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.

The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a casecontrol study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy controlgroup members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of ''diversity'' (total number of activities), ''intensity'' (hours per month), and ''percentage intensity'' (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20 -39) to middle adulthood (40 -60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.case-control study ͉ dementia ͉ epidemiology ͉ leisure ͉ recreation

To assess the occurrence and related features of motor vehicle crashes in patients with dementia of the Alzheimer type (DAT) we studied 30 patients who had been followed longitudinally and 20 healthy age-matched control subjects. Data were gathered from first-degree relatives who had lived with the subjects for the previous 5 years or more. Forty-seven percent of the DAT patients incurred at least one crash while they were driving, whereas only 10% of the control subjects had had a crash in the previous 5 years. The odds ratio for crashes in the DAT group was 7.9 (p less than 0.01). Moreover, in 77% of DAT patients, a deterioration in driving performance was noted, and 63% of the patients had stopped driving. However, only 42% of the DAT patients who stopped driving did so before a crash occurred. Mean illness duration was 4.0 (+/- 1.8) years, and the mean Mini-Mental Status Examination score was 19.9 (+/- 6.3) at the time of the first crash in the DAT group. The occurrence of crashes was not significantly correlated with dementia severity or with disease duration. These data suggest that the occurrence of driving crashes in patients with DAT is an important public health problem.

No abstract

Retrieval from semantic memory, measured by tasks requiring subjects to name items from a given category, was studied in mild Alzheimer-type dementia (Mild-ATD) subjects, moderate-to-severe Alzheimer-type dementia (MS-ATD) subjects, and normal controls. Semantic retrieval performance was shown to be highly sensitive to both the presence and the severity of ATD. Retrieval from both semantic categories and letter categories showed differences in the rate of production of correct responses between subject groups. These rate differences were not due to differences in accessibility of low-dominance semantic category members or low-frequency letter category members. An increase in errors as well as a decrease in correct responses contributed to the performance deficits of the ATD subjects. Furthermore, the pattern of errors changed from Mild- to MS-ATD. Qualitative as well as quantitative differences were also observed in the performance of Mild- versus MS-ATD groups on a third type of semantic retrieval task--the supermarket task. As performance of the ATD subjects declined on these semantic retrieval tasks, so did their performance on other tasks assessing primarily attention, language, and memory. The findings are discussed in terms of the progressive breakdown in both attentional and semantic memory functions which are associated with ATD.

To determine whether the age of the onset of Alzheimer's disease (AD) is related to the expression and rate of decline of this disorder, we examined the clinical and neuropsychological performance of 421 patients entered into the Consortium to Establish a Registry for Alzheimer's Disease and followed annually for up to 4 years. Statistical analyses were based on multivariable logistic regression analysis for dichotomous clinical measures and multivariable linear regression analysis for psychometric measures. All analyses examined the effect of age after controlling for gender, education, and stage of dementia. Clinical information obtained on entry into the study indicated that younger patients performed more poorly on measures of language and concentration, and older patients performed more poorly on measures of memory and orientation. On neuropsychological measures at entry, younger patients, performed more poorly on praxis and had significantly higher scores of confrontation naming. Younger age predicted a significantly faster rate of progression for all neuropsychological measures. These findings support the concept of age-related clinical subtypes of AD.

The parietal-frontal distribution of reductions of regional cerebral metabolic rates for glucose (rCMRglc) was studied in 32 patients with mild to severe dementia of the Alzheimer type (DAT), using positron emission tomography and fluorodeoxyglucose, and was related to patterns of neuropsychological impairment. In moderate and severe DAT patients, one frontal association region, the premotor cortex, demonstrated significant metabolic reductions equivalent to reductions in the parietal association cortex, and the ratio of parietal to premotor rCMRglc had significantly greater variance than in controls. In moderately demented patients, parietal-premotor and parietal-prefrontal metabolic ratios correlated significantly with neuropsychological impairments. Disproportionate parietal hypometabolism was associated with more impairment of verbal comprehension, calculations, visuospatial construction, and immediate visuospatial memory span. Disproportionate frontal hypometabolism was associated with more impaired verbal fluency and attention. Longitudinal follow-up of 20 of the patients showed that parietal/frontal metabolic ratios and their correlated neuropsychological patterns were stable over time, as dementia severity worsened. These results indicate that in moderate to severe DAT patients, metabolic reductions in the premotor cortex are as severe as the reductions in the parietal association cortex. Moreover, the parietal-premotor distribution of metabolic reductions is variable and related to variable patterns of cognitive impairment.

During primary PCI, physician experience significantly modifies the hospital volume-outcome relationship. Therefore, policymakers need to consider physician experience when developing strategies to improve access to primary PCI.