Dataset Information

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.

ABSTRACT:

Objective

Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and A? accumulation in adults with amnestic mild cognitive impairment (aMCI) and high A?.

Methods

Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.

Results

In individuals with aMCI and high A?, Met carriers showed significant and large decline in episodic memory (d?=?0.90, p?=?.020) and hippocampal volume (d?=?0.98, p?=?.035). BDNF Val66Met was unrelated to the rate of A? accumulation (d?=?-0.35, p?=?.401).

Conclusions

Although preliminary due to the small sample size, results of this study suggest that high A? levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.

SUBMITTER: Lim YY

PROVIDER: S-EPMC3903533 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.

Lim Yen Ying YY Villemagne Victor L VL Laws Simon M SM Ames David D Pietrzak Robert H RH Ellis Kathryn A KA Harrington Karra K Bourgeat Pierrick P Bush Ashley I AI Martins Ralph N RN Masters Colin L CL Rowe Christopher C CC Maruff Paul P

PloS one 20140127 1

<h4>Objective</h4>Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairme ...[more]

PMID: 24475133

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Project description:Alzheimer's disease is a heterogeneous disorder. Understanding the biological basis for this heterogeneity is key for developing personalized medicine. We identified atrophy subtypes in Alzheimer's disease dementia and tested whether these subtypes are already present in prodromal Alzheimer's disease and could explain interindividual differences in cognitive decline. First we retrospectively identified atrophy subtypes from structural MRI with a data-driven cluster analysis in three datasets of patients with Alzheimer's disease dementia: discovery data (dataset 1: n = 299, age = 67 ± 8, 50% female), and two independent external validation datasets (dataset 2: n = 181, age = 66 ± 7, 52% female; dataset 3: n = 227, age = 74 ± 8, 44% female). Subtypes were compared on clinical, cognitive and biological characteristics. Next, we classified prodromal Alzheimer's disease participants (n = 603, age = 72 ± 8, 43% female) according to the best matching subtype to their atrophy pattern, and we tested whether subtypes showed cognitive decline in specific domains. In all Alzheimer's disease dementia datasets we consistently identified four atrophy subtypes: (i) medial-temporal predominant atrophy with worst memory and language function, older age, lowest CSF tau levels and highest amount of vascular lesions; (ii) parieto-occipital atrophy with poor executive/attention and visuospatial functioning and high CSF tau; (iii) mild atrophy with best cognitive performance, young age, but highest CSF tau levels; and (iv) diffuse cortical atrophy with intermediate clinical, cognitive and biological features. Prodromal Alzheimer's disease participants classified into one of these subtypes showed similar subtype characteristics at baseline as Alzheimer's disease dementia subtypes. Compared across subtypes in prodromal Alzheimer's disease, the medial-temporal subtype showed fastest decline in memory and language over time; the parieto-occipital subtype declined fastest on executive/attention domain; the diffuse subtype in visuospatial functioning; and the mild subtype showed intermediate decline in all domains. Robust atrophy subtypes exist in Alzheimer's disease with distinct clinical and biological disease expression. Here we observe that these subtypes can already be detected in prodromal Alzheimer's disease, and that these may inform on expected trajectories of cognitive decline.

Dataset Information

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.

Objective

Methods

Results

Conclusions

Publications

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.

Similar Datasets

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