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CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.

ABSTRACT: Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/A?42 in predicting rates of cognitive decline in early AD.Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and A?42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time.Baseline CSF VILIP-1 and VILIP-1/A?42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 ?560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/A?42, and p-tau181/A?42 also predicted more rapid cognitive decline in CDR-SB and global scores over time.These findings suggest that CSF VILIP-1 and VILIP-1/A?42 predict rates of global cognitive decline similarly to tau and tau/A?42, and may be useful CSF surrogates for neurodegeneration in early AD.

SUBMITTER: Tarawneh R

PROVIDER: S-EPMC3306162 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.

Tarawneh R R Lee J-M JM Ladenson J H JH Morris J C JC Holtzman D M DM

Neurology 20120222 10

<h4>Objective</h4>Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early A ...[more]

PMID: 22357717

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Project description:ImportanceIndicators of early-life cognitive enrichment (ELCE) have been associated with slower cognitive decline and decreased dementia in late life. However, the mechanisms underlying this association have not been elucidated.ObjectiveTo examine the association of ELCE with late-life Alzheimer disease (AD) and other common dementia-related pathological changes.Design, setting, and participantsThis clinical-pathological community-based cohort study, the Rush Memory and Aging Project, followed up participants before death for a mean (SD) of 7.0 (3.8) years with annual cognitive and clinical assessments. From January 1, 1997, through June 30, 2019, 2044 participants enrolled, of whom 1018 died. Postmortem data were leveraged from 813 participants. Data were analyzed from April 12, 2019, to February 20, 2020.ExposuresFour indicators of ELCE (early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction) were obtained by self-report at the study baseline, from which a composite measure of ELCE was derived.Main outcomes and measuresA continuous global AD pathology score derived from counts of diffuse plaques, neuritic plaques, and neurofibrillary tangles.ResultsThe 813 participants included in the analysis had a mean (SD) age of 90.1 (6.3) years at the time of death, and 562 (69%) were women. In a linear regression model controlled for age at death, sex, and educational level, a higher level of ELCE was associated with a lower global AD pathology score (estimate, -0.057; standard error, 0.022; P = .01). However, ELCE was not associated with any other dementia-related pathological changes. In addition, a higher level of ELCE was associated with less cognitive decline (mean [SD], -0.13 [0.19] units per year; range, -1.74 to 0.85). An indirect effect through AD pathological changes constituted 20% of the association between ELCE and the rate of late-life cognitive decline, and 80% was a direct association.Conclusions and relevanceThese findings suggest that ELCE was associated with better late-life cognitive health, in part through an association with fewer AD pathological changes.

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CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.

Publications

CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.

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