Association between vestibular function and rotational spatial orientation perception in older adults.

BACKGROUND: Spatial orientation is a complex process involving vestibular sensory input and possibly cognitive ability. Previous research demonstrated that rotational spatial orientation was worse for individuals with profound bilateral vestibular dysfunction. OBJECTIVE: Determine whether rotational and linear vestibular function were independently associated with large amplitude rotational spatial orientation perception in healthy aging. METHODS: Tests of rotational spatial orientation accuracy and vestibular function [vestibulo-ocular reflex (VOR), ocular and cervical vestibular evoked myogenic potentials (VEMP)] were administered to 272 healthy community-dwelling adults participating in the Baltimore Longitudinal Study of Aging. Using a mixed model multiple linear regression we regressed spatial orientation errors on lateral semicircular canal function, utricular function (ocular VEMP), and saccular function (cervical VEMP) in a single model controlling for rotation size, age, and sex. RESULTS: After adjusting for age, and sex, individuals with bilaterally low VOR gain (ß= 20.9, p = 0.014) and those with bilaterally absent utricular function (ß= 9.32, p = 0.017) made significantly larger spatial orientation errors relative to individuals with normal vestibular function. CONCLUSIONS: The current results demonstrate for the first time that either bilateral lateral semicircular canal dysfunction or bilateral utricular dysfunction are associated with worse rotational spatial orientation. We also demonstrated in a healthy aging cohort that increased age also contributes to spatial orientation ability.

A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging.

Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross-sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age-related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixed-effects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.

A prospective study of focal brain atrophy, mobility and fitness.

BACKGROUND: The parallel decline of mobility and cognition with ageing is explained in part by shared brain structural changes that are related to fitness. However, the temporal sequence between fitness, brain structural changes and mobility loss has not been fully evaluated. METHODS: Participants were from the Baltimore Longitudinal Study of Aging, aged 60 or older, initially free of cognitive and mobility impairments, with repeated measures of fitness (400-m time), mobility (6-m gait speed) and neuroimaging markers over 4 years (n = 332). Neuroimaging markers included volumes of total brain, ventricles, frontal, parietal, temporal and subcortical motor areas, and corpus callosum. Autoregressive models were used to examine the temporal sequence of each brain volume with mobility and fitness, adjusted for age, sex, race, body mass index, height, education, intracranial volume and APOE ɛ4 status. RESULTS: After adjustment, greater volumes of total brain and selected frontal, parietal and temporal areas, and corpus callosum were unidirectionally associated with future faster gait speed over and beyond cross-sectional and autoregressive associations. There were trends towards faster gait speed being associated with future greater hippocampus and precuneus. Higher fitness was unidirectionally associated with future greater parahippocampal gyrus and not with volumes in other areas. Smaller ventricle predicted future higher fitness. CONCLUSION: Specific regional brain volumes predict future mobility impairment. Impaired mobility is a risk factor for future atrophy of hippocampus and precuneus. Maintaining fitness preserves parahippocampal gyrus volume. Findings provide new insight into the complex and bidirectional relationship between the parallel decline of mobility and cognition often observed in older persons.

Contributions to lateral balance control in ambulatory older adults.

BACKGROUND: In older adults, impaired control of standing balance in the lateral direction is associated with the increased risk of falling. Assessing the factors that contribute to impaired standing balance control may identify areas to address to reduce falls risk. AIM: To investigate the contributions of physiological factors to standing lateral balance control. METHODS: Two hundred twenty-two participants from the Pittsburgh site of the Health, Aging and Body Composition Study had lateral balance control assessed using a clinical sensory integration balance test (standing on level and foam surface with eyes open and closed) and a lateral center of pressure tracking test using visual feedback. The center of pressure was recorded from a force platform. Multiple linear regression models examined contributors of lateral control of balance performance, including concurrently measured tests of lower extremity sensation, knee extensor strength, executive function, and clinical balance tests. Models were adjusted for age, body mass index, and sex. RESULTS: Larger lateral sway during the sensory integration test performed on foam was associated with longer repeated chair stands time. During the lateral center of pressure tracking task, the error in tracking increased at higher frequencies; greater error was associated with worse executive function. The relationship between sway performance and physical and cognitive function differed between women and men. DISCUSSION: Contributors to control of lateral balance were task-dependent. Lateral standing performance on an unstable surface may be more dependent upon general lower extremity strength, whereas visual tracking performance may be more dependent upon cognitive factors. CONCLUSIONS: Lateral balance control in ambulatory older adults is associated with deficits in strength and executive function.

Vitamin B12 and Homocysteine Associations with Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging.

OBJECTIVES: This study aimed to assess the independent associations of serum levels of vitamin B12 and plasma concentrations of homocysteine with gait speed decline. DESIGN, SETTING, PARTICIPANTS: This study utilized longitudinal analysis of participants 50 years or older from The Baltimore Longitudinal Study of Aging, N=774. MEASUREMENTS: Gait speed (m/s) was assessed using the 6-meter usual pace test. Vitamin B12 and homocysteine concentrations were collected using standard clinical protocols. Linear mixed effects regression was stratified by baseline age category (50-69, 70-79, and ≥80 years old). RESULTS: Mean follow-up time for the total study sample was 5.4 ± 2.0 years. No association between vitamin B12 and gait speed decline over the follow-up time for any age group was found. Elevated homocysteine concentrations were associated with decline in gait speed after adjustment for covariates (50-69: ß= -0.005, p=.057; 70-79: ß= -0.013, p<.001, ≥80: ß= -0.007, p=.054). CONCLUSION: Homocysteine and vitamin B12 are inversely related, yet only homocysteine was associated with gait speed decline in this population of healthy older adults. Given these results, future research should be directed towards investigating the relationship in populations with greater variation in vitamin B12 concentrations and other mechanisms influencing homocysteine concentrations.

Muscle Quality, Strength, and Lower Extremity Physical Performance in the Baltimore Longitudinal Study of Aging.

BACKGROUND: Muscle quality is defined as the force generated by each volumetric unit of muscle tissue. No consensus exists on an optimal measure of muscle quality, impeding comparison across studies and implementation in clinical settings. It is unknown whether muscle quality measures that rely on complex and expensive tests, such as isokinetic dynamometry and computerized tomography correlate with lower extremity performance (LEP) any better than measures derived from simpler and less expensive tests, such as grip strength (Grip) and appendicular lean mass (ALM) assessed by DXA. Additionally, whether muscle quality is more strongly associated with LEP than strength has not been fully tested. OBJECTIVES: This study compares the concurrent validity of alternative measures of muscle quality and characterizes their relationship with LEP. We also whether muscle quality correlates more strongly with LEP than strength alone. DESIGN: Cross-sectional analysis. SETTING: Community. PARTICIPANTS: 365 men and 345 women 65 years of age and older in the Baltimore Longitudinal Study of Aging. MEASURES: Thigh cross-sectional area (TCSA), isokinetic and isometric knee extension strength (ID), BMI adjusted ALM (ALMBMI) from DXA, and Grip. Concurrent validity was assessed as the percent variance of different measures of LEP explained by each muscle quality measure. In addition, we compared LEP relationships between each measure of strength and its correspondent value of muscle quality. Confidence intervals for differences in percent variance were calculated by bootstrapping. RESULTS: Grip/ALMBMI explained as much variance as ID/TCSA across all LEP measures in women and most in men. Across all LEP measures, strength explained as much variance of LEP as muscle quality. CONCLUSIONS: Grip/ALMBMI and ID/TCSA measures had similar correlations with LEP. Muscle quality did not outperform strength. Although evaluating muscle quality may be useful to assess age-related mechanisms of change in muscle strength, measures of strength alone may suffice to understand the relationship between muscle and LEP.

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial.

Aging in men is associated with loss of bone mass, impaired physical function and altered body composition. The objective of this proof-of-concept randomized, double-blind, placebo-controlled, parallel-group, single-center trial was to determine the relative effects of testosterone (T) and estradiol (E(2)) on bone mineral density, body composition, and physical performance in older men. The primary outcome was lumbar spine bone mineral density (BMD), and secondary outcomes were body composition, muscle strength, gait speed, and sex hormone concentrations. Forty three men (age range, 65-82 years; mean age 71 years) with low total T levels <350 ng/dL were randomized to one of three groups: 5 g transdermal testosterone gel (TT) (N = 16), anastrozole (AI) 1 mg (N = 14) or placebo daily (N = 13) for 12 months. Outcomes were assessed at baseline, 3, 6, and 12 months. Both TT and AI increased serum TT levels (>500 ng/dL, p < 0.05) compared to baseline; T values remained stable throughout the duration of the trial. At 12 months, TT improved the primary outcome of lumbar spine BMD (p < 0.01).Both interventions improved knee strength at 12 months compared to baseline (p < 0.05) while lean body mass significantly increased only in the AI group at 6 and 12 months (1.49 ± 0.38 kg, p < 0.01; 1.24 ± 0.39 kg, p < 0.05, respectively) compared to baseline. Interestingly, TT improved fast gait speed at 3 and 12 months (p < 0.01, p < 0.05, respectively). In summary, this proof-of-concept study confirms that aromatization of T is required for maintaining BMD in older men with low-T levels. The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed, an observation that needs to be verified in future studies.

Apical periodontitis and incident cardiovascular events in the Baltimore Longitudinal Study of Ageing.

AIM: To evaluate whether the presence of apical periodontitis (AP), root canal treatment (RCT) and endodontic burden (EB) - as the sum of AP and RCT sites - were associated with long-term risk of incident cardiovascular events (CVE), including cardiovascular-related mortality, using data on participants in the Baltimore Longitudinal Study of Ageing (BLSA). METHODOLOGY: This retrospective cohort included 278 dentate participants in the BLSA with complete medical and dental examinations. Periodontal disease (PD) and missing teeth were recorded. The total number of AP and RCT sites was determined from panoramic radiographs. EB was calculated as the sum of AP and RCT sites. Oral inflammatory burden (OIB) was calculated combining PD and EB. The main outcome was incident CVE including angina, myocardial infarction and cardiovascular-related death. Participants were monitored for up to 44 years (mean = 17.4± 11.1 years) following dental examination. Relative risks (RRs) were calculated through Poisson regression models, estimating the relationship between AP, RCT, EB, PD, OIB and incident CVE. RESULTS: Mean age at baseline was 55.0 ±16.8 years and 51.4% were men. Sixty-two participants (22.3%) developed CVE. Bivariate analysis showed that PD, EB, number of teeth and OIB were associated with incident CVE. Multivariate models, adjusted for socio-demographic and medical variables, showed that age ≥60 years (RR = 3.07, 95% CI =1.68-5.62), hypertension (RR = 2.0, 95% CI = 1.16-3.46) and EB ≥3 (RR = 1.77, 95% CI = 1.04-3.02) were independently associated with incident CVE. The association between OIB and incident CVE was reduced to nonsignificance after adjustments (RR = 1.97, 95% CI = 0.83-4.70). CONCLUSIONS: EB in midlife was an independent predictor of CVE amongst community-dwelling participants in the BLSA. Prospective studies are required to evaluate cardiovascular risk reduction with the treatment of AP.

Arterialized venous bicarbonate is associated with lower bone mineral density and an increased rate of bone loss in older men and women.

CONTEXT: Higher dietary net acid loads have been associated with increased bone resorption, reduced bone mineral density (BMD), and increased fracture risk. OBJECTIVE: The objective was to compare bicarbonate (HCO3) measured in arterialized venous blood samples to skeletal outcomes. DESIGN: Arterialized venous samples collected from participants in the Health, Aging and Body Composition (Health ABC) Study were compared to BMD and rate of bone loss. SETTING: The setting was a community-based observational cohort. PARTICIPANTS: A total of 2287 men and women age 74 ± 3 years participated. INTERVENTION: Arterialized venous blood was obtained at the year 3 study visit and analyzed for pH and pCO2. HCO3 was determined using the Henderson-Hasselbalch equation. MAIN OUTCOME MEASURE: BMD was measured at the hip by dual-energy x-ray absorptiometry at the year 1 (baseline) and year 3 study visits. RESULTS: Plasma HCO3 was positively associated with BMD at both year 1 (P = .001) and year 3 (P = .001) in models adjusted for age, race, sex, clinic site, smoking, weight, and estimated glomerular filtration rate. Plasma HCO3 was inversely associated with rate of bone loss at the total hip over the 2.1 ± 0.3 (mean ± SD) years between the two bone density measurements (P < .001). Across quartiles of plasma HCO3, the rate of change in BMD over the 2.1 years ranged from a loss of 0.72%/y in the lowest quartile to a gain of 0.15%/y in the highest quartile of HCO3. CONCLUSIONS: Arterialized plasma HCO3 was associated positively with cross-sectional BMD and inversely with the rate of bone loss, implying that systemic acid-base status is an important determinant of skeletal health during aging. Ongoing bone loss was linearly related to arterialized HCO3, even after adjustment for age and renal function. Further research in this area may have major public health implications because reducing dietary net acid load is possible through dietary intervention or through supplementation with alkaline potassium compounds.

Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging.

UNLABELLED: Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness. INTRODUCTION: Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. METHODS: We performed cross-sectional analyses of older (age >55 years) men (n = 472) and women (n = 473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models. RESULTS: In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, ß -0.076 and -0.073, respectively; both p < 0.05) and hip bending strength (Z, ß -0.097 and -0.09, respectively; both p < 0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, ß -0.31 and -0.29, respectively; both p < 0.05). There was no significant association between glycemic status and hip geometry in men. CONCLUSIONS: In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance.

Diet quality and social support: factors associated with serum carotenoid concentrations among older disabled women (the Women's Health and Aging Study).

PURPOSE: This study investigated the relationship between social support (including instrumental support, emotional support, social interaction, social space, and family networks) and diet quality, as indicated by serum carotenoid levels. DESIGN AND METHODS: The sample consisted of participants in the Women's Health and Aging Study with longitudinal carotenoid data (n=325). We performed regression analyses using baseline indicators of social support and changes in social support to determine whether baseline levels and/or change in levels of social support predict changes in serum carotenoid levels. Social support changes were measured over 1 year from baseline to follow-up round 1. Carotenoid level changes were established from follow-up round 1 to round 2. To determine whether or not regression to the mean was driving these results, we performed an analysis that included baseline and change levels of social support indicators. RESULTS: At baseline, the frequency of leaving one's home was associated with a decrease in carotenoid levels. Leaving one's home more frequently predicted an increase in carotenoid levels and attending fewer activities predicted a decrease in carotenoid levels. IMPLICATIONS: In older, community-resident disabled women, baseline levels of social support did not consistently predict diet quality. However, change in social support predicted both positive and negative change in diet quality and thus provides supportive evidence that social activity and family interaction may play meaningful roles in the maintenance of diet quality among functionally compromised older women. Further research is necessary to more fully understand the impact of multiple forms of social supports on the diet quality of older adults.

Advanced glycation end product level, diabetes, and accelerated cognitive aging.

OBJECTIVE: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. METHODS: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. RESULTS: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. CONCLUSION: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.

Plasma F2-isoprostane level and cognitive function over eight years in non-demented older adults: Findings from the Health ABC Study.

F2-isoprostanes (F2-IsoP) are reportedly increased in dementia patients, and are considered a reliable biomarker of oxidation. However, few studies have examined the predictive value of peripheral F2-IsoP levels in non-demented older adults. This study assesses the association between plasma F2-IsoP and change in cognitive function in non-demented elderly over eight years. Plasma F2-IsoP was measured by gas chromatography-mass spectrometry in a biracial cohort of 726 elderly men and women. Digit Symbol Substitution test and the Modified Mini-Mental State Exam were administered over time. No association was found between F2-IsoP tertile and baseline or change (slope) in cognitive function over eight years. Plasma F2-IsoP is not a valuable biomarker in predicting cognitive change over years in non-demented older adults.

Executive function, memory, and gait speed decline in well-functioning older adults.

BACKGROUND: In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS: Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS: Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS: In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

OBJECTIVE: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val(158)met) genotype and cognition in older adults. METHODS: We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined. RESULTS: Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]). CONCLUSION: These findings suggest that the Val allele has a protective impact on cognitive decline in late life.

Predictors of maintaining cognitive function in older adults: the Health ABC study.

BACKGROUND: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. METHODS: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope > or = 0), minor decliners (slope < 0 and > 1 SD below mean), or major decliners (slope < or = 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. RESULTS: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. CONCLUSION: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women.

Polypharmacy, common in older people, confers both risk of adverse outcomes and benefits. We assessed the relationship of commonly prescribed medications with anticholinergic and sedative effects to physical and cognitive performance in older individuals. The study population comprised 932 moderately to severely disabled community-resident women aged 65 years or older who were participants in the Women's Health and Aging Study I. A scale based on pharmacodynamic principles was developed and utilized as a measure of drug burden. This was related to measures of physical and cognitive function. After adjusting for demographics and comorbidities, anticholinergic drug burden was independently associated with greater difficulty in four physical function domains with adjusted odds ratios (95% confidence interval (CI)) of 4.9 (2.0-12.0) for balance difficulty; 3.2 (1.5-6.9) for mobility difficulty; 3.6 (1.6-8.0) for slow gait; 4.2 (2.0-8.7) for chair stands difficulty; 2.4 (1.1-5.3) for weak grip strength; 2.7 (1.3-5.4) for upper extremity limitations; 3.4 (1.7-6.9) for difficulty in activities of daily living; and 2.4 (95% CI, 1.1-5.1) for poor performance on the Mini-Mental State Examination. Sedative burden was associated only with impaired grip strength (3.3 (1.5-7.3)) and mobility difficulty (2.4 (1.1-5.3)). The burden of multiple drugs can be quantified by incorporating the recommended dose regimen and the actual dose and frequency of drug taken. Anticholinergic drug burden is strongly associated with limitations in physical and cognitive function. Sedative burden is associated with impaired functioning in more limited domains. The risk associated with exposure of vulnerable older women to drugs with anticholinergic properties, and to a lesser extent those with sedative properties, implies that such drugs should not be used in this patient group without compelling clinical indication.

Cognitive ability is associated with suspected reporting errors on food frequency questionnaires.

OBJECTIVE: To examine potential for bias in reported total energy intake on a Food Frequency Questionnaire (FFQ) among older adults. DESIGN: Longitudinal cohort study. SUBJECTS/SETTING: 2,706 Community-dwelling Black and White older adults, aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Multivariate logistic regression analyses were conducted with potential errors on reported total energy intake on the Food Frequency Questionnaire (FFQ) as the outcome variable and with cognitive ability, measured by the Modified Mini Mental State Exam (3MS) as the primary independent variable. The regression model controlled for site, race, gender, age, body size, and physical activity. Separate models were fit using 3MS as a continuous variable and for multiple 3MS cutpoints. All models revealed similar findings. RESULTS: Cognitive ability was inversely associated with potential errors in reporting total energy intake, whereby a five-point increase in 3MS scores was associated with a 14% decreased likelihood of reporting errors (Odds Ratio=0.86, 95% Confidence Interval: 0.77, 0.95). Additionally, compared to White women, White men were 2 times more likely, and Black women and Black men were 3 times more likely, to have errors in reporting total energy intake. CONCLUSION: This study provides evidence that for older adults, lower cognition scores are associated with increased potential errors in reporting total energy intake. APPLICATIONS: Dietary reporting from older adults may be inaccurate due to cognitive deficits. A brief assessment of cognitive function may assist clinicians in dietary evaluations and recommendation and may benefit studies using FFQ data where the measure of cognitive function could be utilized to stratify data analyses and conduct sensitivity analyses.

Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort.

BACKGROUND: Older women treated with conjugated estrogens may have an increased risk of dementia, but the effect of naturally occurring sex hormones on cognition is not certain. METHODS: Bioavailable estradiol and free testosterone level were obtained from 792 (55% men, 51% black) participants. We assessed cognition with the Modified Mini-Mental State Examination (3MS), Selective Reminding Test (SRT) and CLOX 1 at baseline and 2 years later. RESULTS: Women in the lowest estradiol tertile were more likely than those in the highest tertile to decline (> or = 1.0 S.D. of change) on 3MS (25% versus 9%, adjusted odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.6-9.6) and on SRT (28% versus 12%, adjusted OR [95% CI] = 3.3 [1.4-7.9]) but not CLOX 1. There was a borderline association between low estradiol tertile and decline on SRT in men (22% versus 14%, adjusted OR [95% CI] = 1.9 [0.9-3.9]). Testosterone level was not associated with decline in cognition in either men or women. Findings did not differ by race. CONCLUSIONS: Older women with low estradiol levels were more likely to experience decline in global cognitive function and verbal memory, and a similar trend was observed for verbal memory in men. This supports the hypothesis that endogenous sex hormones may play an important role in the maintenance of cognitive function in older adults.