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Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

ABSTRACT: We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ?4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ?4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

SUBMITTER: Lorius N

PROVIDER: S-EPMC4366000 | biostudies-literature | 2015 Jan-Mar

REPOSITORIES: biostudies-literature

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Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

Lorius Natacha N Locascio Joseph J JJ Rentz Dorene M DM Johnson Keith A KA Sperling Reisa A RA Viswanathan Anand A Marshall Gad A GA

Alzheimer disease and associated disorders 20150101 1

We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-e ...[more]

PMID: 24787033

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Project description:IMPORTANCE:A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. OBJECTIVE:To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes. DESIGN, SETTING, AND PARTICIPANTS:Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's Disease Neuroimaging Initiative. This prospective longitudinal study across North America included individuals with normal cognition (n = 90), mild cognitive impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up ongoing. MAIN OUTCOMES AND MEASURES:Cerebrospinal fluid VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, and executive function) using a general linear model and longitudinally using mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid ?-amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers. RESULTS:Vascular endothelial growth factor was associated with baseline hippocampal volume (t277 = 2.62; P =?.009), longitudinal hippocampal atrophy (t858 = 2.48; P =?.01), and longitudinal decline in memory (t1629 = 4.09; P <?.001) and executive function (t1616 = 3.00; P =?.003). Vascular endothelial growth factor interacted with tau in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory decline (t1610 = 2.49; P =?.01), and executive function decline (t1597 = 3.71; P <?.001). Vascular endothelial growth factor interacted with ?-amyloid 42 in predicting longitudinal memory decline (t1618 = -2.53; P = .01). CONCLUSIONS AND RELEVANCE:Elevated cerebrospinal fluid VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared strongest in the presence of enhanced AD biomarkers, suggesting that VEGF may be particularly beneficial in individuals showing early hallmarks of the AD cascade. Future work should evaluate the interaction between VEGF expression in vitro and pathologic burden to address potential mechanisms.

Dataset Information

Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

Publications

Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

Similar Datasets

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