A neurodegenerative vascular burden index and the impact on cognition

Sebastian Heinzel; Inga Liepelt-Scarfone; Benjamin Roeben; Isabella Nasi-Kordhishti; Ulrike Suenkel; Isabel Wurster; Kathrin Brockmann; Andreas Fritsche; Raphael Niebler; Florian G Metzger; Gerhard W Eschweiler; Andreas J Fallgatter; Walter Maetzler; Daniela Berg

doi:10.3389/fnagi.2014.00161

A neurodegenerative vascular burden index and the impact on cognition

Front Aging Neurosci. 2014 Jul 9:6:161. doi: 10.3389/fnagi.2014.00161. eCollection 2014.

Authors

Affiliations

¹ Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen , Tübingen , Germany.
² Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen , Tübingen , Germany ; German Center for Neurodegenerative Diseases (DZNE) , Tübingen , Germany.
³ Department of Internal Medicine IV, University of Tübingen , Tübingen , Germany.
⁴ Department of Psychiatry and Psychotherapy, University of Tübingen , Tübingen , Germany ; Geriatric Center, University Hospital Tübingen , Tübingen , Germany.
⁵ Department of Psychiatry and Psychotherapy, University of Tübingen , Tübingen , Germany.

Abstract

A wide range of vascular burden factors has been identified to impact vascular function and structure as indicated by carotid intima-media thickness (IMT). On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI). Since many vascular factors increase the risk of Alzheimer's disease (AD), a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages. We investigated an elderly cohort at risk for neurodegeneration (TREND study, n = 1102) for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication, and/or blood marker data) were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and the consortium to establish a registry for Alzheimer's disease (CERAD) neuropsychological battery. IMT was significantly predicted by age (standardized β = 0.26), sex (0.09; males > females) and the factors included in the VBI: obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and atherosclerosis (0.05), whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT ( ≥ 1.0 mm). The VBI showed an impact on executive control [log(TMT B-A), p = 0.047] and a trend toward decreased global cognitive function (CERAD total score, p = 0.057) independent of age, sex, and education. A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of this risk cohort will reveal the value of the VBI as prodromal marker for cognitive decline and AD.

Keywords: Alzheimer’s disease; CERAD neuropsychological battery; Tübinger evaluation of risk factors for early detection of neurodegeneration (TREND) study; carotid intima-media thickness; neurodegeneration; prodromal marker; trail-making test; vascular burden.