Executive deficits and regional brain metabolism in Alzheimer's disease.

OBJECTIVE: Executive deficits are common in patients with Alzheimer's disease (AD), contribute prominently to clinical disability, and may be associated with frontal lobe pathology. This study examined regional brain hypometabolism associated with executive dysfunction in patients with AD. METHODS: Forty-one patients with probable AD underwent [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at rest. Neuropsychological measures of executive control included the Conceptualization (Conc) and Initiation/Perseveration (I/P) subscales of the Mattis Dementia Rating Scale (DRS), the Wechsler Adult Intelligence Scale (WAIS) Similarities subtest, the Tower test, and the Ruff Figural Fluency test (Ruff). Voxel-based analyses were conducted using statistical parametric mapping (SPM2) to measure the correlation between regional cerebral metabolism and executive measures. Correlations independent of global cognitive impairment were identified by including Mini-Mental State Examination (MMSE) score as a covariate in the model. RESULTS: Executive deficits, as measured by poor performances on the DRS I/P and Conc subscales, were associated with hypometabolism in the bilateral mid-dorsolateral frontal region. Activity in posterior cortical regions also contributed uniquely to some aspects of executive functioning, as lower resting metabolism in parietal or temporal cortex was correlated with poor performance on four of the five executive measures. After controlling for global cognitive score, there were significant extra-frontal correlations with hypometabolism in insula, occipital lobe, and temporal cortex. CONCLUSIONS: Some but not all executive deficits in AD are associated with neural activity in the dorsolateral frontal cortex. Activities in distributed neural systems that include parietal and temporal cortex also contribute to some executive abilities. The pathophysiology of executive dysfunction is complex and includes abnormalities not limited to a single region.

The neural correlates of naming and fluency deficits in Alzheimer's disease: an FDG-PET study.

OBJECTIVE: To examine the neural processes associated with language deficits in Alzheimer's disease (AD), and in particular to elucidate the correlates of confrontation naming and word retrieval impairments. METHODS: Sixty patients with probable AD were included. Confrontation naming was assessed using the number of words spontaneously named correctly on the Boston Naming Test. We recorded the number of additional words stated following phonemic cuing. We also assessed phonemic (FAS) and semantic (supermarket items) fluency. We then correlated performance on each measure with resting cortical metabolic activity using FDG-PET images. RESULTS: We found that poorer ability to spontaneously name an object was associated with hypometabolism of bilateral inferior temporal lobes. In contrast, when a phonemic cue was provided, successful naming under this condition was associated with higher metabolic activity in bilateral inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), left temporal, and occipital regions. Consistent with these findings, we found that poorer semantic fluency was associated with hypometabolism in regions including both IFG and temporal regions, and poorer phonemic fluency was associated with hypometabolism in only left IFG. Across analyses, measures that required cued retrieval were associated with metabolism in the left IFG, whereas measures taxing semantic knowledge were associated with metabolic rate of left temporal cortex. CONCLUSIONS: Naming deficits in AD reflect compromise to temporal regions involved in the semantic knowledge network, and frontal regions involved in the controlled retrieval of information from that network.