Normal human aging: factors contributing to cerebral atrophy
Introduction
The purpose of the present study was to determine risk factors during uncomplicated aging that accelerate cerebral atrophy and other degenerative changes predisposing to dementia. Since Alzheimer and Binswanger proposed the concept of `arteriosclerotic brain degeneration', evolutionary thinking has followed regarding the nature of vascular dementia (VAD) and admixtures of it with Alzheimer's type of dementia (DAT) (Desmond, 1996). A number of reports have correlated progressive age-related cerebral atrophy with decreased cerebral metabolic demands, which lead to secondary perfusional declines and are associated with the cognitive impairments measured among patients with dementias of both DAT and VAD types (Albert et al., 1984; Barclay et al., 1984; De Leon et al., 1989; Burns et al., 1991; Martin et al., 1991; DeCarli et al., 1992; Obara et al., 1994). Similar studies, among aging normal subjects, report milder progressions of cerebral atrophy, with declines in cerebral metabolism and perfusion. These atrophic changes may predispose to cognitive impairments, since advancing age is well-documented to be the single most important risk factor for dementia (Kety, 1956; Earnest et al., 1979; Kazniak et al., 1979; Schwartz et al., 1985; Meyer et al., 1994, Meyer et al., 1995a; Shear et al., 1995; Waldemar, 1995).
Knowledge of risk factors, other than aging, contributing to cerebral atrophic and degenerative changes are relevant, since these cerebral changes are identifiable by neuroimaging and may be biological markers for depleted neuronal synaptic reserves, predisposing to DAT and VAD (Desmond, 1996; Lancet Conference Writing Committee, 1996; Loeb and Meyer, 1996).
Most studies of age-related cerebral atrophy have utilized cross-sectional designs. Combining cross-sectional with longitudinal designs, utilizing standard CT measures, makes it possible to determine rates of cerebral atrophy, tissue hypodensities and local perfusional declines. These can then be correlated with potential risk factors which may accelerate the process. We evaluate here effects of advancing age, gender, education, history of transient ischemic attacks (TIAs), hypertension, heart disease, hyperlipidemia, diabetes mellitus, smoking, alcohol consumption, closed head injury, post-menopausal estrogen replacement and family histories of cerebrovascular and neurodegenerative disorders (Mortel and Meyer, 1995b, Mortel and Meyer, 1996) which may exacerbate these cerebral atrophic and degenerative changes among initially neurologically and cognitively intact subjects.
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Subjects
Normal volunteers were recruited by published methods, before admission to the study, after signing informed consent (Meyer et al., 1994, Meyer et al., 1995a). Normal volunteers were admitted in sequence if they met the criteria mentioned below and only those not meeting criteria were excluded. Standardized criteria were utilized for determining normal neurological and cognitive status (Meyer et al., 1995a). Ninety-four (94) neurologically and cognitively normal volunteers were followed (Table 1
Results
Prevalence of hyperlipidemia was greater among TIAs subjects, and alcohol consumption was greater among subjects without TIAs (Table 1). At entry, neuropsychological testing fell within normal limits among all subjects, and remained so at final testing, except among three older female volunteers. Their mean age was 74.0±11.0 years, range 63–85. Their mean CCSE scores declined 4.4 points, from 27.7 to 23.3, which is clinically significant. Of the three, one had hypertension, two had
Discussion
The present study confirms the well-known coupling of age-related cerebral atrophy with decreased cerebral perfusion (Kety, 1956; Earnest et al., 1979; Kazniak et al., 1979; Schwartz et al., 1985; Martin et al., 1991; Meyer et al., 1994, Meyer et al., 1995a; Shear et al., 1995; Waldemar, 1995). Results indicate: that polio- and leuko-araiosis progress concurrently. Rates of leuko-araiosis double after age 60, correlating with progressive cortico-subcortical atrophy and ventricular enlargement.
Acknowledgements
This research work was supported by the Department of Veterans Affairs, Central Office, Washington, DC; Gordon and Mary Cain Foundation, Houston, Texas. James Simon, CRT provided technical assistance during CT scanning. Gerald Timpe and Zihong Zhang, Ph.D. of Diversified Diagnostic Products, 11603 Windfern, Houston, TX 77064, USA, provided the Xenon Enhancer, and computer programming for CT-CBF measurements.
References (44)
- et al.
The effect of advanced old age on the neurone content of the cerebral cortex. Observations with an automatic image analyzer point counting method
J. Neurol. Sci.
(1983) - et al.
Computed tomography in Alzheimer's disease: A longitudinal study
Biol. Psychiat.
(1991) Human cerebral blood flow and oxygen consumption as related to aging
J. Chron. Dis.
(1956)- et al.
Vascular dementia: still a debatable entity?
J. Neurol. Sci.
(1996) - et al.
CT changes associated with normal aging of the human brain
J. Neurol. Sci.
(1994) - et al.
Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type
J. Neurol. Sci.
(1994) - et al.
15-year longitudinal study of blood pressure and dementia
Lancet
(1996) - et al.
Ventricular size in patients with presenile dementia of the Alzheimer's type
Arch. Neurol.
(1984) - et al.
Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors
Stroke
(1986) - et al.
Rates of decrease of cerebral blood flow in progressive dementias
Neurology
(1984)
Neural apoptosis
Ann. Neurol.
Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomography scans
Science
Apoptosis and necrosis after reversible focal ischemia: An in situ DNA fragmentation analysis
J. Cereb. Blood Flow Metab.
Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type
Neurology
Alzheimer's disease: longitudinal CT studies of ventricular change
Am. J. Neuroradiol.
Vascular dementia: a construct in evolution
Cerebrovasc. Brain Metab. Rev.
Cortical atrophy, ventricular enlargement and intellectual impairment in the aged
Neurology
Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies
Am. J. Neuroradiol.
Leuko-araiosis
Arch. Neurol.
Vascular risk factors and leuko-araiosis
Arch. Neurol.
Cerebral atrophy, EEG slowing, age, education, and cognitive functioning in suspected dementia
Neurology
The theory and applications of the exchange of inert gas at the lungs and tissues
Pharmacol. Rev.
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