Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers.

OBJECTIVE: Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. METHOD: Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function. RESULTS: Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks. CONCLUSIONS: Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.

Word list generation performance in Alzheimer's disease and vascular dementia.

Word list generation (WLG) was examined among clinical samples of individuals with Alzheimer's disease (AD) (n = 73) or ischemic vascular dementia (IVD) (n = 85), equivalent in age, education, current and estimated premorbid intellectual functioning, and proportion of men and women. The AD group performed significantly better than did the IVD group on lexical WLG, and a trend was observed indicating superior performance among the IVD group on categorical WLG. Within-groups, comparisons of group means, and profile analyses of individual performance patterns all indicated that persons with AD demonstrated a lexical > categorical pattern significantly more often than did IVD participants. The absolute difference in average performance between the AD and IVD groups on lexical and categorical WLG was small; the findings, however, generally support the clinical utility of the lexical > categorical WLG pattern in the differential diagnosis of AD and IVD. The patterns of performance support the presence of relative impairment in semantic processing among the individuals with AD and global deficits in retrieval and processing speed in individuals with IVD.