Correlates of the "don't know" response to questions about snoring.

Many persons say that they "don't know" whether they snore. The purpose of this study was to investigate the prevalence and correlates of such responses in an elderly population. Subjects were 1715 members (1,155 men, 560 women) of a previously defined cohort (Western Group Collaborative Study) followed prospectively since 1960-1961 with a current mean age of 75.9 (SD = 4.3) for the men and 71.4 (SD = 5.3) for the women. We collected survey questionnaires and reviewed medical records. Results indicated that risk factors for the "don't know" response in this population were similar to those for frequent snoring and included: male sex, higher Body Mass Index, smoking, and use of sinus medication. Between 28 and 44% of the cohort answered questions about snoring with a "don't know" response. These data are compatible with the interpretation that subjects may disavow knowledge of their own snoring and suggest that future studies consider the "don't know" response to questions about snoring as a response of potential interest.

Neuropsychological performance of Hispanic and non-Hispanic older adults: an epidemiologic survey.

Performance on a brief battery of neuropsychological tests was compared for 797 Hispanic and non-Hispanic white older adults (65-97 years) participating in a community-based epidemiological survey of Bernalillo County, New Mexico. Tests included measures of memory (Fuld Object Memory Evaluation), attention (Digit Span), verbal fluency (category naming), visuoconstruction (clock drawing), and psychomotor speed and cognitive flexibility (Color Trails). Statistically significant ethnic group differences were observed on all tests in analyses that also considered effects of age, education, gender, depressive symptoms, and a global measure of medical illness. Effect sizes were small for all measures except Digit Span and Color Trails. In dementia screening or other clinical cognitive assessment, separate ethnic group norms may be useful in interpreting results for these measures. Preliminary normative tables are provided for Hispanic older adults at two levels of age (65-74 years and 75-97 years) and four levels of education (0-6 years, 7-9 years, 10-12 years, and > 12 years).

Relationship between 24-Hour Ambulatory Blood Pressure and Cognitive Function in Healthy Elderly People.

This study explored the relationship between cognitive function and blood pressure (BP) in 84 women and 64 men, aged 55-79. Assessments were made of casual BP, 24-hour ambulatory BP, and cognitive function. Participants had no evidence of any health disorders, were taking no medication, and were primarily normotensive. By means of principal components analysis, the number of variables was reduced to three BP components of Level, Wake Variability, and Sleep Variability and four cognitive components of Psychomotor Speed/Cognitive Flexibility, Attention, Verbal Memory, and Short-term/Working Memory. Elevated ambulatory BP (level and variability) was associated with difficulties in Attention and Short-term/Working Memory. The fact that increased risk of poorer cognitive function may be related to BP in an elderly population with relatively low BP means that even moderate elevations in BP may be cause for concern.

Mnemonics usage and cognitive decline in age-associated memory impairment.

To determine predictors of cognitive deterioration, the authors performed baseline and 1- to 5-year follow-up (mean +/- SD = 2.5 +/- 1.2 years) neuropsychological assessments on 36 persons (mean age +/- SD = 62.1 +/- 8.0; range = 50 to 81 years) with age-associated memory impairment. Subjects were recruited from a larger group of volunteers, had minimal medical comorbidity, and 25 of them had a family history of Alzheimer's disease. Baseline age and a subjective memory measure indicating reported frequency of mnemonics usage were significant decline predictors. Subjects reporting more frequent mnemonics use at baseline were more likely to show objective cognitive decline at follow-up. Baseline full-scale IQ, educational level, and family history of Alzheimer's disease failed to predict decline. These findings suggest that although age is the strongest decline predictor in some people with age-associated memory impairment, self-perception of memory function may also predict subsequent cognitive loss.

Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment.

Associations between nutritional status and cognitive performance were examined in 137 elderly (aged 66-90 y) community residents. Participants were well-educated, adequately nourished, and free of significant cognitive impairment. Performance on cognitive tests in 1986 was related to both past (1980) and concurrent (1986) nutritional status. Several significant associations (P < 0.05) were observed between cognition and concurrent vitamin status, including better abstraction performance with higher biochemical status and dietary intake of thiamine, riboflavin, niacin, and folate (rs = 0.19-0.29) and better visuospatial performance with higher plasma ascorbate (r = 0.22). Concurrent dietary protein in 1986 correlated significantly (rs = 0.25-0.26) with memory scores, and serum albumin or transferrin with memory, visuospatial, or abstraction scores (rs = 0.18-0.22). Higher past intake of vitamins E, A, B-6, and B-12 was related to better performance on visuospatial recall and/or abstraction tests (rs = 0.19-0.28). Use of self-selected vitamin supplements was associated with better performance on a difficult visuospatial test and an abstraction test. Although associations were relatively weak in this well-nourished and cognitively intact sample, the pattern of outcomes suggests some direction for further research on cognition-nutrition associations in aging.

Mood state and cerebral metabolism in persons with age-associated memory impairment.

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4 +/- 9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.

Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging.

New treatments for Alzheimer's disease (AD) are more likely to slow or halt disease progression rather than to reverse existing neuronal damage. Identifying persons with mild cognitive complaints who are at risk for AD will allow investigators to apply anti-dementia treatments before extensive brain damage develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4) as a major risk factor for AD offers promise of assisting in early detection and prediction of Alzheimer's disease, particularly when genetic assessments are combined with other biomarkers such as neuroimaging. Studies of relatives at risk for familial AD using neuroimaging (positron emission tomography [PET]) and genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4 have lower parietal metabolism than those without APOE epsilon 4. Additional techniques that might increase sensitivity and specificity include longitudinal assessment of clinical and brain functional change, pharmacological challenges of short-acting anticholinergic agents, and memory activation paradigms during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental anti-dementia treatment trials.

Predictors of cognitive change in middle-aged and older adults with memory loss.

OBJECTIVE: Previous longitudinal studies of age-related memory loss have focused on objective neuropsychological measures that predict subsequent cognitive change, yet brain metabolic function, self-perception of memory loss, and other measures may also be sensitive indicators of cognitive change. To determine such baseline predictors of change, the authors made longitudinal assessments of middle-aged and older adults with memory loss. METHOD: Forty-two persons (mean age = 60 years, range = 43-81) with memory complaints received comprehensive baseline assessments, including subjective neuropsychological measures, objective measures of visual-spatial memory (the Benton Visual Retention Test) and verbal memory (the Buschke-Fuld Selective Reminding Test), and positron emission tomography scans to determine neocortical glucose metabolism. At an average follow-up of 3 years, the objective neuropsychological measures were again used to quantify the degree of cognitive change. RESULTS: Multiple regression analyses indicated that parietal asymmetry, sex of the subject, and baseline visual-spatial memory score were significant predictors of change in visual-spatial memory; level of education and baseline verbal memory score predicted change in verbal memory. Other neocortical asymmetry scores, age, family history of Alzheimer's disease, cerebral atrophy, and self-ratings of use of mnemonics were not significant predictors of change. CONCLUSIONS: Measures of cerebral metabolism, objective memory performance, sex, and education may predict subsequent cognitive change in middle-aged and older persons with memory loss. Also, the parietal asymmetry found in persons with questionable dementia that progresses to probable Alzheimer's disease may be present very early in the course of age-related cognitive decline.

Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.

OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.

Cognition and depression in a cohort of aging men: results from the Western Collaborative Group Study.

Relationships between cognitive performance and self-ratings of depression on the Center for Epidemiologic Studies Depression scale (CES-D; L.S. Radloff, 1977) were examined for 1,217 older men. After controlling for demographic variables and both objective and subjective measures of health, significant associations were observed between several CES-D variables and measures of cognitive mental status, memory, and psychomotor speed. The Well-Being factor of the CES-D was the most robust predictor of cognitive scores. Therefore, for older adults with generally favorable health and socioeconomic resources, there may be a link between positive affect and maintenance of cognitive effectiveness.

Cognitive changes in young-old adults: effect of family history of dementia.

Cognitive performance of 40 first-degree relatives of patients with probable Alzheimer disease was compared to that of 24 matched controls without a family history of dementia. Across a test-retest interval ranging from 1 to 6 years, relatives more often showed evidence of cognitive decline, and in multivariate analyses of memory and intelligence measures, relatives of patients with early-onset dementia (< 67 years) showed greater decline than controls or relatives of patients with late-onset dementia. All changes observed to date are in the subclinical range, and further follow-up will be needed to determine the reliability of change trajectories. However, the findings suggest that family history of dementia may be worthy of monitoring in research on normal cognitive aging.

Self-reports of memory problems in relatives of patients with probable Alzheimer's disease.

This study examined the relationship between subjective memory complaints and performance on tests of memory by relatives of patients with probable Alzheimer's disease (AD) and by older adults without a family history of dementia. Relatives of AD patients did not differ significantly from controls either in level of complaint or in performance on neuropsychological tests. However, among relatives of patients with early-onset AD, significant correlations were found between performance on memory tests and self-rated changes in everyday memory. These findings raise the possibility that relatives who have entered the age range in which their parents or siblings developed dementia symptoms are monitoring their memory performance more diligently than relatives of patients whose illness began at much later ages or persons who have no close relatives with AD.

Commingling analysis of memory performance in elderly men.

Smalley et al. [(1992) Genet Epidemiol 9:333-345] found evidence of a mixture of two distributions in memory performance among offspring of patients with dementia of the Alzheimer type (DAT), suggesting that these groups reflect genotypic subgroups of carriers and non-carriers of a putative DAT gene. One prediction of this hypothesis is that, in the general population, two distributions of memory performance are present, with a smaller proportion of subjects in the low-scoring cluster than that found among the offspring sample, but similar to the prevalence of DAT in the elderly community-at-large. Memory performance was investigated in a large sample of normal elderly males (N = 1,149; mean age = 71.4 +/- 4.7 years) to test this hypothesis. Commingling analyses of performance on the Benton visual retention test demonstrated significant negative skewness in the distribution of memory performance, requiring a transformation to fit a single normal distribution. In the absence of a transformation, two distributions fit better than one, with 6% of subjects falling into a "low"-scoring cluster. These findings are consistent with the hypothesis that memory performance may represent a premorbid or morbid difference in those who go on to develop, or currently have, DAT, possibly allowing identification of at-risk carriers of a putative single major gene for DAT.

Age-associated memory loss: initial neuropsychological and cerebral metabolic findings of a longitudinal study.

To determine the relationships between clinical and brain function in persons with a familial risk for Alzheimer's disease, the authors assessed subjective and objective cognitive abilities, mood state, and cerebral glucose metabolism (using positron emission tomography) in 43 persons with age-associated memory impairment, with and without first-degree relatives with a clinical diagnosis of Alzheimer's disease. Subjective complaints of memory loss, mood state ratings, and objective memory measures were similar in persons with a family history of Alzheimer's disease (n = 29) compared to those without such a history (n = 14). Metabolic ratios in the frontal regions correlated with a decrease in a specific type of subjective memory complaint (mnemonics usage; p < .001) and some mood state ratings. These results indicate that parietal and temporal hypometabolism is not evident in persons with mild age-related memory complaints, even when such subjects have a familial risk for Alzheimer's disease. Moreover, self-reports of mnemonics usage may be sensitive indicators of decreased frontal lobe function. Longitudinal study will determine whether such clinical and metabolic measures will predict eventual disease progression.

Clinical, neuroimaging, and environmental risk differences in monozygotic female twins appearing discordant for dementia of the Alzheimer type.

OBJECTIVE: The study of monozygotic twins can elucidate possible environmental causes for a disease in genetically identical subjects. To this end, we studied a pair of monozygotic female twins appearing discordant for dementia of the Alzheimer type (DAT). DESIGN: Clinical and neuroimaging findings were compared in terms of potential environmental risk factors. SETTING: University referral center. PARTICIPANTS: An 81-year-old female monozygotic twin pair. OUTCOME MEASURES: Clinical assessments, standardized rating scales, and brain imaging studies, including magnetic resonance imaging, positron emission tomography, and electroencephalography, were performed. Neuropsychological tests were performed initially and after 1 year. RESULTS: Although DAT was confirmed clinically in only one twin, neuropsychological and brain imaging studies suggested that the unaffected twin may be developing the prodrome of DAT. The twins' varied life histories suggest that environmental risk factors may contribute to apparent discordance for DAT and possible delay in disease onset for the currently nondemented twin. CONCLUSIONS: These results suggest that both genetic and nongenetic factors influence disease onset and expression. Moreover, review of previous reports of monozygotic twin pairs concordant or discordant for Alzheimer's disease, with adequate family history data, suggest a pattern indicating interactions among age at dementia onset, sex, and familiarity. Such patterns point to hypotheses regarding neurobiologically meaningful Alzheimer's disease subgroups.

Cognitive performance in relatives of patients with probable Alzheimer disease: an age at onset effect?

Cognitive performance of 32 siblings and children of patients with probable Alzheimer disease was assessed longitudinally over an interval averaging 4 years. Mean scores were within normal limits for age on all measures at both test times. However, relatives of patients with early-onset dementia (less than or equal to 67 years) were more likely to show a decline in performance from the first to second testing than relatives of patients with late-onset dementia. Additional follow-up will be needed to determine the reliability of performance trajectories and to assess whether mild cognitive changes are related to future dementia. However, findings suggest that it may be important to consider family history of dementia in studies of normal cognitive aging.

Retrospective accounts of dementia symptoms: are they reliable?

Relatives of patients with dementia completed questionnaires about caregiver stress and patients' functional and psychiatric problems during an initial evaluation, at follow-up 4 to 17 months later, and retrospectively (i.e., based on recall of symptoms and behaviors at the initial assessment). Retrospective accounts correlated well with initial reports, particularly with larger scales including a wider range of alternative responses, but psychiatric symptoms were underreported in the retrospective accounts. Spouses tended to report lower levels of psychiatric symptoms than did younger relatives.

Recombinant human erythropoietin treatment may improve quality of life and cognitive function in chronic hemodialysis patients.

Medical, psychological, and social adaptation (quality of life) as well as cognitive function were studied in 15 chronic stable hemodialysis patients before the onset of treatment with recombinant human erythropoietin (r-HuEPO), 1 month after stabilization of normal hematocrit levels, and 10 to 15 months after treatment onset. After r-HuEPO treatment, subjects had significantly higher hematocrits, markedly improved energy levels, and marginally improved global health. r-HuEPO treatment was also associated with progressively decreased levels of subject mood disturbance and dialysis-related stresses. Subjects had no increased participation in paid employment and only minimally increased participation in social and leisure activities at posttreatment data points. There was no significant improvement in cognitive function after treatment. r-HuEPO treatment appears to be associated with higher energy levels, significant psychological benefits, and minimal improvements in social adaptation. The effects on cognitive function merit further study.

Patterns of performance on the Fuld Object Memory Evaluation in elderly inpatients with depression or dementia.

The Fuld Object Memory Evaluation (Fuld, 1981) was administered to 80 elderly adults (aged 60 to 90 years) who were hospitalized for evaluation and treatment of primary degenerative dementia (PDD), other organic disorders (e.g., Parkinson's disease or multi-infarct dementia), or major depression. Although mean performance in each of the diagnostic groups was below normative levels reported by Fuld (1981), PDD patients performed significantly more poorly than those with depression or other organic disorders. Analysis of subscore patterns failed to support the hypothesis of a selective memory deficit in depression, and substantial overlap in scores was observed between the depressed group and patients with organic disorders other than PDD. Object Memory Evaluation performance was influenced by global mental status and secondary psychiatric diagnoses, but not by education, age, or physical health.

Methodological concerns: longitudinal studies of dementia.

Common methodological problems in longitudinal research on dementia are discussed, applying terms and constructs from the literature on normal aging. Critique of prevailing methods suggests that longitudinal studies of dementia could be improved by more extensive pilot examination of dependent measures and by more stringent control of instrumentation bias. The impact of attrition also needs to be more thoroughly evaluated before generalizations are stated about rates and patterns of decline in dementing illness.