High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p<.001). Vascular and inflammatory factors influenced the association between BMI and FA. Specifically, BMI was independently associated with the genu [β=-.21; B=-.0024; 95% CI, -.0048 to -.0000; p=.05] and cingulate fibers [β=-.39; B=-.0035; 95% CI,-.0056 to -.0015; p<.001], even after controlling for vascular/inflammatory risk factors and blood markers. In contrast, BMI was no longer significantly associated with the fornix and middle/posterior regions of the corpus callosum after controlling for these markers. Results partially support a vascular/inflammatory hypothesis, but also suggest a more complex relationship between BMI and white matter characterized by potentially different neuroanatomic vulnerability.
Results of prospective studies examining the association between 25 hydroxyvitamin D
(25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis
that lower 25(OH)D levels are associated with a greater likelihood of cognitive
impairment and risk of cognitive decline.
The study is a cross-sectional and longitudinal analysis of a prospective cohort of
6,257 community-dwelling elderly women followed for 4 years. Global cognitive function
was measured by the Modified Mini-Mental State Examination and executive function was
measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was
defined as a score >1.5 SD below the sample mean; cognitive decline
was defined as decline from baseline to follow-up >1 SD from mean
change in score.
Women with very low vitamin D levels had an increased odds of global cognitive
impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05–2.42) for
women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels
≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL
(75 nmol/L), women with lower levels had an increased risk of global cognitive decline:
odds ratio (95% confidence interval), 1.58(1.12–2.22) for women with levels <10
ng/mL (25 nmol/L), and 1.31 (1.04–1.64) for those with levels 10–19.9 ng/mL
(25–49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive
Low 25(OH)D levels among older women were associated with a higher odds of global
cognitive impairment and a higher risk of global cognitive decline.
Vitamin D; Cognitive decline; Executive function; Cohort studies; Risk factors in epidemiology
Despite the high occurrence of depressive symptoms in older adults, especially women, little is known about the long-term course of late-life depressive symptoms.
To characterize the natural course of depressive symptoms among elderly women followed for nearly 20 years, going from young old to oldest old.
Using a latent class growth-curve analysis, we analyzed women enrolled in an ongoing prospective cohort study (1988–2009).
Clinic sites in Baltimore, MD, Minneapolis, MN, the Monongahela Valley near Pittsburgh, PA, and Portland, OR.
We studied 7240 community-dwelling women age 65 years or older.
Main Outcome Measure
The Geriatric Depression Scale (GDS) short form (range: 0–15) was used to assess depressive symptoms repeatedly over follow-up.
We identified four latent classes over 20 years, comprising an expected 28% of women with minimal depressive symptoms, 54% with persistently low symptoms, 15% with increasing symptoms, and 3% with persistently high symptoms. In an adjusted model for latent class membership, odds ratios (ORs) for belonging in the increasing and persistently high depressive symptom classes, respectively, compared with minimal symptom group were substantially and significantly (P < .05) elevated for baseline smoking (ORs, 4.69 and 7.97), physical inactivity (ORs, 2.11 and 2.78), small social network (ORs, 3.24 and 6.75), physical impairment (ORs, 8.11 and 16.43), myocardial infarction (ORs, 2.09 and 2.41), diabetes (ORs, 2.98 and 3.03), and obesity (ORs, 1.86 and 2.90).
Over 20 years, approximately 20% of older women experienced persistently high or increasing depressive symptoms. In addition, these women had more comorbidities, physical impairment, and negative lifestyle factors at baseline. These associations support the need for intervention and prevention strategies to reduce depressive symptoms into oldest-old years.
Identify the neuroimaging correlates of parkinsonian signs in older adults living in the community.
Magnetic resonance imaging was obtained in 307 adults (82.9 years, 55% women, 39% blacks) concurrently with the Unified Parkinson Disease Rating scale—motor part. Magnetic resonance imaging measures included volume of whole-brain white matter hyperintensities and of gray matter for primary sensorimotor, supplementary motor, medial temporal areas, cerebellum, prefronto-parietal cortex, and basal ganglia.
About 25% of the participants had bradykinesia, 26% had gait disturbances, and 12% had tremor. Compared with those without, adults with any one of these signs were older, walked more slowly, had worse scores on tests of cognition, mood and processing speed, and higher white matter hyperintensities volume (all p ≤ .002). Gray matter volume of primary sensorimotor area was associated with bradykinesia (standardized odds ratio [95% confidence interval]: 0.46 [0.31, 0.68], p < .0001), and gray matter volume of medial temporal area was associated with gait disturbances (0.56 [0.42, 0.83], p < .0001), independent of white matter hyperintensities volume and age. Further adjustment for measures of muscle strength, cardiovascular health factors, cognition, processing speed, and mood or for gait speed did not substantially change these results.
Atrophy within primary sensorimotor and medial temporal areas might be important for development of bradykinesia and of gait disturbances in community-dwelling elderly adults. The pathways underlying these associations may not include changes in white matter hyperintensities volume, cognition, information processing speed, mood, or gait speed.
Bradykinesia; Gait disturbances; Brain MRI
While several studies report an association between prevalent diabetes mellitus (DM) and cognitive impairment, less is known about incident DM in late life and cognitive decline. Glycemic control among elders with DM may also be associated with cognitive function, but findings are inconsistent.
To determine if prevalent and incident DM increases risk of cognitive decline, and if, among elders with DM, poor glucose control is related to worse cognitive performance.
Prospective cohort study.
Health Aging and Body Composition Study at two community clinics.
A total of 3,069 elders (mean age 74.2 years; 42% black; 52% female).
Main Outcome Measures
Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. DM status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A1c (HbA1c) was measured at year 1 (baseline), 4, 6, and 10 from fasting whole blood.
At baseline 717 (23.4%) participants had prevalent DM and 2352 (76.6%) were without diabetes, 159 of whom developed incident DM during follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM (3MS: 88.8 vs. 90.9; DSST: 32.5 vs 36.3, respectively; |t|=6.09, p=0.001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: −6.0 vs. −4.5 point decline; |t|=2.66, p=0.008; DSST: −7.9 vs. −5.7, point decline; |t|=3.69, p=0.001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other two groups but were not statistically different from the group without diabetes. Multivariate adjustment for demographics and medical co-morbidities produced similar results. Among participants with prevalent DM, HbA1c level was associated with lower average mean cognitive scores (3MS p for overall=0.003; DSST p for overall=0.04), even after multivariate adjustment.
Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests severity of DM may contribute to accelerated cognitive aging.
To determine if less severe depression spectrum diagnoses such as dysthymia, as well as depression, are associated with risk of developing dementia and mortality in a “real world” setting.
Retrospective cohort study conducted using the Department of Veterans Affairs (VA) National Patient Care Database (1997-2007).
VA medical centers in the United States.
A total of 281,540 veterans 55 years and older without dementia at study baseline (1997-2000).
Depression status and incident dementia were ascertained from ICD-9 codes during study baseline (1997-2000) and follow-up (2001-2007), respectively. Mortality was ascertained by time of death dates in the VA Vital Status File.
Ten percent of veterans had baseline diagnosis of depression and nearly 1% had dysthymia. The unadjusted incidence of dementia was 11.2% in veterans with depression, 10.2% with dysthymia and 6.4% with neither. After adjusting for demographics and comorbidities, patients diagnosed with dysthymia or depression were twice as likely to develop incident dementia compared to those with no dysthymia/depression (adjusted dysthymia hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.71-2.25; and depression HR: 2.18, 95% CI: 2.08-2.28). Dysthymia and depression also were associated with increased risk of death (31.6% dysthymia and 32.9% depression vs 28.5% neither; adjusted dysthymia HR: 1.41, 95% CI: 1.31-1.53; and depression HR: 1.47, 95% CI: 1.43-1.51).
Findings suggest that older adults with dysthymia or depression need to be monitored closely for adverse outcomes. Future studies should determine whether treatment of depression spectrum disorders may reduce risk of these outcomes.
Dysthymia; Depression; Dementia; Mortality
Maintaining cognitive function protects older adults from developing functional decline. This study aims to identify the neuroimaging correlates of maintenance of higher global cognition as measured by the Modified Mini Mental State Test (3MS) score.
Repeated 3MS measures from 1997–98 through 2006–07 and magnetic resonance imaging with diffusion tensor in 2006–07 were obtained in a biracial cohort of 258 adults free from dementia (mean age 82.9 years, 56% women, 42% blacks). Participants were classified as having shown either maintenance (3MS slope>0) or decline (3MS slopeb1 SD below the mean) of cognition using linear mixed models. Measures of interest were white matter hyperintensity volume (WMHv) from total brain, volume of the gray matter (GMv) and microstructure (mean diffusivity, MD) for total brain and for brain areas known to be related to memory and executive control function: medial temporal area (hippocampus, parahippocampus and entorhinal cortex), cingulate cortex, dorsolateral prefrontal and posterior parietal cortex.
Differences between cognitive maintainers (n=153) and non-maintainers (n=107) were significant for GMv of the medial temporal area (35.8%, p=0.004) and lower MD of the cingulate cortex (37.9%, p=0.008), but not for other neuroimaging markers. In multivariable regression models adjusted for age, race, WMHv and GMV from the total brain and vascular conditions, each standard deviation of GMv of the medial temporal area and each standard deviation of MD of the cingulate cortex were associated with a nearly 4 times greater probability (odds ratio [standard deviation]: 3.80 [1.16, 12.44]) and a 34% lower probability (0.66, [0.46, 0.97]) of maintaining cognitive function, respectively. In these models neither WMHv nor GMv from total brain were significantly associated with probability of maintaining cognitive function.
Preserving the volume of the medial temporal area and the microstructure of the cingulate cortex may contribute to maintaining cognitive function late in life.
It is unclear why late-life mood and anxiety disorders are highly undertreated, despite being common in older adults. Thus, this study determined the prevalence and key factors associated with non-use of mental health services among older community-dwelling adults with mood and anxiety disorders.
The study examined 348 participants aged 55 years and older who met criteria for prevalent DSM-IV mood and anxiety disorders from the National Comorbidity Survey Replication (NCS-R), a population-based probability sample. Analyses included frequency measures and logistic regression using weights and complex design-corrected statistical tests. Key factors associated with not using mental health services were determined in a final multivariable model using a systematic approach accounting for a comprehensive list of potential predictors.
Approximately 70% of older adults with prevalent mood and anxiety disorders did not use services. Those who were from minority race/ethnic groups, not comfortable with discussing personal problems, who were married or cohabitating, and middle versus high income status had increased odds of not using mental health services. In addition, respondents with mild versus serious disorders, no chronic pain complaints, and low versus high perceived cognitive impairment had greater odds of non-use.
The results support improving perception of need and comfort to seek help, as well as increased screening and other prevention efforts, in order to combat the very high number of mood and anxiety disorders that go untreated in older Americans.
Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican-Americans have higher levels of obesity than Non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association.
We analyzed 1480 dementia-free older Mexican-Americans who were followed over ten years. Cognitive function was assessed every 12 to 15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT).
For females with small waist circumference (≤35inches), an interquartile range (IQR) difference in leptin was associated with 35% less 3MSE errors and 22% less decline in SEVLT score over 10 years. For males with small waist circumference (≤40inches), an IQR difference in leptin was associated with 44% less 3MSE errors and 30% less decline in SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with large waist circumference.
Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function.
Aging; cognition; obesity; leptin; longitudinal study; Mexican Americans
Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia.
Objective, Design, Setting and Participants
To clarify the timing and etiology of the association, we examined depressive symptoms assessed in mid-life (1964–1973) and late-life (1994–2000) and the risks of dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) (2003–2009) in a retrospective cohort study of 13,535 long-term Kaiser Permanente members. Depressive symptoms were categorized as none, mid-life only, late-life only or both. Cox proportional hazards models (age as time-scale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD or VaD.
Main Outcome Measure
Any medical record diagnosis of dementia; Neurology clinic diagnosis of AD or VaD.
Subjects had a mean (standard deviation) age of 81 (5) years in 2003; 58% were women and 25% were non-white. Depressive symptoms were present in 14.1% of subjects in mid-life only, 9.2% late-life only, and 4.2% both. Over 6 years, 23.1% were diagnosed with dementia (5.5% AD, 2.3% VaD). The adjusted hazard of dementia was increased by approximately 20% for mid-life depressive symptoms only (Hazard Ratio [95% confidence interval]: 1.19 [1.07, 1.32]), 70% for late-life symptoms only (1.72 [1.54, 1.92]), and 80% for both (1.77 [1.52, 2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a two-fold increase in AD risk (2.06 [1.67, 2.55]) whereas subjects with both mid-life and late-life symptoms had more than a three-fold increase in VaD risk (3.51 [2.44, 5.05]).
Depressive symptoms in mid-life or late-life are associated with an increased risk of developing dementia. Depression that begins in late-life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.
Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.
Settings and Participants
Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008.
Depressive symptoms measured by Beck Depression Inventory (BDI)
Demographic and clinical factors
Elevated depressive symptoms (BDI >= 11) and antidepressant medication use
Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each).
Absence of clinical diagnosis of depression and use of non-pharmacologic treatments
Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. African Americans, Hispanics, and individuals with more advanced CKD had higher odds of elevated depressive symptoms and lower odds of antidepressant medication use.
To determine the association between objectively measured sleep and subsequent placement in a nursing home or a personal care home.
Homes of participants in an ongoing study
1,664 community-dwelling women, mean age 83 ±4 years
At baseline, participants completed an average of 4 nights of wrist actigraphy; they provided data on place of residence at baseline and at follow-up, 5 years later.
At baseline, participants had a mean total sleep time of 408 ±72 minutes, mean wake after sleep onset of 71±43 minutes, and mean sleep efficiency of 79 ±11 percent. At follow-up, 71 (4%) were residing in a nursing home and 127 (8%) were in a personal care home. Compared to women with the least wake after sleep onset (by quartile), those with the most had more than twice the odds of placement in a nursing home (adjusted odds ratio (AOR) = 2.94, 95% confidence interval (CI) 1.34, 6.44) or a personal care home (AOR = 2.33, 95% CI 1.26, 4.30). Similarly, compared to women with the highest sleep efficiency, those with the lowest had more than three times the odds of nursing home placement (AOR = 3.25, 95% CI 1.35, 7.82) and more than twice the odds of placement in a personal care home (AOR = 2.38, 95% CI 1.33, 4.24). There was no association between sleep duration and placement.
Among very old community-dwelling women, greater wake after sleep onset and lower sleep efficiency are risk factors for placement in a nursing home or personal care home. Sleep duration alone does not appear to increase the risk of placement in these long-term care settings.
sleep; actigraphy; nursing home; placement; women
We determined the pattern of clinically significant cognitive impairment (CI) among older veterans with Post Traumatic Stress Disorder (PTSD) evaluated in a memory disorders clinic.
Data was collected from 19 ethnically diverse veterans. Cognitive functioning in six domains (verbal learning, memory, attention, language, executive functioning, and information processing speed) was assessed.
The majority of veterans (57%) demonstrated CI on a measure of single trial list learning, 44% exhibited CI on short delay memory for lists, and 31% exhibited CI in long delay memory for lists. CI on measures of memory for stories (14%) and executive functioning (6%) were less common and none of the participants demonstrated CI on measures of attention, language, or information processing speed.
CI on measures of single trial list learning and memory for lists are common in older PTSD patients evaluated in a memory disorders clinic and are likely to contribute to functional deficits.
Cognitive deficits; cognitive impairment; Post Traumatic Stress Disorder; older adults; veterans; memory; learning; single trial learning; executive dysfunction; information processing speed; attention; language
There is increasing evidence from basic science and human epidemiological studies that
inflammation, oxidative stress, and metabolic abnormalities are associated with
age-related cognitive decline and impairment. This article summarizes selected research on
these topics presented at the Cognitive Aging Summit II. Speakers in this session
presented evidence highlighting the roles of these processes and pathways on age-related
cognitive decline, pointing to possible targets for intervention in nondemented older
adults. Specific areas discussed included age differences in the production of cytokines
following injury or infection, mechanisms underlying oxidative stress-induced changes in
memory consolidation, insulin effects on brain signaling and memory, and the association
between metabolic syndrome and cognitive decline in older adults. These presentations
emphasize advances in our understanding of mechanisms and modifiers of age-related
cognitive decline and provide insights into potential targets to promote cognitive health
in older adults.
Aging; Cognition; Inflammation; Oxidative stress; Metabolism
It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen’s d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.
To determine whether objectively measured sleep quality predicts five-year incident instrumental activities of daily living (IADL) impairment and decline in grip strength and gait speed in older women.
Participants’ homes, Study of Osteoporotic Fractures sites
817 women (mean 82.4 years at baseline)
Participants completed 4.1 ±0.7 nights of wrist actigraphy at baseline, and measures of IADL impairment, grip strength, and gait speed at baseline and five-year follow-up.
After five years of follow-up, approximately 41% of participants had incident impairment in ≥1 IADL. The quartile of women with the shortest total sleep time had a 93% greater odds of incident IADL impairment than the longest sleepers (adjusted odds ratio (AOR) = 1.93, 95% confidence interval (CI) 1.25, 2.97). Similarly, the quartile of women with the lowest sleep efficiency had a 65% greater odds of impairment than those with the highest (AOR = 1.65, 95% CI 1.06, 2.57). Women in the shortest total sleep time quartile had double the odds of declining grip strength, compared to those with the longest total sleep time (AOR = 1.97, 95% CI 1.17, 3.32). Finally, women in the quartiles with the most wake after sleep onset and the lowest sleep efficiency had an approximately 90% greater odds of grip strength decline than those with the least wake after sleep onset (AOR = 1.90, 95% CI 1.11, 3.24) and sleep efficiency (AOR = 1.92, 95% CI 1.12, 3.29).
Findings indicate that shorter sleep duration, greater wake after sleep onset, and lower sleep efficiency are risk factors for functional or physical decline in older women.
sleep; actigraphy; function; IADLs; women
To examine whether deficient B12 status or low serum B12 levels are associated with worse sensory and motor peripheral nerve function in older adults.
Health, Aging and Body Composition Study.
Two thousand two hundred eighty-seven adults aged 72–83 years [mean age: 76.5 ± 2.9 years; 51.4% female; 38.3% black].
Low serum B12 was defined based solely on serum B12 of <260 pmol/L, whereas deficient B12 status was defined as B12 <260 pmol/L, methylmalonic acid [MMA] >271 nmol/L and MMA >2-methylcitrate. Peripheral nerve function was assessed by peroneal nerve conduction amplitude and velocity [NCV] (motor); 1.4g/10g monofilament detection; average vibration threshold detection; and peripheral neuropathy symptoms [numbness; aching/burning pain] (sensory).
B12 deficient status was found in 7.0% and an additional 10.1% had low serum B12 levels. B12 deficient status was associated with greater insensitivity to light (1.4g) touch (OR: 1.50; 95% CI: [1.06, 2.13]) and worse NCV [42.3 m/s vs. 43.5 m/s] (β =−1.16; p=0.01), after multivariable adjustment for demographics, lifestyle factors, and health conditions. Associations were consistent for the alternative definition using low serum B12 only. No significant associations were found for deficient B12 status or the alternative low serum B12 definition and vibration detection, nerve conduction amplitude, or peripheral neuropathy symptoms.
Poor B12 (deficient B12 status and low serum B12) is associated with worse sensory and motor peripheral nerve function. Nerve function impairments may lead to physical function declines and disability in older adults, suggesting that prevention and treatment of low B12 levels may be important to evaluate.
low B12; deficient B12; sensory peripheral nerve function; motor nerve conduction; older adults
To determine how physical activity at various ages over the life course is associated with cognitive impairment in late life.
Four US sites.
We administered a modified Mini-Mental State Examination (mMMSE) to 9344 women ≥65 years (mean 71.6 years) who self-reported teenage, age 30, age 50, and late life physical activity.
We used logistic regressions to determine the association between physical activity status at each age and likelihood of cognitive impairment (mMMSE score >1.5SD below the mean, mMMSE≤22). Models were adjusted for age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and body mass index.
Women who reported being physically active had lower prevalence of cognitive impairment in late life compared to women who were inactive at each time (teenage: 8.5% vs. 16.7%; adjusted Odds Ratio (95% Confidence Interval): 0.65 (0.53–0.80); age 30: 8.9% vs. 12.0%; 0.80 (0.67–0.96); age 50: 8.5% vs. 13.1%; 0.71 (0.59–0.85); old age: 8.2% vs. 15.9%; 0.74 (0.61–0.91)). When the four times were analyzed together, teenage physical activity was most strongly associated with lower odds of late-life cognitive impairment (OR=0.73 (0.58–0.92)). However, women who were physically inactive at teenage and became active in later life had lower risk than those who remained inactive.
Women who reported being physically active at any point over the life course, and especially at teenage, have lower likelihood of cognitive impairment in late life. Interventions should promote physical activity early in life and throughout the life course.
Physical Activity; Exercise; Cognition; Cognitive Impairment; Life Course
To examine the relationship between depressive symptoms and subjective and objective sleep in older women.
Four US clinical centers.
3045 community-dwelling women ≥70 years.
Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as “normal” (0–2, referent), “some depressive symptoms” (3–5), or “depressed” (≥6). Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Objective sleep measures were assessed with wrist actigraphy.
In multivariable-adjusted models, there were graded associations between increased level of depressive symptoms and both worse subjective sleep quality and more subjective daytime sleepiness (p-trends <0.001). Women with some depressive symptoms (OR 1.82, CI 1.48–2.24) and depressed (OR 2.84, CI 2.08–3.86) women had greater odds of reporting poor sleep (PSQI>5). Women with some depressive symptoms (OR 1.97, CI 1.47–2.64) and depressed women (OR 1.70, CI 1.12–2.58) had greater odds of reporting excessive daytime sleepiness (ESS>10). There were also graded associations between increased level of depressive symptoms and objectively measured wake after sleep onset (WASO) (p-trend = 0.030) and long wake episodes >5 minutes (p-trend 0.006). Depressed women had modestly increased odds of WASO ≥1 hour (OR 1.37, CI 1.03–1.83). Women with some depressive symptoms (OR 1.49, CI 1.19–1.86) and depressed women (OR 2.04, CI 1.52–2.74) had greater odds of being in the highest quartile for number of nap episodes >5 minutes. No associations between depressive symptom level and prolonged sleep latency, reduced sleep efficiency, or reduced or increased total sleep time were found.
Greater depressive symptom levels were associated with more subjective sleep disturbance and objective evidence of sleep fragmentation and napping.
Depression; sleep; actigraphy; elderly; age
Sleep-disordered breathing (SDB), characterized by recurrent arousals from sleep and intermittent hypoxemia, is common among older adults. Cross-sectional studies have linked SDB to poor cognition; however, it remains unclear whether sleep disordered breathing precedes cognitive impairment in older adults.
To determine the prospective relationship between sleep disordered breathing and cognitive impairment and to investigate potential mechanisms of this association.
Design, Setting, and Participants
Prospective sleep and cognition study of 298 women without dementia (mean [SD] age: 82.3 [3.2] years) who had overnight polysomnography (PSG) measured between January 2002 and April 2004 in a substudy of the Study of Osteoporotic Fractures. Sleep disordered breathing was defined as an apnea-hypopnea index of 15 or more events per hour of sleep. Multivariate logistic regression was used to determine the independent association of sleep disordered breathing with risk of mild cognitive impairment or dementia and adjustments were made for age, race, body mass index, education, smoking status, presence of diabetes, presence of hypertension, medication use (antidepressants, benzodiazepines, or non-benzodiazepine anxiolytics), and baseline cognitive scores. Measures of hypoxia, sleep fragmentation, and sleep duration were investigated as underlying mechanisms for this relationship.
Main Outcome Measures
Adjudicated cognitive status (normal, dementia, or mild cognitive impairment [MCI]) based on data collected between November 2006 and September 2008
Compared with the 193 women without sleep disordered breathing, the 105 women (35.2%) with SDB were more likely to develop MCI/dementia (n=60 (31.1%) vs n=47 (44.8%)) even after multivariate adjustment (adjusted OR=1.85, 95% CI 1.11-3.08). Elevated oxygen desaturation index (≥15 events/hour) and high percentage (>7%) of sleep time in apnea or hypopnea, both measures of disordered breathing, were associated with risk of developing MCI/dementia (adjusted OR=1.71, 95% CI 1.04 − 2.83 and adjusted OR=2.04, 95% CI 1.10 − 3.78, respectively). Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.
Among older women, those with sleep disordered breathing, compared with those without SDB, were associated with an increased risk of developing cognitive impairment.
Recent research suggests a central role for inflammatory mechanisms in cognitive decline that may occur prior to evidence of neurodegeneration. Limited information exists, however, regarding the relationship between low-grade inflammation and cognitive function in healthy older adults. This study examined the relation between inflammation, verbal memory consolidation, and medial temporal lobe volumes in a cohort of older community-dwelling subjects. Subjects included 141 functionally intact, community dwelling older adults with detectable (n = 76) and undetectable (n= 65) levels of C-reactive protein. A verbal episodic memory measure was administered to all subjects, and measures of delayed recall and recognition memory were assessed. A semiautomated parcellation program was used to analyze structural MRI scans. On the episodic memory task, analysis of covariance revealed a significant CRP group by memory recall interaction, such that participants with detectable levels of CRP evidenced worse performance after a delay compared to those with undetectable levels of CRP. Individuals with detectable CRP also demonstrated lower performance on a measure of recognition memory. Imaging data demonstrated smaller left medial temporal lobe volumes in the detectable CRP group as compared with the undetectable CRP group. These findings underscore a potential role for inflammation in cognitive aging as a modifiable risk factor.
inflammation; memory; aging; cognition; temporal lobe; c-reactive protein; cytokines
Stiffness of the central arteries in aging may contribute to cerebral microvascular disease independent of hypertension and other vascular risk factors. Few studies of older adults have evaluated the association of central arterial stiffness with longitudinal cognitive decline.
We evaluated associations of aortic pulse wave velocity (centimeters per second), a measure of central arterial stiffness, with cognitive function and decline in 552 participants in the Health, Aging, and Body Composition (Health ABC) study Cognitive Vitality Substudy (mean age ± SD = 73.1 ± 2.7 years, 48% men and 42% black). Aortic pulse wave velocity was assessed at baseline via Doppler-recorded carotid and femoral pulse waveforms. Global cognitive function, verbal memory, psychomotor, and perceptual speed were evaluated over 6 years.
After adjustment for demographics, vascular risk factors, and chronic conditions, each 1 SD higher aortic pulse wave velocity (389 cm/s) was associated with poorer cognitive function: −0.11 SD for global function (SE = 0.04, p < .01), −0.09 SD for psychomotor speed (SE = 0.04, p = .03), and −0.12 SD for perceptual speed (SE = 0.04, p < .01). Higher aortic pulse wave velocity was also associated with greater decline in psychomotor speed, defined as greater than 1 SD more than the mean change (odds ratio = 1.42 [95% confidence interval = 1.06, 1.90]) but not with verbal memory or longitudinal decline in global function, verbal memory, or perceptual speed. Results were consistent with mixed models of decline in each cognitive test.
In well-functioning older adults, central arterial stiffness may contribute to cognitive decline independent of hypertension and other vascular risk factors.
Aging; Arterial stiffness; Cognitive decline
To examine the association of sleep architecture, sleep disordered breathing, and cognition in older men.
A population-based cross-sectional study.
6 sites in the United States.
2,909 community-dwelling men age 67 or older who were not selected on the basis of sleep problems or cognitive impairment.
Predictors were measured with in-home polysomnography: sleep architecture, nocturnal hypoxemia (any sleep time with SaO2<80%), apnea-hypopnea index (AHI), and arousal index. Cognitive outcomes were measured by the Modified Mini-Mental State Examination (3MS), Trails B test, and the Digit Vigilance Test (DVT).
Analyses adjusted by age, race, education, BMI, lifestyle, comorbidities and medication use show that those who spent less percent of time in rapid eye movement (REM) sleep had worse levels of cognition: compared to the highest quartile (≥23.7%), those in the lowest quartile (<14.8%) took an average of 5.9 seconds longer on the Trails B and 20.1 seconds longer on the DVT. Similarly, increased percent time spent in stage 1 sleep was related to poorer cognitive function. Those in the highest quartile of stage 1 sleep (≥8.6%) had worse cognitive scores on average compared to those in the lowest quartile (<4.0%). Those with nocturnal hypoxemia took longer to complete the DVT by an average of 22.3 seconds compared to those without, but no associations were found with 3MS or Trails B.
Spending less percent of time spent in REM sleep, more percent of time spent in stage 1 sleep, and having higher levels of nocturnal hypoxemia were associated with poorer cognition in older men. Further studies are needed to clarify the direction of these associations and to explore potential mechanisms.
sleep architecture; sleep disordered breathing; cognitive function; hypoxemia
Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).
Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, BMI, functional status, depression, medications, alcohol, caffeine, smoking, health status, and co-morbidities.
After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (Odds ratio[OR]=1.57,95% CI,1.09–2.25) or rhythm robustness (OR=1.57,95%CI,1.10–2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR=1.83,95% CI,1.29–2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51PM) when compared to those with average timing (1:34PM–3:51PM).
Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly.