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Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements.

ABSTRACT: Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid ? (A?) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the A? cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.

SUBMITTER: Tadokoro K

PROVIDER: S-EPMC7139972 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements.

Tadokoro Koh K Ohta Yasuyuki Y Inufusa Haruhiko H Loon Alan Foo Nyuk AFN Abe Koji K

International journal of molecular sciences 20200313 6

Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative s ...[more]

PMID: 32183152

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Project description:BACKGROUND:There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5?years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11?years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. METHODS:This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n =?868) compared to those who remained cognitively unimpaired during the same time period (n =?989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer's Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11?years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score. RESULTS:The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities +?2.24*MMSE Orientation to Time?+?2.14*MMSE Orientation to Place +?0.53*Logical Memory Delayed Recall +?1.36* Word List-Delayed Recall +?0.68*Judgment of Line Orientation +?1.39*Raven's Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was -?1.10 over 1 year. CONCLUSIONS:The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11?years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.

Dataset Information

Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements.

Publications

Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements.

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