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J Alzheimers Dis. 2015;45(1):253-68. doi: 10.3233/JAD-142451.

Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e.

Author information

1
Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore.

Abstract

BACKGROUND:

Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression.

OBJECTIVE:

To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD.

METHODS:

356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined.

RESULTS:

Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers.

CONCLUSIONS:

EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.

KEYWORDS:

APOE genotype; Alzheimer's disease; amyloid-β deposition; magnetic resonance imaging; mild cognitive impairment; preclinical

PMID:
25524955
DOI:
10.3233/JAD-142451
[Indexed for MEDLINE]

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