Gray-Matter Degeneration in Presenile Alzheimer's Disease

Previous comparisons between presenile Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) did not control for disease severity and duration. In the current study, 18 patients with each diagnosis were matched for disease duration, cognitive dysfunction, and behavioral symptoms (using the modified Mini-Mental Status [mMMS] examination and the Blessed Dementia Rating Scale [BDRS]). Regional cerebral blood flow (rCBF) was quantified by the 133xenon inhalation technique, and several indices of tissue perfusion were examined. The two variables of primary interest were relative gray-matter weight and a gray-matter perfusion index, the initial slope index. Presenile onset was associated with loss of gray-matter relative weight (35% in presenile patients versus 39% in senile patients and healthy control subjects, p = 0.006), with neither perfusion nor disease severity differences between the two dementia samples. This loss of gray matter was significantly related to both severity and duration of disease in the patients with presenile AD, but not in patients with SDAT. These findings lend support to previous suggestions of greater degenerative process in presenile AD and confirm the need to examine and control age of onset in future investigations of AD. Further, correlation analysis suggests greater proportion of common variance among clinical and physiological indices in presenile AD

Regional Cerebral Blood Flow in Mood Disorders. II. Comparison of Major Depression and Alzheimer's Disease

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression,30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and AIzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subproflle Model,developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning

Relationship between Lifetime Occupation and Parietal Flow: Implications for a Reserve against Alzheimer's Disease Pathology

We previously reported an inverse relation between parietal cerebral blood flow and years of education in Alzheimer's disease (AD) patients matched for clinical severity. This suggested that the clinical manifestation of advancing AD pathology is delayed in patients with higher educational attainment. Other aspects of life experience may also provide a reserve against the clinical expression of AD. To test this hypothesis, we classified the primary lifetime occupations of 51 AD patients using the Dictionary of Occupational Titles, published by the US Department of Labor, and derived six factor scores describing intellectual, interpersonal, and physical job demands. Regional cerebral blood flow was measured using the xenon-133 inhalation method. After controlling for age, clinical dementia severity, and education, there was less relative perfusion in the parietal region in subjects whose occupations were associated with higher interpersonal skills and physical demands factor scores. We conclude that independent of education, aspects of occupational experience may provide a reserve that delays the clinical manifestation of AD

Cerebral Single-Photon Emission Computed Tomography Abnormalities in Human Immunodeficiency Virus Type 1-Infected Gay Men without Cognitive Impairment

Objective: To determine whether technetium Tc 99m exametazime single-photon computed emission tomography (SPECT) can distinguish gay human immunodeficiency virus (HIV)—positive subjects, both with and without mild cognitive impairment, from gay HIV-negative control subjects. Design: Twenty HIV-positive subjects (12 without cognitive impairment and eight with mild cognitive impairment) and 10 HIV-negative subjects underwent neurological, neuropsychological, magnetic resonance imaging, and technetium Tc 99m exametazime SPECT examinations. Setting: Subjects were recruited from a natural history study of gay men with HIV infection. Patients: Subjects from the cohort who had previously participated in a magnetic resonance imaging study were selected for the SPECT study. Main Outcome Measures: The SPECT scans were rated as abnormal if focal defects, confirmed by a horizontal profile analysis, were seen. Results: Sixty-seven percent of HIV-positive subjects without cognitive impairment, 88% of HIV-positive subjects with mild cognitive impairment, and 20% of HIV-negative subjects had abnormal SPECT scans (P<.05 for both HIV-positive groups when each group was compared with HIV-negative subjects). Conclusion: Compared with gay HIV-negative control subjects, focal SPECT defects are seen with an increased frequency in HIV-positive gay men without cognitive impairment and in HIV-positive gay men with mild cognitive impairment

99mTc Hexamethyl-Propylene-Aminoxime Single-Photon Emission Computed Tomography Prediction of Conversion From Mild Cognitive Impairment to Alzheimer Disease

Objective—To examine the utility of single photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)

WAIS-R Subtest Profile and Cortical Perfusion in Alzheimer's Disease

WAIS-R profiles were investigated in 28 Alzheimer′s disease (AD) and 21 healthy elderly subjects. The Fuld subtest profile, previously reported to have potential as a diagnostic marker for AD, was observed in 35.7% of our AD patients and 4.8% of the controls. We compared AD patients with the Fuld profile (ADF+) to a group of patients without the profile (ADF−) with similar demographics and dementia severity and demographically matched normals using regional Cerebral Blood Flow. Both AD groups showed reduced blood flow in the parietotemporal cortex compared to normals, but the ADF+ patients had greater flow reductions than the ADF− group. Examination of WAIS-R performance indicated that the ADF+ group had lower scores than the ADF− patients on the Digit Symbol and Block Design subtests, and further, that these two subtests were associated with the parietotemporal perfusion deficit in our AD sample. Our findings do not support the use of the Fuld profile as a diagnostic marker for AD, but do provide physiological evidence for behavioral heterogeneity among AD patients based on WALS-R subtest performance

Inferior Parietal Perfusion, Lateralization, and Neuropsychological Dysfunction in Alzheimer's Disease

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting133Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence, verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and—paradoxically—verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predictive of cognitive decline in AD. Right-sided deficits, however, may be most important for predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline as measured by most standard neuropsychological measures