Randomized clinical trial of daily aspirin therapy in multi-infarct dementia. A pilot study.

Seventy multi-infarct dementia patients were randomized into an aspirin-treated group and an untreated control group for an exploratory investigation to determine any effects of 325 mg aspirin daily on cognitive performance. The control group did not receive placebo but evaluations were carried out in a blinded manner. The index group (N = 37, mean age 67.1 years) received 325 mg of aspirin by mouth once daily while the control group (N = 33, mean age 67.6 years) was followed and treated in a similar manner except that they received no aspirin. Both groups had comparable risk factors for stroke, which were treated similarly, as well as comparable initial cerebral blood flow values, as measured by the 133xenon inhalation method, and initial scores on Cognitive Capacity Screening Examination testing. Patients were evaluated at intervals of one year. Significant improvements were demonstrated for cerebral perfusion values (P less than .0001) and cognitive performance scores (P less than .0001) among aspirin-treated patients compared to untreated controls at each of three annual follow-up evaluations. Both men and women benefited from aspirin therapy and their quality of life and independence appeared to be improved, which was not apparent in the control group. Daily aspirin appears to improve or stabilize declines in cerebral perfusion and cognition among patients with multi-infarct dementia.

Reducing hypertriglyceridemia in elderly patients with cerebrovascular disease stabilizes or improves cognition and cerebral perfusion.

Effects of lowering serum triglyceride levels were investigated among 44 elderly hypertriglyceridemic patients with risk factors for stroke, reduced cerebral perfusion, and a history compatible with symptomatic occlusive cerebrovascular disease. Patients were randomly assigned to either treatment with gemfibrozil, a lipid-lowering agent, or control conditions. Subjects in both groups were instructed to follow a diet recommended for lowering serum lipid levels, while the treatment group was additionally administered 600 mg daily of gemfibrozil. Subjects assigned to the treatment group (n = 22) showed significant reductions in serum triglyceride levels (p less than .0005). Control subjects (n = 22) did not show any significant changes in serum triglyceride levels. There were also no significant changes in total cholesterol levels in either group. Analyses of values for mean bihemispheric gray matter cerebral blood flow measured by the xenon 133 inhalation method and cognitive scores tested by the Cognitive Capacity Screening Examination indicated that gemfibrozil-treated patients maintained significantly higher levels of cerebral perfusion and cognitive performance than untreated controls did. Regression analyses for different treatment intervals indicated that both cerebral blood flow and cognition showed linear improvements that correlated directly with the duration of treatment. Lowering triglyceride levels in hyperlipidemic subjects appears to benefit cerebral perfusion and cognitive performance after four to six months.

Aetiological considerations and risk factors for multi-infarct dementia.

One hundred and seventy five multi-infarct dementia (MID) patients were evaluated for risk factors for stroke as well as for the types of cerebrovascular lesions that were present. The incidence of associated risk factors for stroke were as follows: hypertension (66%), heart disease (47%), cigarette smoking (37%), diabetes mellitus (20%), moderate alcohol consumption (19%) and hyperlipidaemia (21%). The most frequently occurring type of lesions were multiple lacunar infarctions of the brain (43%). These were combined with other types of stroke in an additional 21%. Atherosclerotic occlusive disease of the carotid and vertebrobasilar arteries occurred alone in 18% and was associated with other types of stroke in another 25%. Embolic cerebral infarctions were present alone in 8% and were combined with other types of stroke in 15%. MID was more frequent in men (62%) than women (p less than 0.002). Mean bihemispheric gray matter cerebral blood flow (CBF) values showed a fluctuating course and when results were pooled and compared between different types of MID, extracranial occlusive disease and/or multiple lacunar infarctions resulted in lowest CBF values. The location of cerebral infarctions was more importantly related to cognitive impairments than was the total volume of infarcted brain. Mortality rates among 125 MID patients followed for 31 months has been 5%. Correct clinical classification of the types of cerebrovascular lesions was confirmed in three necropsied cases.

Diabetes mellitus as a risk factor for stroke.

To evaluate the relative potency of diabetes mellitus as a risk factor for stroke, the relative frequency of stroke symptoms was compared among cohorts with and without diabetes. Stroke symptoms were classified as atherothrombotic cerebral infarctions, transient ischemic attacks, reversible ischemic neurologic deficits, and multi-infarct dementia. The groups were compared according to the occurrence of these symptoms, and both cross-sectional and longitudinal designs were used to study 293 consecutive patients referred to this laboratory and to contrast groups with and without diabetes. Hypertension, heart disease, and stroke symptoms and signs were more frequent among diabetics than among age-matched nondiabetics. Among diabetics, strokes occurred at an earlier age and were more common among men. Regression analyses assigned diabetes second to hypertension as a risk factor for stroke, followed by heart disease and smoking. Diabetes associated with hypertension or hyperlipidemia added significantly to stroke risk. Initially, cerebral blood flow values and cognitive test scores were equivalent among diabetics and nondiabetics; after 3 years, cognition became significantly impaired among diabetics, despite better maintenance of cerebral blood flow among treated diabetics compared with nondiabetics. Diabetes acts to compound risk for stroke not only by promoting cerebral atherogenesis but also by aggravating other risk factors including hypertension, heart disease, and hyperlipidemia.