Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease

Verbal ¯uency tasks are used to assess language functioning in Alzheimer's disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of ¯uency tasks was associated with di€erent patterns of cerebral blood ¯ow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood ¯ow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the di€erence between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal ¯ow, a focal AD-related de®cit. Additional variance in Category ¯uency, however, was predicted by global mean ¯ow, while additional variance in Letter Fluency was predicted by frontal ¯ow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean ¯ow; the primary predictor of Letter Fluency was left-sided frontal ¯ow. Analysis of the ¯uency di€erence score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related de®cits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related de®cits were accompanied by marked de®cits in frontal perfusion. These ®ndings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency's stronger association to the most typical CBF de®cits of AD account for its greater sensitivity to this disease. Letter Fluency de®cits, on the other hand, carry signi®cant information about the degree to which perfusion de®cits have spread to frontal cortex. # 1999 Elsevier Science Ltd. All rights reserved