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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.

TitleAssociation of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
Publication TypeJournal Article
Year of Publication2018
AuthorsJansen, W. J., Ossenkoppele R., Tijms B. M., Fagan A. M., Hansson O., Klunk W. E., et al.
Corporate AuthorsAmyloid Biomarker Study Group
JournalJAMA Psychiatry
Volume75
Issue1
Pagination84-95
Date Published2018 Jan 01
ISSN2168-6238
Abstract

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.

DOI10.1001/jamapsychiatry.2017.3391
Alternate JournalJAMA Psychiatry
PubMed ID29188296
PubMed Central IDPMC5786156
Grant ListP30 AG010124 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
C06 RR018898 / RR / NCRR NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P01 AG026276 / AG / NIA NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
RF1 AG025516 / AG / NIA NIH HHS / United States
R01 AG045611 / AG / NIA NIH HHS / United States
P01 AG025204 / AG / NIA NIH HHS / United States

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