Mentis, M. J., Alexander, G. E., Furey, M. L., Levine, B., Prasad, K., Krasuski, J., Pietrini, P., Schapiro, M. B., & Rapoport, S. I. (1997). Effect of dementia severity on the functional response to parametric visual stimulation during PET in Alzheimer disease. NeuroImage, 5(4 PART II), S343.
Mentis, M. J., Alexander, G. E., Grady, C. L., Horwitz, B., Krasuski, J., Pietrini, P., Strassburger, T., Hampel, H., Schapiro, M. B., & Rapoport, S. I. (1997). Frequency variation of a pattern-flash visual stimulus during PET differentially activates brain from striate through frontal cortex. NeuroImage, 5(2), 116-128.
PMID: 9345542;Abstract:
We evaluated regional cerebral blood flow (rCBF) in 19 healthy elderly subjects, mean age 64 ± 11 (SD, years), during a passive visual stimulus in which pattern-flash frequency was parametrically manipulated. Using goggles with a grid of red lights imbedded into each lens, we performed five positron emission tomography (PET) H215O water scans on each subject at alternating (left to right eye) flash frequencies of 0, 1, 4, 7, and 14 Hz. We found a biphasic rising and falling rCBF response in the striate cortex (7 Hz peak) and left anterior cingulate (4 Hz peak), 1 Hz activation in left middle temporal gyrus (V5), monotonically increasing rCBF in posterior areas (lateral and inferior visual association areas, Brodmann 18 and 19), and monotonically decreasing rCBF in anterior areas (frontal, cingulate, and superior temporal) predominantly in right hemisphere. We suggest the striate rCBF changes at all frequencies primarily reflect lateral geniculate input, the middle temporal activation at 1 Hz reflects perception of apparent motion, and the posterior extrastriate rCBF monotonic increase represents a neural response to increasing luminance intensity and form and color complexity that occur as pattern-flash frequency increases. The anterior monotonic rCBF decrease may represent active cross-modal functional suppression of brain areas irrelevant for processing the passive visual stimulus. Pattern-flash rCBF responses were highly reproducible (no series effect), more so in posterior than in anterior brain regions. The reproducibility and systematically changing rCBF responses to this passive stimulus suggest that it could be successfully used as a disease probe to evaluate neural function and drug effects in cognitively impaired patients.
Ewers, M., Walsh, C., Trojanowski, J. Q., Shaw, L. M., Petersen, R. C., Jack, C. R., Feldman, H. H., Bokde, A. L., Alexander, G. E., Scheltens, P., Vellas, B., Dubois, B., Weiner, M., & Hampel, H. (2012). Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance. Neurobiology of Aging, 33(7), 1203-1214.e2.
PMID: 21159408;PMCID: PMC3328615;Abstract:
The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ1-4 ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects. © 2012 Elsevier Inc.
Pietrini, P., Furey, M. L., Alexander, G. E., Mentis, M. J., Dani, A., Guazzelli, M., Rapoport, S. I., & Schapiro, M. B. (1999). Association between brain functional failure and dementia severity in Alzheimer's disease: Resting versus stimulation PET study. American Journal of Psychiatry, 156(3), 470-473.
PMID: 10080567;Abstract:
Objective: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. Method: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. Results: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. Conclusions: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest.
Acklin, M. W., Sauer, A., Alexander, G., & Dugoni, B. (1989). Predicting depression using earliest childhood memories. Journal of Personality Assessment, 53(1), 51-59.
