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

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.

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  • Authors+Show Affiliations

    ,

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

    ,

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

    ,

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

    Source

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Analysis of Variance
    Apolipoproteins E
    Atrophy
    Biomarkers
    Brain
    Cognition Disorders
    Cohort Studies
    Dementia
    Female
    Humans
    Image Processing, Computer-Assisted
    Magnetic Resonance Imaging
    Male
    Neuropsychological Tests
    Peptide Fragments
    Psychiatric Status Rating Scales

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    25524955

    Citation

    Susanto, Thomas Adi Kurnia, et al. "Cognition, Brain Atrophy, and Cerebrospinal Fluid Biomarkers Changes From Preclinical to Dementia Stage of Alzheimer's Disease and the Influence of Apolipoprotein E." Journal of Alzheimer's Disease : JAD, vol. 45, no. 1, 2015, pp. 253-68.
    Susanto TA, Pua EP, Zhou J, et al. Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e. J Alzheimers Dis. 2015;45(1):253-68.
    Susanto, T. A., Pua, E. P., & Zhou, J. (2015). Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e. Journal of Alzheimer's Disease : JAD, 45(1), pp. 253-68. doi:10.3233/JAD-142451.
    Susanto TA, et al. Cognition, Brain Atrophy, and Cerebrospinal Fluid Biomarkers Changes From Preclinical to Dementia Stage of Alzheimer's Disease and the Influence of Apolipoprotein E. J Alzheimers Dis. 2015;45(1):253-68. PubMed PMID: 25524955.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e. AU - Susanto,Thomas Adi Kurnia, AU - Pua,Emmanuel Peng Kiat, AU - Zhou,Juan, AU - ,, PY - 2014/12/20/entrez PY - 2014/12/20/pubmed PY - 2016/3/2/medline KW - APOE genotype KW - Alzheimer's disease KW - amyloid-β deposition KW - magnetic resonance imaging KW - mild cognitive impairment KW - preclinical SP - 253 EP - 68 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 45 IS - 1 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/25524955/Cognition_brain_atrophy_and_cerebrospinal_fluid_biomarkers_changes_from_preclinical_to_dementia_stage_of_Alzheimer's_disease_and_the_influence_of_apolipoprotein_e_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-142451 DB - PRIME DP - Unbound Medicine ER -