Postmenopausal conjugated equine estrogens (CEE) therapies increase the risk of cognitive impairment in women aged 65 years or older and are associated with smaller regional brain volumes; however, the link between these two phenomena has not been established.
Standardized magnetic resonance imaging was performed on 1,403 women, 1–4 years after they had participated in randomized placebo-controlled clinical trials of CEE-based therapies. Women included in this report were aged 65–80 years and free of dementia and mild cognitive impairment (MCI) when originally enrolled in the trials, which lasted an average of 4–6 years and were conducted at 14 academic U.S. medical centers. The associations that regional brain volumes and ischemic lesion volumes had with the development of cognitive impairment (i.e., dementia or MCI) were contrasted between treatment groups using analyses of covariance.
Fifty-three women developed MCI or probable dementia during follow-up. Among women who had been prescribed CEE-based therapies, cognitive impairment was associated with relatively smaller hippocampal (p = .0002) and total brain volumes (p = .03). Qualitatively, these associations appeared to be independent of their level of pretreatment cognitive function. Among women who had been prescribed placebo, these relationships were not evident; instead, cognitive impairment was associated with greater ischemic lesion volume in the frontal lobe (p = .007) and overall (p = .02).
A mechanism by which CEE-based postmenopausal hormone therapy induces cognitive impairment appears to be through increased brain atrophy.
Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.
A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992–1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.
Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E 4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.
In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.
As our population ages, interventions that can prolong safe driving for older adults will be increasingly important.
Data from two studies were combined in order to investigate the effectiveness of cognitive training in delaying driving cessation. Stratified Cox hazard regressions were used to examine risk of driving cessation as a function of training participation, baseline driving, and visual acuity.
Older drivers with cognitive speed of processing difficulties who completed speed of processing training were 40% less likely to cease driving over the subsequent 3 years (hazard ratio = 0.596, 95% confidence interval 0.356–0.995, p = .048). Whereas 14% of older drivers who did not receive speed of processing training ceased driving, only 9% of those who completed eight or more sessions of speed of processing training ceased driving.
Speed of processing training may delay driving cessation among older drivers with speed of processing difficulty.
Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual’s ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging.
Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged ≥65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points.
Overall, there was a slight decline in DHEAS levels over time (–0.013 µg/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p < .001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32–2.33) and extreme variability (HR 1.89, CI 1.47–2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88–1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p < .001).
Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.
To determine whether Experience Corps (EC), a social service program, would improve age-vulnerable executive functions and increase activity in brain regions in a high-risk group through increased cognitive and physical activity.
Eight community-dwelling, older female volunteers and nine matched wait-list controls were recruited to serve in the ongoing EC: Baltimore program in three elementary schools. We employed functional magnetic resonance imaging (fMRI) preintervention and postintervention to examine whether EC volunteers improved executive function and showed increased activity in the prefrontal cortex relative to controls. fMRI volunteers were trained and placed with other volunteers 15 h/wk for 6 months during the academic year to assist teachers in kindergarten through third grade to promote children’s literacy and academic achievement.
Participants were African American and had low education, low income, and low Mini-Mental State Examination scores (M = 24), indicative of elevated risk for cognitive impairment. Volunteers exhibited intervention-specific increases in brain activity in the left prefrontal cortex and anterior cingulate cortex over the 6-month interval relative to matched controls. Neural gains were matched by behavioral improvements in executive inhibitory ability.
Using fMRI, we demonstrated intervention-specific short-term gains in executive function and in the activity of prefrontal cortical regions in older adults at elevated risk for cognitive impairment. These pilot results provide proof of concept for use-dependent brain plasticity in later life, and, that interventions designed to promote health and function through everyday activity may enhance plasticity in key regions that support executive function.
There is growing evidence that regular attendance at religious functions is associated with less cognitive decline (CD). However, little research has investigated factors that may moderate the religious attendance–CD relationship. The present study examined the effects of gender and depressive symptoms on the relationship between religious attendance and CD.
Data were drawn from waves 1 and 2 of the Duke Established Populations for Epidemiologic Studies of the Elderly, which were 3 years apart. Participants consisted of a sample of community-dwelling older adults aged 65 years and older (N = 2,938). Linear regression analyses were conducted controlling for important demographic-, socioeconomic-, and health-related variables. Cognitive functioning was assessed at both waves to examine change in errors over time.
Greater religious attendance was related to less CD. In addition, there was a three-way interaction between religious attendance, gender, and depressive symptoms in predicting CD. Among women with higher levels of depressive symptoms, those who less frequently attended religious services experienced greater CD than those who more frequently attended religious services. The interaction between attendance and depressive symptoms in men did not reach significance.
Religious attendance may offer mental stimulation that helps to maintain cognitive functioning in later life, particularly among older depressed women. Given the possible benefits religious attendance may have on cognitive functioning, it may be appropriate in certain instances for clinicians to recommend that clients reengage in religious activities they may have given up as a result of their depression.
Older adults who cease driving have poorer health than those who continue to drive. However, it is unclear whether the transition to driving cessation itself results in health declines or whether driving cessation subsequently exacerbates health declines over time.
The current study addresses these questions using multilevel modeling among 690 older adults from the Advanced Cognitive Training for Independent and Vital Elderly study. Driving status and health, as indicated by the SF-36 questionnaire, self-rated health, physical performance (Turn 360° Test), and depressive symptoms were assessed at baseline and at 1-, 2-, 3-, and 5-year follow-up visits.
The transition to driving cessation was accompanied by significant declines in physical and social functioning, physical performance, and physical role (ps < .05). Health declines after driving cessation were steeper for general health.
The transition to driving cessation is associated with health declines for older adults as measured by several indicators. Additionally, general health declines more sharply following driving cessation. These findings highlight the importance of interventions to sustain driving mobility among older adults.
The objective of this study was to identify the factors associated with recovery of prehospital function among older persons admitted to a nursing home with disability after an acute hospitalization.
The analytic sample included 292 participants of an ongoing cohort study who had one or more admissions to a nursing home with disability after an acute hospitalization during nearly 10 years of follow-up, yielding a total of 364 "index" nursing home admissions. Information on nursing home admissions, hospitalizations, and disability in essential activities of daily living was ascertained during monthly telephone interviews. Data on potential predictors of functional recovery were collected during comprehensive assessments, which were completed every 18 months for 90 months. Participants were considered to have recovered if they were discharged home within 6 months of their nursing home admission at (or above) their prehospital level of function.
Recovery of prehospital function was observed for 115 (31.6%) of the 364 index nursing home admissions. In the multivariate analysis, the strongest associations were observed for the best category of performance, relative to the poorest category, for gross motor coordination (hazard ratio [HR] 13.5, 95% confidence interval [CI] 4.02–45.0) and manual dexterity (HR 10.0, 95% CI 2.94–34.3). Only two other factors were independently associated with recovery of prehospital function: not cognitively impaired (HR 3.0, 95% CI 1.46–6.14) and no significant weight loss (HR 1.96, 95% CI 1.06–3.63).
In the setting of an acute hospitalization leading to a nursing home admission with disability, the likelihood of recovering prehospital function is low. The factors associated with recovery include faster performance on tests of gross motor coordination and manual dexterity and the absence of cognitive impairment and significant weight loss.
Balance during quiet stance involves the complex interactions of multiple postural control systems, which may degrade with frailty. The complexity of center of pressure (COP) dynamics, as quantified using multiscale entropy (MSE), during quiet standing is lower in older adults, especially those with falls. We hypothesized that COP dynamics from frail elderly individuals demonstrate less complexity than those from nonfrail elderly controls; complexity decreases when performing a dual task; and postural complexity during quiet standing is independent of other conventional correlates of balance control, such as age and vision.
We analyzed data from a population-based study of community-dwelling older adults. Frailty phenotype (nonfrail, prefrail, or frail) was determined for 550 participants (age 77.9 ± 5.5 years). COP excursions were quantified for 10 trials of 30 seconds each. Participants concurrently performed a serial subtraction task in half of the trials. Complexity of balance dynamics was quantified using MSE. Root-mean-square sway amplitude was also computed.
Of the 550, 38% were prefrail and 9% were frail. Complexity of the COP dynamics in the anteroposterior direction was lower in prefrail (8.78 ± 1.91 [mean ± SD]) and frail (8.38 ± 2.13) versus nonfrail (9.20 ± 1.74) groups (p < .001). Complexity reduced by a comparable amount in all three groups while performing the subtraction task (p < .001). Quiet standing complexity was independently associated with frailty after adjusting for covariates related to balance while sway amplitude was not.
Cognitive distractions during standing may further compromise balance control in frail individuals, leading to an increased risk of falls.
Cardiac autonomic dysfunction has been associated with cognitive impairment, but the underlying pathogenesis is complex and cerebral white matter lesions (WMLs) might be implicated.
Time and frequency heart rate variability (HRV) and visual rating of WMLs were carried out in 42 patients with mild cognitive impairment.
After adjustment for relevant demographic and clinical characteristics, including left ventricular mass, reduced HRV indices of parasympathetic (root mean square of successive difference of RR intervals, RMSSD) and sympathetic modulation (low-frequency [LF] power) were associated with increased WML score (RMSSD: B –0.30, 95% CI –0.52 to –0.08, p = .01; LF: B –0.24, 95% CI –0.46 to –0.02, p = .05). In a multiple-adjusted model, RMSSD was the major independent predictor of WMLs (B –0.35, 95% CI –0.57 to –0.13, p = .002).
The evidence for an independent association of cardiac autonomic dysfunction with WMLs might suggest its role in the pathogenesis of WMLs.
Hip pain (HP) and knee pain (KP) may specifically affect function and performance; few studies investigate the functional impact of HP or KP in the same population.
Population-based sample of older individuals living in the Chianti area (Tuscany, Italy) (1998–2000); 1006 persons (564 women and 442 men) were included in this analysis; 11.9% reported HP and 22.4% reported KP in the past 4 weeks. Self-reported disability and lower extremity performance, measured by 400-m walk test and by the short physical performance battery (SPPB, including standing balance, chair raising, and 4-m walk test), were compared in participants reporting HP or KP versus those free of these conditions; the relationship of HP or KP with performance and self-reported disability was studied, adjusting for age, sex, hip or knee flexibility, muscle strength, multiple joint pain, major medical conditions, and depression.
Participants reporting HP were more likely to report disability in shopping, cutting toenails, carrying a shopping bag, and using public transportation; those with KP reported more disability in cutting toenails and carrying a shopping bag. Participants reporting HP or KP had significantly lower SPPB scores. Adjusting by SPPB, pain no longer predicted self-reported disability, except for "HP—carrying a shopping bag."
In our cohort of older persons, those with HP reported disability in a wider range of activities than those with KP. Physical performance measured by SPPB was impaired in both conditions. Reduced lower extremity performance captures the excess disability associated with either HP or KP.
Although depressive symptoms in older persons are common, their association with disability burden is not well understood. The authors evaluated the association between level of depressive symptoms and severity of subsequent disability over time and determined whether this relationship differed by sex.
Participants included 754 community-living persons aged 70 years or older who underwent monthly assessments of disability in four essential activities of daily living for up to 117 months. Disability was categorized each month as none, mild, and severe. Depressive symptoms, assessed every 18 months, were categorized as low (referent group), moderate, and high. Multinomial logit models invoking Generalized Estimating Equation were used to calculate odds ratios and 95% confidence intervals.
Moderate (odds ratio = 1.30; 95% confidence interval: 1.18–1.43) and high (odds ratio = 1.68; 95% confidence interval: 1.50–1.88) depressive symptoms were associated with mild disability, whereas only high depressive symptoms were associated with severe disability (odds ratio = 2.05; 95% confidence interval: 1.76–2.39). Depressive symptoms were associated with disability burden in both men and women, with modest differences by sex; men had an increased likelihood of experiencing severe disability at both moderate and high levels of depressive symptoms, whereas only high depressive symptoms were associated with severe disability in women.
Levels of depressive symptoms below the threshold for subsyndromal depression are associated with increased disability burden in older persons. Identifying and treating varying levels of depressive symptoms in older persons may ultimately help to reduce the burden of disability in this population.
This study sought to determine whether the rates of basic activities of daily living (ADL) disabilities and functional limitations declined, remained the same, or increased between 2000 and 2005 when (a) only community-dwelling Americans aged 65 and older were examined and (b) when institutionalized older adults were included.
Using data from the American Community Survey and the National Nursing Home Survey, we calculated annual prevalence rates of basic ADL disabilities and functional limitations and fitted regression lines to examine trends over time.
The rates of basic ADL disabilities among community-dwelling adults aged 65 and older increased 9% between 2000 and 2005. When institutionalized elders were included, basic ADL disability rates were stable among men but increased among women. Functional limitation rates did not significantly change between 2000 and 2005.
These findings suggest an end of the decline in disability rates among older Americans, which, if confirmed, could have important implications for health care.