, ON, Canada. Electronic address: lcipriano@ivey.uwo.ca.
⁴ Department of Pathology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Research, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. Electronic address: munozd@smh.ca.
⁵ Department of Statistics, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: m.erfaniyan@mail.um.ac.ir.
⁶ Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amin.amiri.a@gmail.com.
⁷ Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Department of Family Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg. Electronic address: saverio.stranges@uwo.ca.
⁸ Department of Clinical Neurological Sciences, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Vladimir.Hachinski@lhsc.on.ca.

PMID: 31899366
DOI: 10.1016/j.arr.2019.101002

Abstract

This systematic review and meta-analysis assessed the bidirectional association between AD pathology and dementia in community-dwelling elderly populations. We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and references of the pertinent articles for community/population-based longitudinal cohorts with regular assessment of cognitive status of participants followed by postmortem neuropathology data, with no language and date restrictions, until 20 September 2019. Finally, we retrieved 18 articles with data from 17 cohorts comprising 4677 persons. Dementia was twice as likely in participants with definitive neuropathological indicator for AD compared to those without it: moderate/high Braak and Braak (BB) stages III-VI of neurofibrillary tangles (54 % vs. 26 % in participants with BB stages 0-II), the Consortium to Establish a Registry for AD (CERAD) moderate/frequent neuritic plaques scores (64 % vs. 33 % in participants with CERAD none/infrequent), and National Institute on Aging and the Reagan Institute of the Alzheimer's Association criteria intermediate/high AD probability (52 % vs. 28 % in participants with no/low AD probability). Accordingly, a substantial proportion of community-dwelling elderly people with definitive AD pathology may not develop dementia. Brain reserve or contribution of other factors and pathologies, such as vascular and degenerative pathology to dementia might explain this apparent discrepancy. These findings also suggest caution in equating Alzheimer pathology biomarkers with dementia.

Keywords: Alzheimer disease; Autopsy; Community health planning; Dementia; Neuropathology.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Aged
Alzheimer Disease* / complications
Alzheimer Disease* / epidemiology
Brain
Dementia* / epidemiology
Dementia* / etiology
Humans
Independent Living
Neurofibrillary Tangles
Neuropathology
Plaque, Amyloid