Intellectual decline predicts the parietal perfusion deficit in Alzheimer's disease

The pathophysiology of Alzheimer's disease may be reflected more in an individual's decline from premorbid levels of functioning than in current measures of absolute severity. To test this hypothesis, we computed an index of intellectual decline for individual patients and examined its relationship to Alzheimer's disease-related functional brain abnormalities.

We studied 27 patients with Alzheimer's disease diagnosed by ADRDA-NINCDS criteria. We used patient demographics and published formulas to construct estimates of premorbid Wechsler Adult Intelligence Scale (WAIS-R) IQs for each subject in the sample and used a current IQ assessment to estimate the decline in IQ that occurred during the disease for each subject. Cortical perfusion was quantified by the planar 133Xe regional cerebral blood flow (rCBF) technique. The characteristic abnormality in parietal cortex was expressed by the parietal index (PI).

Over the estimated disease duration of 3.8 +/- 2.2 yr, the full-scaled IQ declined by an estimated 28.0 +/- 15.5 points. The current PI was in turn well correlated with the IQ decline (r = 0.66; p < 0.001). This association was linear and stronger than those with other, more common measures of current severity. A multiple stepwise regression analysis suggested that IQ decline alone accounted for the variance in PI related to clinical deterioration. Actual images showed a mild blood flow deficit in patients with the smallest estimated IQ declines but deep and extensive lesions in patients with large declines.

These results suggest that the decline from the premorbid baseline, rather than current level of functioning, best predicts the extent of brain damage reflected in the rCBF abnormality, a finding independent of demographic variance.