Faculty Bibliography

The most widely known substances that have been investigated for treating cognitive deterioration in the aged are cerebral vasodilators, Gerovital H3, psychostimulants, 'nootropics,' neuropeptides, and neurotransmitters. The rationale for the choice of specific agents has shifted as our conceptions regarding the origins of cognitive decline have changed; we now know that most cognitive deterioration occurs independently of arteriosclerotic vascular changes. Substances currently being investigated because of their effects on brain electrophysiology, on neurohumoral processes, or on central neurotransmitters show promise

(18)F-2-deoxy-2-fluoro-D-glucose ((18)FDG) is a positron emitting tracer for rate of glucose utilization in brain. When used in conjunction with positron emission tomography (PET), the PET-FDG technique permits in vivo quantitation of regional brain metabolism in man. We have applied this technique to the study of regional brain function in normal aging and senile dementia. Preliminary results for 7 patients with senile dementia of the Alzheimer's type (SDAT) and 3 elderly normal subjects indicated a large, statistically significant (p < 0.01) diminution in rate of glucose utilization in SDAT. Furthermore, the degree of diminution in metabolic activity in SDAT was highly correlated with objective measures of degree of cognitive impairment. These results demonstrate the feasibility and potential utility of the PET-FDG technique for studying regional brain function in normal aging and dementia.

Neuropathological investigations have demonstrated brain-behavior relationships in senile dementia of the Alzheimer's type (SDAT), but CT studies have not produced consistent findings. We hypothesized that these discouraging results were in part due to limitations in the methods of CT scan evaluations, and to non-homogeneity of patient populations. The present study examined 43 out-patients with the presumptive diagnosis of SDAT using 37 cognitive test measures and 3 independent CT evaluation strategies. The CT methods included a new rank ordering procedure and two previously used techniques, physical measurement and 4-point rating. Highly significant (p less than or equal to 0.01) brain-behavior correlations were attained using the ranking and rating procedures for evaluation of ventricular and cortical pathology. It was found that rank ordering has high interrater reliability and is superior to the other methods for the evaluation of the ventricular system. The physical measurement of the third ventricle is the single most powerful linear correlate of cognitive impairment. Measurement of cortical sulci are of no correlational significance. Multiple regression analyses indicated that global assessments are the best cognitive predictors of both ventricular and cortical pathology. Thus the present study has demonstrated brain-behavior relationships in vivo in SDAT.