EpidemiologyRisk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia
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.
Section snippets
Methods
Two hundred twenty-four (n = 224:118 female, 106 male) cognitively and neurologically normative subjects (mean age 59.5 ± 15.8, 22–89 years) have now been followed for 5.8 ± 3.3 years. Thirty percent of the female population (n = 35) were taking estrogen-replacement therapy. Subjects were recruited from a population base numbering approximately 950, consisting of relatives, caregivers, and friends of out-patients with stroke and dementia attending our clinic. Motivation for participation was
Results
Fig. 1 displays declining individual CCSE scores in group U and group M+D at baseline and at follow-up (r = −0.20, P < 0.004). Subjects in group M+D (n = 41, ○) developed significant cognitive decline after mean interval of 5.8 (± 3.0) years. Most remained cognitively unchanged (group U, n = 183, •). Cognitive decline occurred predominantly after age 60 (86%); however, 58% of group U were over age 60 (χ2 = 11.5, P < 0.001).
Fig. 2 illustrates regression analyses correlating age at entry with
Discussion
Age-related cerebral degenerative changes are coupled with decreased perfusion, usually assumed to be secondary to decreased cerebral metabolic demands [15], [27], [35], [38], [43], [53], [54], [66]. During aging declines in cerebral tissue densities in gray (polio-araiosis) and white matter (leuko-araiosis) reflect neuronal degenerative changes, which progress concurrent with cerebral perfusion declines. Rates of polio- and leuko-araiosis accelerate geometrically after age 60, correlating with
Acknowledgements
This research was supported by Department of Veterans Affairs Central Office (Washington, D.C.); Harry K. Smith; and the Gordon and Mary Cain Foundation (Houston, TX, USA). James Simon, CRT provided technical assistance during CT scanning; Gerald Timpe and Zihong Zhang, Ph.D., of Diversified Diagnostic Products (Houston, TX, USA) collaborated with providing the xenon enhancer and computer programming for CT-CBF measurements.
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