Katsuyuki Obara

Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type.

Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are +9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus -2.5 ml, total white matter -0.6 ml, frontal white matter -0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007).

CT changes associated with normal aging of the human brain

CT was used to measure changes in cerebral gray and white matter tissue densities associated with normal aging, using a cross-sectional design, in order to provide normative data for comparisons with abnormal aging such as dementias of Alzheimers and vascular types. Cerebral compartmental densities were measured using plain CT, and their perfusion values were recorded during stable xenon inhalation (CT-CBF), among 81 neurologically and cognitively normal volunteers of different ages. Results led to the conclusion that cortical gray matter tissue densities progressively decline (polio-araiosis) after age 60. Cortical polio-araiosis is coupled with regional hypoperfusion but not with cortical atrophy. It is speculated that the cortical hypodensity identified by CT imaging parallels declines in cortical synaptic density, as reported from autopsy studies using anti-synaptophysin staining of cerebral cortex obtained from normal people above and below age 60. The coupling of cortical hypoperfusion with polio-araiosis is believed to reflect age-related reductions of cortical metabolic demands as reported by PET. During normal aging leuko-araiosis correlates directly with cortical atrophy, suggesting that anterograde axonal degeneration resulting from cortical neuronal dearborization play a role in its causation.

Leuko-araiosis and cerebral perfusion in normal aging

To clarify the incidence, age relationships and pathogenesis of white matter lesions of unknown origin (leuko-araiosis) detected by neuroimaging among normal elderly volunteers, we measured the severity of leuko-araiosis using computerized tomographic (CT) densitometry among 42 healthy self-supporting men and women of different ages, all with normal neurological and cognitive test performance. Results were correlated with local cerebral perfusion using xenon-contrasted CT. The 42 volunteers, who are followed in this laboratory for studies of normal aging, were divided into two groups in order to determine aging effects by an extremes design. One group consisted of 19 adults below age 60 (M = 53.3, SD = 6.0). The index group comprised 23 individuals all over the age of 60 (M = 71.6, SD = 8.7). Leuko-araiosis around the anterior horns of the lateral ventricles (frontal leuko-araiosis) was more severe (p < .01) among the older group, however, occipital leuko-araiosis did not significantly differ between older and younger groups. Cerebral perfusion in frontal, temporal, and parietal cortex was decreased among older compared with younger volunteers (ps < .001, .01, and .05, respectively). Multiple regression analyses disclosed significant and direct relationships between severity of frontal leuko-araiosis and (a) frontal cortical atrophy and (b) reductions of cerebral perfusion within frontal white matter and caudate nucleus. We conclude that cortical atrophy with hypoperfusion and ischemia of frontal white matter play a part in the pathogenesis of frontal leuko-araiosis associated with normal aging and this may be a predictor for later cognitive declines.

Cognitive Performance after Small Strokes Correlates with Ischemia, Not Atrophy of the Brain

Computerized tomographic measures of recurrent cerebral infarctions, atrophy and local perfusion were all prospectively correlated with cognitive testing during treatment of risk factors plus antiplatelet therapy among vascular dementia patients. Neurological and cognitive status were quantified among 22 demented patients with small strokes and compared with 22 age-matched normal volunteers. In vascular dementia, risk factor control plus antiplatelet therapy reduced cerebral infarctions, increased perfusion, and stabilized or improved cognitive test performance, despite age-related, progressive cerebral atrophy.

Problems Encountered with Longitudinal Neurological, Psychometric and Cerebral CT Imaging among Stroke Data Bank Patients with Dementia

41 patients (30 men, 11 women, mean age 65.3 +/- 9.7 years) with probable ischemic vascular dementia diagnosed according to stated clinical criteria at least 3 months after hospital discharge and among a few nonhospitalized subjects with thorough clinical, neurovascular and neuroimaging workup have been followed for the past 7 years with serial measures of neurological and cognitive status and cerebral blood flow using stable xenon-enhanced CT. Cognitive impairments correlated with cerebral ischemia rather than CT measurements of infarcted brain volume. A minimum of one follow-up was required and follow-up intervals ranged from 4 months to 6.6 years (mean 3.4 +/- 1.6 years). 9 patients (22.0%) were lost to follow-up, 4.9% died, 9.8% became incapacitated by additional strokes, 2.4% by cancer and 4.9% moved away. Cross-sequential designs adjust for problems of attrition. Mortality rates of 1.4%/year during 1986-1993 are significantly lower than 2.0%/year between 1983 and 1986. Declines in mortality are attributed to control of risk factors and antiplatelet treatment of atherosclerotic cerebral vascular disease and anticoagulant treatment of patients with cardiogenic embolism.

Lacune-associated cerebral hypoperfusion correlates with cognitive testing

The hypothesis was tested among 83 patients with multiple lacunar infarctions that cerebral hypoperfusion will correlate with cognitive impairments. Patients were subdivided according to Cognitive Capacity Screening Examination (CCSE) scores into a cognitively impaired group (Group D, n = 40; mean age, 68.2 years) with CCSE scores between 6 and 25 (mean, 19.9) and a cognitively intact group (Group I, n = 43; mean age, 66.0) with normal scores (mean, 29.4). Gray and white matter tissue densities were measured by plain computed tomography (CT), and their compartmental perfusions were estimated during stable xenon inhalation. Eighty infarcts in basal ganglia and white matter were detected in Group D and 62 in Group I. Cognitive impairments correlated with (a) multiplicity and bilaterality of lacunes; (b) hypertension, diabetes mellitus, and multiplicity of risk factors for stroke; (c) hypoperfusion of white and gray matter, but particularly of frontal white matter; (d) leuko-araiosis; (e) aging; and (f) lower education. The conclusion was that hypertension and diabetes mellitus are potent risk factors for cerebral small vessel disease or arteriolosclerosis ultimately resulting in lacunar infarcts, leuko-araiosis, white matter hypoperfusion, and impaired cognitive test performance.

Cerebral density and perfusion measured among heart disease patients with and without stroke.

This investigation was designed to clarify the chronic effects of cardiogenic emboli on cerebral perfusion and tissue densities within remaining noninfarcted brain. Local cerebral perfusion and tissue densities were measured by xenon-contrasted CT scanning and compared by cross-sectional designs among normal volunteers without heart disease (Group C, n = 44), normal volunteers with heart disease (Group N, n = 20), patients with heart disease and lacunar infarctions (Group L, n = 31) and patients with heart disease associated with cardiogenic cerebral embolism (Group E, n = 12). In Group E, remaining cortical and subcortical gray and white matter perfusion were reduced compared to Groups C and N (p = 0.01), but did not differ from Group L, who had similar profiles of risk factor for stroke. In Group E, perfusion was reduced within the thalamus ipsilateral to cortical infarctions (p < 0.05). There were no differences in remaining tissue densities between Groups E and L. It is concluded that reduced cerebral perfusion in noninfarcted regions among patients with cardiogenic emboli appears to be related to atherosclerosis of small cerebral vessels in a similar manner to patients with lacunes, but thalamo-cortical disconnections also contribute to cerebral hypoperfusion.

Prospective Measures of Cerebral Atrophy and Perfusion Among Cognitively Intact Stroke Patients

Cerebral atrophy, tissue densities, and local perfusions were measured prospectively utilizing computed tomography among 19 cognitively intact stroke patients and 24 age-matched cognitively and neurologically normal controls. Mean follow-up intervals were 27.0 months for stroke patients and 31.0 months for controls. Stroke patients were treated by controlling risk factors and antiplatelet drugs. Cognitive testing remained normal among patients and controls. Among stroke patients, annual rates for cerebral atrophic indices were +3.4%, for ventricular enlargement +6.9%, for subarachnoid space enlargement +0.1%, and for cortical atrophy -2.5%. Annual reductions in cerebral perfusion, per 100 g brain/min, for cortex were total, -2.3 ml; frontal -3.8 ml; temporal, -2.4 ml; occipital, 2.0 ml; basal ganglia, -2.3 ml; and thalamus -3.8 ml. Annual decreases in local Hounsfield unit (LHU) densities for cortex were total, -0.6 HU; frontal, -0.8 HU; and temporal, -0.4 HU. Among controls, annual rates for cortical atrophy were -1.0% and for declines in cerebral perfusion were -0.7 ml for total cortex, and -1.4 ml for temporal cortex. Annual decreases in HU densities were total cortex, -0.6 HU; frontal, -0.9 HU; and temporal -0.4 HU. Among cognitively intact stroke patients, annual rates for cerebral atrophy and reductions in cerebral cortical perfusion were accelerated by more than three times those seen among agematched controls but were significantly less than similar measures among stroke patients with dementia.