Presence of the APOE epsilon4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine-Syracuse Study.

AIMS/HYPOTHESIS: The primary aim of this study was to determine whether the presence of one or more APOE epsilon4 alleles modifies the association between diabetes (defined by glucose > or =7 mmol/l or treatment) and cognitive function. METHODS: Diabetic status and APOE genotype interactions were assessed cross-sectionally for 826 community-dwelling, stroke-free, non-demented individuals (526 non-diabetic non-APOE epsilon4 carriers, 174 non-diabetic APOE epsilon4 carriers, 87 diabetic APOE epsilon4 non-carriers, 39 diabetic APOE epsilon4 carriers) ranging in age from 50 to 98 years. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the similarities subtest from the Wechsler Adult Intelligence Scale, and four composite scores derived from 17 additional neuropsychological tests. Multiple linear regression analyses were employed to relate diabetes and APOE genotype to cognitive performance and to examine the interaction between these two risk factors as they relate to cognitive performance. Multiple cardiovascular disease risk factors were statistically controlled. RESULTS: With adjustment for age, education, sex, race/ethnicity and APOE genotype, performance level was lower for the diabetic than for the non-diabetic group for the MMSE, the similarities subtest and each of the cognitive composites with the exception of the verbal memory composite. Interactions (p < 0.05) between diabetes and APOE genotype were found for all but the visual-spatial memory/organisation composite. The negative association between diabetes and cognitive performance was of a higher magnitude for individuals who carry one or more APOE epsilon4 alleles. Results were similar with additional adjustment for cardiovascular disease and associated risk factors. CONCLUSIONS/INTERPRETATION: The presence of one or more APOE epsilon4 alleles modifies the association between diabetes and cognitive function.

NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study.

OBJECTIVE: To determine if NIDDM and blood pressure are risk factors for poor cognitive performance and if history and duration of NIDDM and blood pressure interact such that the risk of poor performance is greater for subjects with both NIDDM and hypertension. RESEARCH DESIGN AND METHODS: We used a large prospective cohort sample with 187 NIDDM subjects and 1,624 nondiabetic subjects who were followed for 28-30 years. Cognitive function was assessed using eight tests of learning, memory, visual organization, verbal fluency attention, concept formation, and abstract reasoning. A composite score was also calculated. Odds ratios were used to estimate the relative risk of performing below the lower 25th percentile of z scores on these tests. RESULTS: NIDDM and blood pressure interacted such that diagnosis and duration of NIDDM were associated with greater risk of poor performance on tests of visual memory and on the composite score for hypertensive subjects. Duration of NIDDM was associated with increased risk for poor performance on tests of verbal memory and concept formation. Insulin-treated NIDDM subjects were at higher risk for poor cognitive performance than those NIDDM subjects treated with oral agents or diet. Blood pressure level was associated independently with a measure of verbal fluency. CONCLUSIONS: History and duration of NIDDM and high blood pressure are significant risk factors for poor cognitive performance. Hypertensive people with NIDDM are at greatest risk for poor performance on tests measuring visual organization and memory.

Clinical significance of cognitive performance by hypertensive patients.

Fifty-four subjects with uncomplicated essential hypertension and 54 normotensive subjects were compared with regard to a widely employed clinical index of cognitive dysfunction (the Average Impairment Rating) calculated from neuropsychological tests that discriminate between brain-damaged and neurologically normal persons. Hypertensive subjects exhibited lower mean scores on this index when education was ignored, but results were not the same for highly educated and less well educated groups. There were no differences between exceptionally well educated hypertensive and normotensive subjects, but in the less well educated group, hypertensive subjects performed more poorly than normotensive subjects. The percentages of hypertensive and normotensive subjects scoring in a cognitively impaired range on the Average Impairment Rating were low and did not differ for either education group. These data indicate the important role of subtle differences in education level with respect to positive or negative findings for studies comparing hypertensive and normotensive subjects and illustrate the important role of clinical neuropsychological indices of cognitive dysfunction when one wishes to make meaningful inferences regarding cerebral cortical function in hypertensive subjects.

A longitudinal study of blood pressure in relation to performance on the Wechsler Adult Intelligence Scale.

A growth curve analysis was used to examine estimated longitudinal decline (over 19 years) on the Wechsler Adult Intelligence Scale (WAIS; D. Wechsler, 1955) in relation to arterial hypertension and blood pressure (BP) for 55 men and 85 women (40 to 70 years old) who were free from overt major coexisting diseases. BP was associated with longitudinal decline for Visualization-Performance (VP) ability and Speed. Hypertension was a weaker predictor of VP and was unrelated to Speed. Age effects on VP were overestimated when averaged BP level, particularly systolic BP, was not controlled statistically. It was concluded that initial BP level and hypertension predict age-related longitudinal decline in specific major abilities assessed by the WAIS but that BP averaged over examinations is a stronger predictor.

Acquisition of word-processing skills by younger, middle-age, and older adults.

A total of 45 subjects in three age groups (younger, middle-age, older) were trained to word process on microcomputers using a commercial training program and an experimenter-designed test and evaluation protocol. Although all of the subjects mastered the essentials of word processing, the older group took significantly longer to complete the training and evaluation procedures and performed more poorly on a review examination that tested their knowledge of the word-processing commands and techniques. The results are discussed in relation to requirements for trainer assistance, motivational factors, and the need to design training protocols that meet the needs of older adults.

A 15-year longitudinal study of Halstead-Reitan neuropsychological test performance.

Using a two-stage growth curve analysis, change over time in performance on tests in the Halstead-Reitan Battery and Average Impairment Rating (AIR) was assessed for 53 individuals who varied in age and health status. In the first stage of the analysis, estimated slope and intercept values were calculated for each individual by regressing longitudinal data points on time. In the second stage, estimated slope and intercept values obtained in the first-stage analysis were regressed on age at entry into the study with statistical control for health status, education, occupation, and gender. Control for health status had an insignificant influence on magnitude of associations between age and test performance. Age-at-entry into the study was associated with statistically significant increasing change over time (poorer performance) for tests placing relatively heavy demands on speed of psychomotor performance and for AIR.

Effects of immobilization stress on open field behavior and plasma corticosterone levels of aging C57BL/6J mice.

Four age groups of C57BL/6J mice (2.2, 6.2, 12.0, and 23.3 months) were subjected to either immobilization or handling (control) procedures. Open field behavior was observed before and after experimental treatments and plasma corticosterone levels were assessed 11 days following the immobilization or handling procedures. Eleven days following immobilization elevated corticosterone levels were observed for all but the 12.0 month group of mice. No behavioral effects were observed for the experimental groups, although both locomotor activity and exploratory behavior declined with advancing age. The age-related decrease in activity was entirely accounted for by scores on the initial open field test. Exploratory behavior was observed to be a more complex function of both age and experience.

Effects of age on learning ability: contributions from the animal literature.

For both ethical and practical reasons, animal subjects are becoming increasingly important tools for life span developmental researchers. Selected studies from the animal literature which have important implications for the study of learning in a life span context are reviewed. Specific issues discussed include task difficulty, genotype effects on life span learning processes, perseveration, and early versus later experience. It was concluded that 1) the hypothesis that task difficulty has a greater effect on senescent animals relative to younger animals generally is supported by the current literature, 2) genotype is a highly relevant variable for life span developmental research, but little work has been dirrected toward how genotype affects behavior within specific environmental contexts, 3) perseveration is very likely an important factor in poorer performance among aged subjects, but it has not been adequately studied in relation to physiological correlates, earlier precursors, or genotype, 4) the issue of the importance of early versus later experience has not been resolved, but research in this area promises much information with regard to potential modifiers of a decline in learning ability with increasing age.

Emotionality, exploratory behavior, and locomotion in aging inbred strains of mice.

Two inbred strains of mice, C57BL/6J and DBA/2J, ranging in age from 2 to 38 months, were tested in an open field using the free exploration method. Scores were obtained for locomotor activity, exploratory behavior and emotionality. Strain differences were observed for all three variables. Beginning at late maturity (12 months), locomotor activity decreased with increasing age. Exploratory behavior was at a low level for DBA/2J mice at all ages. For C57BL/6J mice, exploratory behavior decreased significantly between 2 and 6 months and remained stable thereafter. Emotionality remained unchanged with advancing age for both strains of mice.

Sociocultural variability in infant temperament ratings.

The interaction between the temperament of children and their caretaking environment is thought to be an important factor in the etiology of childhood behavior deviance. Most recent research in infant temperament has used a maternal questionnaire. Scores from these questionnaires have been subject to low concurrent validity. Also, there have been indications that maternal characteristics such as anxiety level influence child temperament ratings. The present study examined mother characteristics, child behavior, and mother's temperament ratings when their babies were 4 months old. The social status, anxiety level, the mental health status of the mother were all related to temperament ratings on the Carey Infant Temperament Questionnaire. However, child behavior measured in the home and laboratory were sporadically related to temperament, and these relations were of small magnitude. Hierarchical multiple regression analysis demonstrated that mother effects were powerful than child effects. These results supported the notion that individual differences in mothers, rather than differences in infants, may be the major contributor to early ratings of temperament.

Some methodological problems in age comparisons of EEG sleep patterns for C57BL/6J mice.

Some methodological problems encountered in age comparisons of EEG patterns are discussed in the context of an analysis of open field activity scores before and after preparation for, and recording of EEG sleep patterns. Plasma corticosterone levels 11 days after surgery for EEG electrode implantation were also measured. Activity levels were modified more for three older than for a younger group of animals following surgery/recording sessions. Corticosterone levels were appreciably elevated for the oldest group of animals. The possibility was raised that procedures designed to allow recovery from post surgical shock and adaptation to electrode connections may result in disproportionate differences across age groups.

Blood pressure, hypertension, and age as risk factors for poor cognitive performance.

The relationships of three blood pressure variables (systolic and diastolic pressures and chronicity of hypertension) and age to cognitive performance on the Kaplan-Albert Neuropsychological Test Battery were explored in a sample of 1,695 stroke-free participants of the Framingham Heart Study. Multiple blood pressure measurements were obtained over four or five exams extending over 8-10 years. Neuropsychological testing was conducted 12-14 years after the final blood pressure measurement. Data were subject to multiple binary logistic regression analyses, and odds ratios were calculated for performance in the lower 50th and 25th percentiles for 10-mmHg increases in diastolic blood pressure, 20-mmHg increases in systolic blood pressure, proportion of exams (out of four or five) in which participants were diagnosed as hypertensive, and 10-year increases in age. Blood pressures and chronicity of hypertension were inversely associated with performance on visual and verbal memory tests of the Kaplan-Albert battery. Age was inversely associated with performance on all tests in the battery. Generally, the odds of performing poorly were higher for age than for the blood pressure variables. The epidemiological significance of these findings is discussed in terms of implications for public health and management of hypertension.

Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study.

Interactions of three indices of blood pressure (systolic blood pressure, diastolic blood pressure, and chronicity of hypertension) and age-cohort membership were examined for a sample of 1,695 stroke-free participants of the Framingham Heart Study, ages 55-88 years. Blood pressure level and chronicity of hypertension were assessed over five biennial examinations performed between 1956 and 1964, a time when few hypertensives were being treated, and were related to neuropsychological tests administered between 1976 and 1978. Multiple linear regression methods were used to examine Age x Blood Pressure (or Chronicity of Hypertension) interactions in alternative analyses involving three age groups (55-64 years, 65-74 years, and 75-88 years) and age as a continuously distributed variable (age in years). Interactions were either statistically nonsignificant or trivial with respect to magnitude of effect. This was true when interaction terms (Age x Blood Pressure Level or Age x Chronicity of Hypertension) were controlled for blood pressure, age, education, occupation, cigarette smoking, alcohol consumption, gender, and antihypertensive treatment. The Age x Blood Pressure model as it pertains to older adults was not supported, but independent associations (with all covariables controlled) between the indices of blood pressure and cognitive functioning were statistically significant.

Heart/body weight ratios for aging high and low blood pressure mice.

Heart weight and heart/body weight ratios were determined for stocks of mice bred from Schlager's high and low blood pressure mice. Results of an analysis in which three different age groups (means = 15, 17, and 28 months) were compared indicated a nonsignificant interaction between age and blood pressure for heart weight and between age and blood pressure for heart/body weight ratios. Heart weight and heart/body weight ratios were significantly higher for the high than for the low BP mice at all ages with one exception; heart weights did not differ between the two lines at mean age 28 months. It was concluded that high blood pressure mice do not exhibit cardiac hypertrophy in the strictest sense of a disproportionately greater increase in heart/body weight ratios across the life span than low blood pressure for this particular stock.

A longitudinal study of neuropsychological performance by hypertensives and normotensives: a third measurement point.

The neuropsychological test performance of hypertensive and normotensive subjects was compared at three times of measurement over a 10-year period. The tests used were among those that are most sensitive to brain impairment in the Halstead-Reitan battery. In addition to individual test measures, a widely used clinical index of battery-wide performance--the Average Impairment Rating (AIR)--was used. Hypertensives exhibited lower mean levels of performance on the AIR at all times of measurement. However, the Blood Pressure Group x Time of Measurement interactions were not statistically significant, indicating that hypertensives and normotensives did not exhibit a differential rate of change (decline or improvement) over time. Hypertensives also performed more poorly for a measure of learning set formation (categories test) and two tests of memory for forms experienced by touch only (tactile perception memory and localization tests). However, Blood Pressure x Time of Measurement interactions were not observed for these measures.

Alcohol consumption and cognitive performance in the Framingham Heart Study.

Recent studies have indicated that moderate alcohol intake may be beneficial to cognitive functioning in women, although not necessarily in men. Data from the Framingham Heart Study, a large, prospective study of cardiovascular disease in Framingham, Massachusetts, were used to examine the relation between alcohol consumption and cognitive ability. The major research question was whether a different alcohol-cognition relation would be found for male and female drinkers. Men (n = 733) and women (n = 1,053), aged 55-88 years, were queried as to their weekly intake of alcohol, and these data were used to construct groups of abstainers, very light, light, moderate, and heavy drinkers. Data from earlier reports of alcohol consumption were also examined. Participants were administered eight tests which reflect performance in the domains of verbal memory, learning, visual organization and memory, attention, abstract reasoning, and concept formation. Multivariate linear regression analyses were used with statistical adjustment for age, education, occupation, cardiovascular disease, and associated risk factors. Women who drank moderately (2-4 drinks/day) showed superior performance in many cognitive domains relative to abstainers. For men, superior performance was found within the range of 4-8 drinks/day, although fewer significant relations were observed. These results were confirmed by prospective analyses of 24-year drinking history.

Role of age, education, and gender on cognitive performance in the Framingham Heart Study: community-based norms.

Normative data are presented for a neuropsychological test battery (Kaplan-Albert) consisting of subtests from the original Wechsler Adult Intelligence and Memory Scales and the Benton and Hamsher Aphasia Examination. Analyses were based on archival data resulting from administration (1976-1978) of the battery to community residents participating in the Framingham Heart Study, a prospective, longitudinal study of cardiovascular risk factors. Using 3 age groups (55-64, 65-74, and 75-88 years) and 4 education levels (5-8, 9-11, 12, > 12 years), individuals were stratified by age, gender, and education. Multiple linear regression analysis was used to relate main effects (age, education, and gender) and interactions of these effects to 9 test scores and to 2 composite scores identified by factor analysis. The oldest participants who had the fewest years of formal education had the lowest performance levels, with lower levels of performance for men than women in this least educated elderly cohort.

Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.

OBJECTIVE: To determine the independent effects of obesity and hypertension on cognitive functioning. METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified by presence or absence of obesity and hypertension based on data collected over an 18-y surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, cigarette smoking, alcohol consumption, total cholesterol, and a diagnosis of type II diabetes. Body mass index status (nonobese or obese) and blood pressure status (normotensive or hypertensive) were then related to cognitive performance (learning, memory, executive functioning, and abstract reasoning) on tests administered 4-6 y later. RESULTS: Adverse effects of obesity and hypertension on cognitive performance were observed for men only. Obese and hypertensive men performed more poorly than men classified as either obese or hypertensive, and the best performance was observed in nonobese, normotensive men. CONCLUSIONS: The adverse effects of obesity and hypertension in men are independent and cumulative with respect to cognitive deficit.