Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia

Abstract

Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT, densitometry, perfusions, and cognitive testing among neurologically and cognitively normative aging volunteers. A total of 224 normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59.5 ± 15.8 years. Mean follow-up is 5.8 ± 3.3 years. At follow-up, 22 developed mild cognitive impairment (41 CCSE ≥ −3), 19 became demented—8 with Vascular type (VAD), 11 with Alzheimer’s type (DAT)—and 183 remain cognitively unchanged. Cerebral atrophy, tissue densities, and perfusions were measured by Xe-CT. After age 60, cerebral atrophy, ventricular enlargement, and polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis, and leuko-araiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, and male gender. At age 71.5 ± 11.9, mild cognitive impairment began accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with VAD. Excessive cortical perfusional decrease, gray and white matter hypodensities, and cerebral atrophy correlate with cognitive decline.

Introduction

As longevity increases worldwide, age-related dementias are burgeoning. Early identification and institution of preventive measures for risk factors predisposing to cognitive decline and treatment of mild cognitive impairment are of high priority. Epidemiologic, longitudinal studies of the elderly have already identified risk factors for cerebral degenerative changes and associated dementias [1], [14], [25], [34], [38], [39], [43], [46]. Risk factors predisposing to vascular dementias (VAD) and Alzheimer’s (DAT) are primarily cardiovascular and genetically determined [1], [14], [25], [46], [56]. Cross-sequential analyses of VAD indicate that control of stroke risk factors delay or prevent strokes and reverse cognitive impairment [31], [40]. Multiplicity of risk factors geometrically increase strokes and cognitive impairments.

As a result, a multifactorial pathogenesis of VAD has evolved [14], [32], [34]. Risks multiply in frequency and severity during aging and not only cause VAD but also complicate DAT, predisposing to higher prevalence of DAT among the elderly with heart disease [25] and among those with hypertension [55]. Similar risks probably contribute to subtle cognitive impairments and mild cognitive decline [43], [48]. Optimal identification of risks for subtle cognitive decline require longitudinal studies among normative populations at entry, followed with serial cognitive testing.

Studies of cerebral degenerative and functional changes during aging are sparse and have been confounded by different concepts and definitions of “normal” [32]. Rates of cerebral degenerative and functional changes differ widely from one person to another, which cannot be identified by group comparisons. We have previously described risk factors associated with cognitive decline and dementia in a small cohort of normal volunteers [1]. We have now added 32 additional subjects and followed this group for a longer interval of almost twice as long (5.8 years versus 3 years) and have identified and analyzed mild cognitive impairment and dementia that were not examined previously.