TY - JOUR
T1 - A third of community-dwelling elderly with intermediate and high level of Alzheimer's neuropathologic changes are not demented
T2 - A meta-analysis
AU - Azarpazhooh, Mahmoud Reza
AU - Avan, Abolfazl
AU - Cipriano, Lauren E.
AU - Munoz, David G.
AU - Erfanian, Mahdiyeh
AU - Amiri, Amin
AU - Stranges, Saverio
AU - Hachinski, Vladimir
N1 - Funding Information:
We are grateful to Dr. Erin Abner (University of Kentucky College of Public Health) for providing us with the data of the SMART project and being helpful with our questions.
Funding Information:
The following are Supplementary data to this article: 85+S the Vantaa 85+ Study (Finland), 2017 (Tanskanen et al., 2017) 90+S the 90+ study (Orange County, California, US), 2012 (Corrada et al., 2012) and 2015 (Kawas et al., 2015) ACT the Adult Changes in Thought study, 2013 (Cholerton et al., 2013) AD Alzheimer’s disease AZSAND the Arizona Study of Aging and Neurodegenerative Disorders (Arizona, US), 2014 (Dugger et al., 2014) BRAiNS the Biologically Resilient Adults in Neurological Studies (Kentucky, US), 2015 (Abner et al., 2015; Schmitt et al., 2012) BB Braak and Braak CASI the Cognitive Abilities Screening Instrument CC75CS The Cambridge City over-75 s Cohort Study (Cambridge, UK), 2009 (Brayne et al., 2009) CERAD the Consortium to Establish a Registry for Alzheimer's Disease CI confidence interval EAS the Einstein Aging Study (Bronx, US), 2015 (Abner et al., 2015; Katz et al., 2012) HAAS the Honolulu Asia Aging Study (Honolulu), 2015 (Abner et al., 2015) and 2016 (White et al., 2016) KEAP the Klamath Exceptional Aging Project (US), 2015 (Abner et al., 2015; Kaye et al., 2009) MAP the Memory and Aging Project (Chicago, US), 2009 (Schneider et al., 2009), 2012 (Bennett et al., 2012b) and 2015 (Abner et al., 2015) MAPWU the Memory and Aging Project Washington University (Washington, US), 2005 (Abner et al., 2015; Galvin et al., 2005) MMSE Mini-Mental State Exam; MRC-CFAS, the Medical Research Council Cognitive Function and Ageing Study (UK), 2009 (Matthews et al., 2009) NIA-RIA the National Institute on Aging and the Ronald and Nancy Reagan Institute of the Alzheimer’s Association NS the Nun Study, 2015 (Abner et al., 2015) and 2016 (White et al., 2016) OBAS the Oregon Brain Aging Study (Oregon, US), 2000 and 2015 (Abner et al., 2015; Green et al., 2000) ROS the Religious Order Study (Chicago, US), 2009 (Schneider et al., 2009), 2012 (Bennett et al., 2012a), and 2015 (Abner et al., 2015) SMART the Statistical Modeling of Aging and Risk of Transition (SMART) Project, 2015 (Abner et al., 2015) VITAS the Vienna Transdanube Aging Study (Austria), 2013 (Kovacs et al., 2013)
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Autopsy
KW - Community health planning
KW - Dementia
KW - Neuropathology
UR - http://www.scopus.com/inward/record.url?scp=85077463190&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2019.101002
DO - 10.1016/j.arr.2019.101002
M3 - Review article
C2 - 31899366
AN - SCOPUS:85077463190
SN - 1568-1637
VL - 58
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 101002
ER -