To determine the effects of MRI white matter hyperintensities (WMH) on cognitive functioning, we used neuropsychologic tests and MRI to study 150 elderly volunteers free of neuropsychiatric or general disease. There were 76 (50.3%) individuals without and 74 (49.7%) with WMH. The latter subset was older (61.3 +/- 6.6 years versus 58.5 +/- 5.8 years, p = 0.005), had a higher mean arterial blood pressure (103.7 +/- 11.4 mm Hg versus 99.9 +/- 10.3 mm Hg, p = 0.03), and a larger ventricular-to-intracranial-cavity ratio (6.3 +/- 5.6% versus 4.7 +/- 1.6%, p = 0.02). Individuals with WMH performed worse than their counterparts without such abnormalities on all tests administered. After adjusting for the group differences in age, arterial blood pressure, and ventricular size, we noted statistically significant results on form B of the Trail Making Test (121.8 +/- 37.8 msec versus 100.3 +/- 47.9 msec, p = 0.04), a complex reaction time task (680.8 +/- 104.9 msec versus 607.1 +/- 93.9 msec, p = 0.001), and the assembly procedure of the Purdue Peg-board Test (27.5 +/- 5.8 versus 30.6 +/- 5.9, p = 0.02). Partial correlations did not reveal any relationship between test scores and the semiautomatically assessed total area of WMH. Our data suggest that the presence of WMH exerts a subtle effect on neuropsychologic performance of normal elderly individuals, which becomes particularly evident on tasks measuring the speed of more complex mental processing.

We administered the Mattis Dementia Rating Scale (MDRS) to 1,001 healthy volunteers, aged 50 to 80 years, randomly selected from our community. Multivariate regression analysis revealed educational level (p = 0.000004) and age (p = 0.00001), but no other sociodemographic or risk factors for stroke, to be significantly associated with the MDRS score. The age- and education-specific lowest quintile cutoff scores ranged from 140 in subjects aged 50 to 59 years with at least college experience to 130 in subjects aged 70 to 80 years with only 4 to 9 years of schooling. These percentile distributions obtained for decades of age and different levels of education should be useful reference values for clinicians and investigators when applying the MDRS to assess cognitive functioning.

Our study demonstrated an association between estrogen replacement therapy and better cognitive functioning and a lower rate of clinically unsuspected ischemic brain damage in postmenopausal women.

These observations are compatible with the view that some dietary antioxidants may protect against cognitive impairment in older people.

The presence of the apolipoprotein E e4 allele has been considered to be a risk factor for Alzheimer's disease and vascular dementia. We therefore used demanding neuropsychologic testing and brain MRI to determine if elderly normals with at least one e4 allele demonstrate subclinical changes in cognition and a higher frequency of brain atrophy or silent ischemic brain damage. The study population consisted of 214 randomly selected individuals aged 50 to 75 years without neuropsychiatric or general disease. There were 175 (81.8%) subjects without and 39 (18.2%) with at least one e4 allele. The two groups were comparable for age, length of education, verbal intelligence, mood and major vascular risk factors. Apolipoprotein E e4 carriers performed significantly worse than non‐carriers when assessed for learning and memory abilities, while there were no differences in test results of conceptualization, attention, speed of mental processing and visuopractical skills. There were no between‐group differences for thromboembolic and lacunar infarcts, white matter hyperintensity grading and the semiautomatically measured white matter hyperintensity area. The extent of sulcal and ventricular widening as well as hippocampal and parahippocampal volumes were also similar between the comparative subsets. We conclude that the apolipoprotein E e4 allele is associated with subtle learning and memory deficits in normal elderly persons and may therefore be suggested a marker for accelerated cognitive aging. In this group of subjects it was not associated with brain parenchymal changes as demonstrated by MRI.