Biomedical subjects

R Mohs

Publications and source records attributed to R Mohs.

23 records · Page 2Linked to original sources

PubMed1993

The consortium to establish a registry for Alzheimer's disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease.

Reliable information on rate of progression of cognitive impairment in probable Alzheimer's disease (AD) is important for evaluating possible beneficial effects of therapeutic agents and in planning long-term care for patients with this chronic illness. However, wide variability exists in published rates of change for psychometric measures of the dementing process, and there is need for an accurate analysis of large numbers of persons with the disorder studied over long periods. Utilizing the large, well-characterized sample of the Consortium to Establish a Registry for Alzheimer's Disease and employing a least squares regression method to adjust for different levels of impairment and periods of observation, we report rates of change on the Short Blessed Test, Mini-Mental State Examination, Blessed Dementia Scale, Clinical Dementia Rating, and other cognitive measures in 430 patients with probable AD (mean age at entry = 70.9 +/- 8.0 SD years) studied for up to 4 years. We found that rate-of-change determinations are less reliable when the observation period is 1 year or less, that dementia progression may be nonlinear when described by certain measures, and that simple change scores do not accurately characterize the rate of decline. We also found that rate of progression in AD is determined by the severity of cognitive impairment: the less severe the dementia, the slower the rate of decline.

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PubMed1991

Detection of abnormal memory decline in mild cases of Alzheimer's disease using CERAD neuropsychological measures.

The present study was designed to determine which of the memory tasks included in the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery best differentiate patients with early Alzheimer's disease from cognitively normal elderly control subjects and also best distinguish between the various levels of severity of the dementia process. A sample of CERAD patients with Alzheimer's disease was stratified by disease severity into those with mild, moderate, or severe dementia and matched with control subjects for sex, age, and education. Using multivariate procedures and cutting scores, the efficacy of each memory measure in distinguishing between these groups and control subjects was determined. The test for delayed recall was found to be the best overall discriminatory measure. The other tests of memory, ie, immediate recall, intrusion errors, and recognition memory, had poor overall discriminability. None of the CERAD memory measures were found to be particularly powerful in staging the severity of dementia. These findings suggest that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.

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PubMedDate not supplied

Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline.

CONTEXT: Alzheimer disease (AD) is characterized neuropathologically by the presence of amyloid beta-peptide (Abeta)-containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of Abeta correlates with dementia and whether Abeta alterations precede or follow changes in tau. OBJECTIVES: To determine whether accumulation of Abeta correlates with the earliest signs of cognitive deterioration and to define the relationship between Abeta accumulation and early tau changes. DESIGN, SETTING, AND PATIENTS: Postmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of Abeta variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia. MAIN OUTCOME MEASURES: Levels of total Abeta peptides with intact or truncated amino termini and ending in either amino acid 40 (A(beta)x-40) or 42 (A(beta)x-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score. RESULTS: The levels of both A(beta)x-40 and A(beta)x-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone A(beta)x-42 peptide were higher than those of A(beta)x-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in A(beta)x-40 and A(beta)x-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease. CONCLUSIONS: In this study, levels of total A(beta)x-40 and A(beta)x-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, Abeta was elevated before the occurrence of significant tau pathology. These results support an important role for Abeta in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.

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PubMedDate not supplied

Elevated serum total and LDL cholesterol in very old patients with Alzheimer's disease.

The relationships of serum lipids with Alzheimer's disease (AD) and other dementias in very old patients are not clear. All residents of an academic nursing home were studied clinically for dementia and for serum lipids. All those autopsied over a 7.7-year period had apolipoprotein E (apoE) genotyping and detailed neuropathological examination. Those with pathologically defined criteria for AD (n = 84) were compared to all others who also had clinical dementia but did not show AD changes (n = 22). In contrast to most other reports of serum lipids in very old patients with AD, total cholesterol (TC) and low density lipoprotein cholesterol levels were each significantly higher for those with AD. The lipid-AD associations were progressively stronger with increasing pathological certainty of AD diagnosis. These relationships remained significant after adjustment for apoE genotype and for other known risk factors. The lipid-AD associations in a very old cohort, and prior evidence that elevated TC in middle life is a risk factor for later dementia, prompt consideration of factors associated with lipid metabolism in the development of Alzheimer's dementia.

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PubMedDate not supplied

Elevated alpha 1-antichymotrypsin serum levels in a subset of nondemented first-degree relatives of Alzheimer's disease patients.

A portion of Alzheimer's disease (AD) patients have elevated serum levels of the acute phase reactant alpha 1-antichymotrypsin (A1ACT) compared to age-matched controls. We measured serum levels of A1ACT in AD patients, age-matched controls, Down's syndrome patients, and nondemented first-degree relatives of AD patients. Significantly elevated levels of A1ACT were found in both AD patients and first-degree-relatives. In AD patients, serum A1ACT concentrations decreased with increasing severity of cognitive impairment. These results may suggest that inflammatory phenomena may be an early component of AD pathophysiology.

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