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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands; Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Department of Geriatrics, Karolinska University Hospital Huddinge, Section of Clinical Geriatrics, Institution of NVS, Karolinska Institutet, Stockholm, Sweden. (Amyloid Biomarker Study Group)ORCID iD: 0000-0001-6863-6679
Number of Authors: 1192018 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 75, no 1, p. 84-95Article in journal (Refereed) Published
Abstract [en]

Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.

Objective: To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.

Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.

Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.

Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.

Conclusions and Relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

Place, publisher, year, edition, pages
American Medical Association , 2018. Vol. 75, no 1, p. 84-95
National Category
Medical and Health Sciences Gerontology, specialising in Medical and Health Sciences
Identifiers
URN: urn:nbn:se:oru:diva-79268DOI: 10.1001/jamapsychiatry.2017.3391ISI: 000419177700014PubMedID: 29188296Scopus ID: 2-s2.0-85040468555OAI: oai:DiVA.org:oru-79268DiVA, id: diva2:1387122
Note

Funding Agencies:

United States Department of Health & Human Services National Institutes of Health (NIH) - USA, NIH National Center for Research Resources (NCRR), Appeared in article as NCRR NIH HHS, Grant number: C06 RR018898

United States Department of Health & Human Services National Institutes of Health (NIH) - USA, NIH National Institute on Aging (NIA), Appeared in article as NIA NIH HHS, Grant numbers: R01 AG045611, RF1 AG025516, P50 AG005133, P01 AG026276, P50 AG005681, P01 AG003991, P30 AG010124, P50 AG023501, P01 AG025204

Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved

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Freund-Levi, Yvonne

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