Abstract
Objective To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden.
Method The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of β-amyloid (Aβ)42, Aβ40, total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging–Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score >0 were excluded, leaving 259 cognitively unimpaired individuals.
Results The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T−/N− was 13.1%, A+/T−/N+ was 7.3%, A+/T+/N+ was 2.3%, A−/T−/N+ was 18.9%, and A−/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE ε4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T−/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2.
Conclusion The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- AR-AD=
- at risk for Alzheimer disease;
- CDR=
- Clinical Dementia Rating;
- CFAS=
- Cognitive Function and Ageing;
- DSM-III-R=
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
- DSM-V=
- Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
- IWG-2=
- International Working Group-2;
- LP=
- lumbar puncture;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- NIA-AA=
- National Institute on Aging–Alzheimer’s Association;
- p-tau=
- phosphorylated tau;
- SNAP=
- non–Alzheimer disease pathophysiology;
- SNP=
- single nucleotide polymorphism;
- t-tau=
- total tau
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by Swedish Research Council.
- Received September 28, 2017.
- Accepted in final form February 20, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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