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Neurology. 2017 Apr 11;88(15):1431-1438. doi: 10.1212/WNL.0000000000003812. Epub 2017 Mar 10.

Cued memory decline in biomarker-defined preclinical Alzheimer disease.

Author information

1
From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown. kpapp@partners.org.
2
From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.

Abstract

OBJECTIVE:

To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging.

METHODS:

Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ+/- status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education.

RESULTS:

A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ+ participants were 3.55 times (95% confidence interval = 1.77-7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ- peers. Furthermore, Aβ+ participants who scored ≤46/48 had smaller hippocampal volumes (t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ2 = 14.30, p < 0.001), compared with their Aβ+ peers with intact total recall.

CONCLUSIONS:

Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ+ clinically normal individuals at greatest risk of short-term clinical progression.

PMID:
28283594
PMCID:
PMC5386436
DOI:
10.1212/WNL.0000000000003812
[Indexed for MEDLINE]
Free PMC Article

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