Staging methods for the assessment of dementia: Perspectives.

Most dementias in old age are characterized by a progressive course with interindividual variability in pattern and rate of progression. Developing a system for staging such dementia poses a challenge in capturing this variability in a system that will afford comparisons among individuals and predictions of future change. Several core questions underlie the development of such systems: (1) Is there a definable order in which abilities are lost? (2) Which skills and functions should be considered essential for the staging of dementia and what is their relative weight? (3) Can the different skills be captured within one staging system? (4) How is the whole range of function captured, and are the differences between stages clearly defined? (5) Which populations can be rated with each staging system? The determination of this last question is based on understanding which other medical conditions may interfere with the course of dementia and how prior characteristics, such as education, affect ratings on specific scales for the staging of dementia. Several systems for staging dementia in older adults are described. These include the Clinical Dementia Rating, the Global Deterioration Scale/Brief Cognitive Rating Scale/Functional Assessment Staging System, the Six Clinical Phases of Cognitive Decline, the Hierarchic Dementia Scale, and the Functional Capacity Scale. Some aspects of the utility of these systems are reviewed, and the issues for further research are discussed.

Prevalence of Alzheimer's disease in a retirement community.

In a white, predominantly middle class southern California retirement community, 817 adults aged 65-99 years were evaluated in 1980-1982 in a study designed to assess prevalence of early Alzheimer-type senile dementia. Based on 162 neurologically diagnosed cases, the age- and sex-adjusted prevalence of Alzheimer's disease in the target population was 15.3% (95% confidence interval = 13.0-17.5) among persons aged 65+ years and 35.8% among persons aged 80+ years. Age-adjusted correction for false negatives not detected by a screening procedure yields an estimated prevalence of 16.4% in persons aged 65+ years. Validity of the diagnostic approach was confirmed by a follow-up study. These rates far exceed past prevalence estimates for this disease. Since prevalence of mid- or later stages of Alzheimer's disease may have been underestimated, the high rates in this study may reflect a considerable community burden of early disease. Observed prevalence of Alzheimer-type senile dementia was higher among men than women after adjustment for age, 19.1% and 13.1%, respectively. The female predominance reported in many past clinical surveys may be peculiar to late disease and reflect care-seeking and care-utilization behaviors, rather than differences in incidence.

Use of the mental function index in older adults. Reliability, validity, and measurement of change over time.

The Mental Function Index is a weighted combination of scores on three brief tests. The Index was developed to aid in the discrimination of elderly persons with early cases of senile dementia from nondemented elderly individuals. In a previous report (Am J Epidemiol 1981;114:515-27), the authors described preliminary results with the Index in 195 elderly persons in a southern California retirement community. The present study seeks to assess whether similar results can be achieved in samples other than that from which the discriminant function defining the Index was derived. Seven separate studies were done on a total of 210 persons, comprising subjects recruited from a teaching hospital which serves a predominantly lower to lower-middle class population, referrals from the same physicians as in the earlier study, and (for the reliability sample) persons from the upper-middle class community which was the major referral source. It was found that scores on the brief measures correlate 0.86 with those on the three Halstead-Reitan subtests most sensitive to brain damage and to aging. The Index provides a graded measure of disease severity comparable to global neurologic assessment (r = -0.84) and level of social function (r = 0.76). Entry Index is a crude predictor of cognitive status in older adults after several years. Changes in the Index over time parallel those in independent measures of change. The results suggest that the Index will be useful for assessment of disease severity and of longitudinal change, as well as for diagnostic screening, in population studies of senile dementia.

Measurement of functional activities in older adults in the community.

Two measures of social function designed for community studies of normal aging and mild senile dementia were evaluated in 195 older adults who underwent neurological, cognitive, and affective assessment. An examining and a reviewing neurologist and a neurologically trained nurse independently rated each on a Scale of Functional Capacity. Interrater reliability was high (examining vs. reviewing neurologist, r = .97; examining neurologist vs. nurse, tau b = .802; p less than .001 for both comparisons). Estimates correlated well with an established measure of social function and with results of cognitive tests. Alternate informants evaluated participants on the Functional Activities Questionnaire and the Instrumental Activities of Daily Living Scale. The Functional Activities Questionnaire was superior to the Instrumental Activities of Daily scores. Used alone as a diagnostic tool, the Functional Activities Questionnaire was more sensitive than distinguishing between normal and demented individuals.

A survey diagnostic tool for senile dementia.

To validate a senile dementia survey diagnostic tool, 195 individuals aged 61-91 and referred by their physicians as normal or mildly demented were examined. The etiologic diagnosis used as criterion was the consensus of two experienced neurologists, assisted by clinical and laboratory data from referring physicians and by neuropsychologic evaluation of questionably affected persons. Agreement between the neurologists was high, as indicated by a weighted Kappa coefficient of 0.97 (95% confidence interval (Cl) (0.94, 1.00)). Agreement between the instrument and criterion diagnosis was also excellent (kappa w = 0.93; 95% Cl (0.88, 0.98)). Used alone as a screening diagnostic tool, the cognitive function portion of the instrument was much more sensitive (0.929) than previously used brief tests and was acceptably specific (0.800). Because normals complete this cognitive test in 15-20 minutes, it should be a major advance in population-based studies of senile dementia and normal aging.

Estrogen use and blood pressure in later life.

Use of oral estrogens did not alter the blood pressure (BP) or BP lability of women aged 52--87. The effect was similar in normotensives and women who were hypertensive before starting estrogen. Compared with nonusers of estrogen, users had lower systolic pressures, but did not differ in diastolic blood pressure, lability, frequency of doctor visits or BP determination, obesity, smoking or use of alcohol or psychotropic medication. The data neither confirm a previously reported association between estrogen use and hypertension nor do they suggest pre-selection of users for hypertension or labile BP.

Coronary risk and estrogen use in postmenopausal women.

Of some 15,500 women resident in a retirement community during an 11 year interval, 220 suffered a cardiologically ascertained first myocardial infarction. A case-control study demonstrated no association between estrogen use and myocardial infarction. The observed lack of association may be explained by an already high coronary risk in this age group, by the low daily estrogen dose, and by the short duration of estrogen use. The well-known association between hypertension and myocardial infarction was confirmed.

Estrogen use in postmenopausal women.

Fifteen per cent of postmenopausal women living in a retirement community used oral estrogens. Both use and new-use continued in the seventh, eighth and ninth decades of life, although use and age-specific use-prevalence declined after age 70. Mean duration of most recent continuous use was 105 months. Vaginal estrogenic preparations were used infrequently, briefly, and usually by women who also used oral estrogens in the same year. The most commonly used oral estrogenic preparation was conjugated equine estrogens (Premarin).

Estrogens and endometrial cancer in a retirement community.

All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer.

Estrogen use and stroke risk in postmenopausal women.

Among postmenopausal women (58-98 years of age) in a retirement community use of oral estrogens was not significantly associated with overall risk of stroke. Estrogen use was significantly associated with blood-pressure status. An observed association between estrogen use and nonembolic cerebral infarction in women aged 70-79 may be secondary to an interaction between hypertension and estrogen usage.

PIP: A retrospective case-control study of the association between the use of estrogens and the risk of stroke in postmenopausal women, aged 58-9 8 years, is presented. The data did not reveal a marked primary effect of estrogen use on the overall risk of stroke. There was, however, a significant association between estrogen use and the development of hypertension (p less than .005). Subanalysis revealed a possible adverse effect of estrogens on the risk of nonembolic infarction in women aged 70-79 years. Further analysis of these associations is recommended.

Time course of the effect of reserpine administration on tyrosine hydroxylase activity in adrenal glands and vasa deferentia.

During the first several hours after administration of reserpine, tyrosine hydroxylase activity in rat adrenal slices and in isolated intact vasa deferentia of mice and rats is profoundly reduced, although no effect on enzyme activity in isolated fortified homogenates of these tissues is demonstrable. This effect, observed only in intact preparations, is competitively antagonized by addition to the medium of the synthetic pterin cofactor, 6,7-dimethyltetrahydropterin (DMPH4). Kinetic analysis of the effect of acute reserpine treatment on tyrosine hydroxylase activity in these isolated, intact tissues indicates that the Km for the pterin cofactor is increased but the Vmax is not altered. The results indicate that reserpine produces its inhibition of tyrosine hydroxylase by preventing catecholamine storage and causing elevated levels of free intraneuronal norepinephrine. The catecholamine inhibits the enzyme in a manner which is competitive with the pterin cofactor. After more chronic reserpine treatment, when catecholamine stores are severly depleted, this inhibition of tyrosine hydroxylase activity in intact tissues is no longer apparent. After 3 days of treatment, increased levels of tyrosine hydroxylase are demonstrable in the adrenal glands of rats but not in the vass deferentia of either mice or rats. The increased enzyme levels in the adrenal gland are presumably due to increased enzyme formation.