Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration.

BACKGROUND: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. METHODS: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. RESULTS: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. CONCLUSIONS: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.

Mediation Analyses of the Role of Apathy on Motoric Cognitive Outcomes.

Recent literature indicates that apathy is associated with poor cognitive and functional outcomes in older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome. However, the underlying biological pathway is unknown. The objectives of this study were to (1) examine the cross-sectional associations between inflammatory cytokines (Interleukin 6 (IL-6) and C-Reactive Protein (CRP)) and apathy and (2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes as it relates to important cognitive risk factors. N = 347 older adults (≥65 years old) enrolled in the Central Control of Mobility in Aging Study (CCMA). Linear and logic regression models showed that IL-6, but not CRP was significantly associated with apathy adjusted for age, gender, and years of education (ß = 0.037, 95% CI: 0.002-0.072, p = 0.04). Apathy was associated with a slower gait velocity (ß = -14.45, 95% CI: -24.89-4.01, p = 0.01). Mediation analyses demonstrated that IL-6 modestly mediates the relationship between apathy and gait velocity, while apathy mediated the relationships between dysphoria and multimorbidity and gait velocity. Overall, our findings indicate that apathy may be an early predictor of motoric cognitive decline. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.

Computerised cognitive remediation to enhance mobility in older adults: a single-blind, single-centre, randomised trial.

BACKGROUND: Decline in executive functions and related cognitive processes is associated with mobility decline, and these functions might be amenable to cognitive remediation. This study aimed to examine whether a computerised cognitive remediation programme would improve walking in adults aged 70 years and older. METHODS: This single-blind, randomised trial at one academic centre in the USA evaluated the efficacy of an 8-week computerised programme (also known as brain games) of progressive intensity and complexity to improve walking in older adults at high-risk for mobility disability. Inclusion criteria included being 70 years or older; ambulatory; and at high-risk for mobility disability, defined using a cutscore of nine or less (frail range) on the Short Physical Performance Battery and a walking speed of 100 cm/s or less. Individuals with dementia, acute or terminal medical illnesses, recent or planned surgery affecting mobility, mobility limitations solely due to musculoskeletal limitation or pain that prevented them from completing mobility tests, and those who were nursing home residents were excluded. Participants were block randomised (1:1; block size 12 and no stratification) to the intervention group or the control group (low complexity computer games and health education classes). Primary outcomes were change in walking speed at normal pace and walking while talking conditions assessed from baseline to 8 weeks post-intervention by investigators who were masked to group assignment. Groups were compared using the intention-to-treat principle with linear mixed models adjusted for confounders. This trial was registered with ClinicalTrails.gov, NCT02567227. FINDINGS: Between March 1, 2016, and March 12, 2020, 383 patients were enrolled and randomly assigned to the intervention or control group. After randomisation, 11 (3%) patients were diagnosed with dementia. 372 (97%; 271 [73%] women) were included in the intention-to-treat analysis. The mean age of participants was 77·0 years [SD 5·6]). 183 (49·2%) participants were Black and 62 (16·7%) were Hispanic. 314 (93%) of the target 338 completers had finished the intervention when the trial was terminated due to the COVID-19 pandemic. Although there were significant within-group improvements in both groups after the 8-week intervention, there was no significant difference in normal walking speed (-1·03 cm/s [SD 1·30]; 95% CI -3·60 to 1·54) and walking while talking conditions (0·59 cm/s [SD 1·61]; 95% CI -2·59 to 3·76) between the intervention and control groups. Similarly, within-group, but no between-group, differences were seen on executive function tests and physical function. There were no severe adverse events related to interventions. INTERPRETATION: Computerised cognitive remediation improved walking in adults aged 70 years and older at high-risk for mobility disability, but improvements were not significantly greater compared with an active control. Although our findings corroborate the within-group improvements on cognition and mobility reported in previous pilot clinical trials, future studies are required to determine the optimal dose, frequency, intensity, and content of computerised cognitive remediation programmes. FUNDING: National Institute on Aging.

Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults.

While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults (n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05-1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680-0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08-2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004-1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29-0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span.

Motoric Cognitive Risk Syndrome in Polypharmacy.

OBJECTIVES: Risk factors for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, have been identified, but few are reversible. Polypharmacy is a potentially reversible risk factor for cognitive decline, but the relationship between MCR and polypharmacy has not been examined. Our aim was to compare the epidemiology of MCR and polypharmacy. DESIGN: Cross-sectional. SETTING: Community-based Health and Retirement Study cohort. PARTICIPANTS: A total of 1119 adults 65 years and older (mean age = 74.7 ± 7.0 y; 59% female). MEASUREMENTS: Polypharmacy is defined as the use of five or more regularly scheduled medications. MCR is defined as cognitive complaints and slow gait in an individual without dementia. RESULTS: The prevalence of MCR among 417 participants with polypharmacy was 10%; it was 6% among 702 participants without polypharmacy. The odds of meeting MCR criteria in those with polypharmacy was 1.8 (confidence interval = 1.0-3.0; P = .035) compared with those without polypharmacy, even after adjusting for high-risk medication use. CONCLUSION: Our results show the coexistence of MCR and polypharmacy in older adults, suggesting a potentially modifiable risk factor for dementia. J Am Geriatr Soc 68:1072-1077, 2020.

Physical Activity and Risk of Postoperative Delirium.

BACKGROUND/OBJECTIVE: Regular physical activity (PA) has been associated with improved cognitive function, but its effect on postoperative delirium (POD) has not been established. Our objectives were to determine the effect of baseline PA on the incidence of POD in older patients undergoing elective orthopedic surgery and to determine whether these effects were independent of cognitive reserve. We hypothesize that PA protects against POD by bolstering physiologic reserve needed to withstand the stressors of surgery. DESIGN: Secondary analysis of a prospective, single-center, cohort study. SETTING: Urban academic hospital. PARTICIPANTS: A total of 132 nondemented, English-speaking adults older than 60 years undergoing elective orthopedic surgery. MEASUREMENTS: Subjects were screened for POD and delirium severity using the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Baseline cognitive activities and PAs were assessed with a validated Leisure Activity Scale. Regular PA was categorized as 6 to 7 days per week. The association of regular PA with incidence of POD was assessed using multivariable logistic regression, adjusting for age, sex, Charlson Comorbidity Index, cognitive reserve, and cognitive function. Linear regression was used to assess the association of delirium severity with regular PA. RESULTS: Of 132 patients, 41 (31.1%) developed POD. Regular PA was associated with a 74% lower odds of developing POD (odds ratio [OR] = 0.26; 95% confidence interval [CI] = 0.08-0.82). There was no significant interaction between PA and cognitive reserve (P = .70). Of 85 women, 25 (29.4%), and of 47 men, 16 (34.0%) developed POD. In stratified analysis, women who engaged in regular PA had dramatically lower odds of POD (OR = 0.08; 95% CI = 0.01-0.63) compared with men (OR = 0.93; 95% CI = 0.18-4.97). CONCLUSIONS: Regular PA is associated with decreased incidence of POD, especially among women. Future studies should address the basis of sex differences in PA benefits on delirium. J Am Geriatr Soc 67:2260-2266, 2019.

Apolipoprotein E Polymorphism and Oxidative Stress in Peripheral Blood-Derived Macrophage-Mediated Amyloid-Beta Phagocytosis in Alzheimer's Disease Patients.

Peripheral blood-derived macrophages isolated from Alzheimer's disease (AD) patients have earlier been reported to demonstrate ineffective phagocytosis of amyloid-beta compared to the age-matched control subjects. However, the mechanisms causing unsuccessful phagocytosis remain unclear. Oxidative stress and the presence of ApoEε4 allele has been reported to play a major role in the pathogenesis of AD, but the contribution of oxidative stress and ApoEε4 in macrophage dysfunction leading to ineffective Aß phagocytosis needs to be analyzed. Aß phagocytosis assay has been performed using FITC-labeled Aß and analyzed using flow cytometry and confocal imaging in patient samples and in THP-1 cells. Oxidative stress in patient-derived macrophages was analyzed by assessing the DNA damage using comet assay. ApoE polymorphism was analyzed using sequence-specific PCR and Hixson & Vernier Restriction isotyping protocol. In this study, we have analyzed the patterns of phagocytic inefficiency of macrophages in Indian population with a gradual decline in the phagocytic potential from mild cognitive impairment (MCI) to AD patients. Further, we have shown that the presence of ApoEε4 allele might also have a possible effect on the phagocytosis efficiency of the macrophages. Here, we demonstrate for the first time that oxidative stress could affect the amyloid-beta phagocytic potential of macrophages and hence by alleviating oxidative stress using curcumin, an anti-oxidant could enhance the amyloid-beta phagocytic efficacy of macrophages of patients with AD and MCI, although the responsiveness to curcumin might depends on the presence or absence of APOEε4 allele. Oxidative stress contributes significantly to decreased phagocytosis of Aß by macrophages. Moreover, the phagocytic inefficiency of macrophages was correlated to the presence of ApoEε4 allele. This study also found that the Aß-phagocytic potential of macrophage gets significantly enhanced in curcumin-treated patient-derived macrophages.

The effect of polypharmacy on prefrontal cortex activation during single and dual task walking in community dwelling older adults.

INTRODUCTION: Polypharmacy, defined as the use of 5 or more medications is associated with multiple adverse outcomes in older adults, including falls and slow gait velocity. However, the relationship between polypharmacy and cortical control of locomotion has not been reported. The purpose of this study was to examine the relationship between polypharmacy and activation patterns in the prefrontal cortex (PFC), a brain region involved in higher order control of locomotion during attention-demanding conditions. METHODS: Using Functional Near Infrared Spectroscopy (fNIRS) to quantify PFC oxygenated hemoglobin (HbO2) levels, we performed a cross sectional analysis of 325 community dwelling adults age ≥65 years, and examined HbO2 levels during single tasks (Single-Task-Walk (STW), (talking, cognitive interference (Alpha)) and Dual-Task Walk (DTW)). RESULTS: The prevalence of polypharmacy was 33% (n = 104) amongst the 325 participants (mean age 76.4 ± 6.7 years, 56% women). Among the 221 participants with no polypharmacy there was an increase in HbO2 levels from STW to DTW (estimate = -0.625; p = <0.001) and from Alpha to DTW (estimate=-0.079; p = 0.031). Polypharmacy status, however, moderated the change in HbO2 levels comparing the two single tasks to the dual-task walking condition. Specifically, the presence of polypharmacy was associated with an attenuated increase in HbO2 levels from STW to DTW (estimate = 0.149; p = 0.027) and with a decline in HbO2 levels from Alpha to DTW (estimate = 0.169; p = 0.009) after adjustments for potential confounders including medical comorbidities and the use of high-risk medications. CONCLUSION: The results of this study further support the need for clinicians to reduce polypharmacy in older adults, given its significant association with the PFC hemodynamic response during attention-demanding locomotion.

Picture-Based Memory Impairment Screen: Effective Cognitive Screen in Ethnically Diverse Populations.

OBJECTIVES: To describe the psychometric properties of the Picture-based Memory Impairment Screen (PMIS) in a multidisciplinary memory disorder center serving an ethnically and educationally diverse community. DESIGN: Cross-sectional cohort study. SETTING: Montefiore Center for Aging Brain (CAB) PARTICIPANTS: Individuals with cognitive complaints (N=405; average age 76±10, 66% female). MEASUREMENTS: A geriatrician or neurologist administered the PMIS, and a neuropsychologist administered the Blessed Information, Memory, and Concentration (BIMC) test and determined whether participants had dementia, mild cognitive impairment (MCI), or subjective cognitive complaints (SCC). RESULTS: Mean PMIS scores were 4.0±2.6 in participants with dementia (n=194), 6.8±1.5 in those with MCI (n= 155), and 7.0±1.8 in those with SCC (n= 56) (p<.001). PMIS scores showed similar significant linear trends when analyzed according to ethnicity, education, sex, and language. The PMIS was negatively correlated with BIMC score (p<.001). The PMIS had positive predictive value of 77%, negative predictive value of 73%, sensitivity of 68%, and specificity of 81% to detect all-cause dementia in this population of individuals with cognitive complaints. CONCLUSION: The PMIS is a quick, valid screening tool to identify cognitive impairment in individuals with cognitive complaints that accounts for cultural and educational differences.

Effect of Exceptional Parental Longevity and Lifestyle Factors on Prevalence of Cardiovascular Disease in Offspring.

Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence of cardiovascular disease (CVD), but the role of lifestyle factors in this unique cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD independent of lifestyle factors. Prevalence of CVD and CVD risk factors was assessed in a population of community-dwelling Ashkenazi Jewish adults aged 65 to 94 years. Participants included OPEL (n = 395), defined as having at least 1 parent living past the age of 95 years, and offspring of parents with usual survival (OPUS, n = 450), defined as having neither parent survive to 95 years. Medical and lifestyle information was obtained using standardized questionnaires. Socioeconomic status was defined based on validated classification scores. Dietary intake was evaluated with the Block Brief Food Frequency Questionnaire (2000) in a subgroup of the study population (n = 234). Our study found no significant differences in the prevalence of obesity, smoking, alcohol use, physical activity, social strata scores, and dietary intake between the 2 groups. After adjustment for age and gender, the OPEL demonstrated 29% lower odds of having hypertension (95% confidence interval [CI] 0.53 to 0.95), 65% lower odds of having had a stroke (95% CI 0.14 to 0.88), and 35% lower odds of having CVD (95% CI 0.43 to 0.98), compared with OPUS. In conclusion, exceptional parental longevity is associated with lower prevalence of CVD independent of lifestyle, socioeconomic status, and nutrition, thus highlighting the potential role of genetics in disease-free survival among individuals with exceptional parental longevity.

Polypharmacy and Gait Performance in Community-dwelling Older Adults.

OBJECTIVES: To examine the relationship between polypharmacy and gait performance during simple (normal walk (NW)) and complex (walking while talking (WWT)) locomotion. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Community-dwelling older adults (N = 482). MEASUREMENTS: Polypharmacy, defined as use of five or more medications and a cohort-specific alternate definition of eight or more medications, was examined. Velocity (cm/s) measured quantitatively during NW and WWT conditions. RESULTS: The 164 participants (34%) with polypharmacy of five or more medications were older (77.0 ± 6.6 vs 76.0 ± 6.4) and more likely to have hypertension, congestive heart failure, diabetes mellitus, myocardial infarction, and higher body mass index (BMI) and to have fallen within the last year than the remaining 318 without polypharmacy and walked 6 cm/s slower (P = .004) during NW and 4 cm/s slower during WWT (P = .07), adjusting for age, sex, and education. Group differences were not statistically significant after adjusting for comorbidities. Prevalence of polypharmacy of eight or more medications was 10%. This group walked 11 cm/s slower during NW (P < .001) and 8.6 cm/s slower during WWT (P = .01) than those without polypharmacy, adjusted for age, sex, and education. Participants taking eight or more medications had slower NW (8.5 cm/s; P = .01), and WWT (6.9 cm/s; P = .07), compared to those without polypharmacy, adjusting for comorbidities. Adjustments for BMI, high-risk drugs, falls, and comorbidities yielded slower NW (9.4 cm/s, P = .005) and WWT (7.9 cm/s, P = .04 among those with polypharmacy compared to those without polypharmacy). CONCLUSION: These results suggest an association between polypharmacy and locomotion that medical comorbidities only partly explained.

Biology of Falls: Preliminary Cohort Study Suggesting a Possible Role for Oxidative Stress.

BACKGROUND: Biological underpinnings of falls in older adults are not well established. OBJECTIVES: To examine the validity of selected oxidative stress and inflammatory biomarkers for predicting incident falls in community-dwelling older adults. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 266 non-demented and ambulatory community-dwelling older adults (mean age 78 years, 55% women). MEASUREMENTS: Oxidative stress (malondialdehyde) and inflammatory (interleukin-6 [IL-6]) biomarkers were selected based on associations with fall risk factors, and values were log-transformed to account for non-normal distributions. RESULTS: Over a mean follow-up of 20.5 ± 10.1 months, 119 participants fell. In Cox proportional hazards models, each one standard deviation increase in baseline log-malondialdehyde levels predicted incident falls (Hazard ratio (HR) adjusted for age, gender, education, comorbidity count, medications, log-IL-6 levels, prior falls, depressive symptoms, cognitive status, gait velocity, and balance 1.53, 95% CI 1.11-2.16). Log-IL-6 levels were not associated with falls. Participants in the highest log-malondialdehyde quartile at baseline had increased risk for incident falls than those in the lowest quartile (HR 2.47, 95% CI 1.41-4.34). CONCLUSION: Oxidative stress predicted falls in a community-based cohort, and should be further examined as a fall risk biomarker as well as a potential target to prevent falls.

Cognitive Reserve and Postoperative Delirium in Older Adults.

OBJECTIVES: To examine the role of cognitive reserve in reducing delirium incidence and severity in older adults undergoing surgery. DESIGN: Prospective cohort study. SETTING: Hospital. PARTICIPANTS: Older adults (mean age 71.2, 65% women) undergoing elective orthopedic surgery (N = 142). MEASUREMENTS: Incidence (Confusion Assessment Method) and severity (Memorial Delirium Assessment Scale) of postoperative delirium were the primary outcomes. Predictors included early- (literacy) and late-life (cognitive activities) proxies for cognitive reserve. RESULTS: Forty-five participants (32%) developed delirium. Greater participation in cognitive activity was associated with lower incidence (odds ratio = 0.92 corresponding to increase of 1 activity per week, 95% confidence interval (CI) = 0.86-0.98, P = .006) and severity (B = -0.06, 95% CI = -0.11 to -0.01, P = .02) of delirium after adjustment for age, sex, medical illnesses, and baseline cognition. Greater literacy was not associated with lower delirium incidence or severity. Of individual leisure activities, reading books, using electronic mail, singing, and computer games were associated with lower dementia incidence and severity. CONCLUSION: Greater late-life cognitive reserve was associated with lower delirium incidence and severity in older adults undergoing surgery. Interventions to enhance cognitive reserve by initiating or increasing participation in cognitive activities may be explored as a delirium prophylaxis strategy.

Motoric Cognitive Risk Syndrome: Prevalence and Risk Factors in Japanese Seniors.

OBJECTIVES: Motoric cognitive syndrome (MCR), a newly described predementia syndrome characterized by cognitive complaints and slow gait, is associated with increased risk of developing dementia. Due to the potential differences in health, behavioral, and lifestyle factors between races that can influence dementia risk, it is important to examine risk factors for MCR in different countries. This study aimed to report the prevalence as well as modifiable factors associated with MCR in Japanese community-dwelling older adults. DESIGN: A cross-sectional design. SETTING: General community. PARTICIPANTS: A total of 9683 older adults (52% women, mean age: 73.6 years) participating in the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes. MEASUREMENTS: Participants were screened for presence of MCR at baseline. The association of selected modifiable risk factors (medical illness, depressive symptoms, and falls) and lifestyle variables (obesity, physical inactivity, smoking, and alcohol consumption) with MCR was examined using multivariate logistic regression analysis. RESULTS: At cross-section, 619 participants met criteria for MCR, with an overall prevalence 6.4% (95% CI 5.9-6.9). A higher prevalence of MCR was seen with advancing age (P < .001), but there were no sex differences. Diabetes (adjusted odds ratio [OR] 1.47, P = .001), depressive symptoms (OR 3.57, P < .001), and falls (OR 1.45, P < .001) were associated with increased risk of MCR. Among the lifestyle factors, obesity (OR 1.26, P = .018) and physical inactivity (OR 1.57, P < .001) were associated with increased risk of MCR. CONCLUSION: MCR is common in the elderly Japanese population. The potentially modifiable risk and lifestyle factors identified for MCR should be further studied to develop interventions.

Brain health: the importance of recognizing cognitive impairment: an IAGG consensus conference.

Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline.

Incidence of Alzheimer's disease in India: a 10 years follow-up study.

OBJECTIVE: To determine overall and age-specific incidence rates of Alzheimer's disease (AD) in a southern Indian province, Kerala. MATERIALS AND METHODS: A 10-year (2001-2011) prospective epidemiologic study of community residing subjects aged ≥55 years at enrollment. The catchment area included four urban and semi-urban regions of Trivandrum city in Kerala, India, was selected to provide a range of demographic and socioeconomic representation. Cognitive and functional ability screening were done at baseline and 24-month follow-up assessments. Consensus diagnostic procedures were done using the Diagnostic and Statistical Manual of Mental Disorders, 4 th edition (DSM-IV), and the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for the diagnosis of dementia and AD. RESULTS: Among the 1066 eligible participants who were cognitively normal at baseline, 104 developed dementia (98 with AD) over a follow-up period of 8.1 years. The incidence rates per 1000 person-years for AD was 11.67 (95% CI: 10.9-12.4) for those aged ≥55 years and higher for those aged ≥65 years (15.54, 95% CI: 14.6-16.5). In those aged ≥65 years, the world age standardized incidence rate was 21.61 per 100,000, and standardized against the age distribution for the year 2000 U.S. Census, the age-adjusted incidence rate was 9.19 (95% CI: 9.03-9.35) per 1000 person-years. Incidence rate of AD increased significantly and proportionately with increasing age. CONCLUSION: These are the first AD incidence rates to be reported from southern India. The incidence rates appear to be much higher than that reported from rural north India, comparable with that reported from China, and marginally lower than that reported from the western world.

Inflammatory markers and gait speed decline in older adults.

BACKGROUND: Increased inflammatory activity and gait speed decline are common with aging, but the association between the two is not well established. The objective of this study was to determine the influence of inflammatory markers, interleukin-6 (IL-6), and tumor necrosis factor alpha, on gait speed performance and decline in older adults. METHODS: We conducted cross-sectional and longitudinal analyses of 333 adults aged 70 and older (61% women) with gait and biomarker assessments identified from participants in the Einstein Aging Study, a community-based aging study. Gait velocity measured at baseline and annual follow-up visits (median follow-up 2.3 years) was the main outcome. RESULTS: At baseline, higher interleukin-6 levels were associated with slower gait velocity (estimate -4.90 cm/s, p = .008). Adjusted for age, gender, education, and medical illnesses, a one-unit increase in baseline log IL-6 levels was associated with a 0.98 cm/s faster gait speed decline per year (p = .002). The results remained significant after adjustments for additional potential confounders such as physical activity levels, body mass index, and medications. Participants in the highest IL-6 quartile had a 1.75 cm/s/year faster decline in gait velocity compared with those in the lowest quartile (p = .002). Tumor necrosis factor alpha was not associated with gait velocity at cross-section or with gait speed decline. CONCLUSIONS: IL-6 levels are associated with gait performance in community residing seniors and predicts risk of gait speed decline in aging.

Walking speed and risk of incident ischemic stroke among postmenopausal women.

BACKGROUND AND PURPOSE: Walking speed is a simple, reliable, and valid measure of functional status that has been shown to be strongly correlated with age-related outcomes and may be an indicator of subclinical cerebrovascular disease. However, few studies have investigated the association of walking speed with risk of incident ischemic stroke. METHODS: The present analyses included 13,048 postmenopausal women (mean age 65 years) from the Women's Health Initiative free of stroke at baseline, 264 of whom had incident ischemic strokes on follow-up. Cox proportional hazards regression was used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the relationship between performance on a timed walk and risk of incident ischemic stroke. Multivariate adjustment included age, race/ethnicity, body mass index, waist-hip ratio, depression, arthritis, hypertension, smoking, systolic blood pressure, treated diabetes, hormone use, NSAID use, aspirin use, self-reported general health, and history of coronary heart disease. RESULTS: Slower walking speed was a significant predictor of incident ischemic stroke. After multivariate adjustment, the hazard for incident ischemic stroke was increased for the slowest walking speed tertile compared to the fastest walking speed tertile (HR=1.69, 95% CI: 1.21, 2.36). Additional adjustment for other physical function variables (grip strength and chair stands) did not change the association significantly. CONCLUSIONS: Slow walking speed was found to be a strong predictor of increased risk of incident ischemic stroke among postmenopausal women independent of other established risk factors for stroke.

Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging.

Although evidence suggests that extensive cortical beta-amyloid (Abeta) deposition is essential in Alzheimer disease (AD), it is also detected in nondemented elderly individuals with pathologic aging (PA). Given evidence that neutral endopeptidase (NEP) or neprilysin, a key enzyme for clearance of Abeta, is decreased in AD, the goal of the present study was to determine if NEP was also decreased in PA. We measured NEP immunoreactivity in frontal cortex of 12 AD and six PA cases and compared this with 10 normal (N) elderly individuals. None had any significant other pathology, and they were similar with respect to age, sex, and postmortem delay. In addition, Abeta1-40 and Abeta1-42 were measured by enzyme-linked immunosorbent assay (ELISA), whereas tau, synaptophysin, and alpha-synuclein were measured on Western blots. The AD cases had more neuritic plaques, neurofibrillary tangles, higher Braak stage, and more tau immunoreactivity in frontal cortex than both PA and N. In contrast, both PA and AD had more senile plaques and Abeta1-42 than N. NEP immunoreactivity was decreased in AD but not in PA. The decrease was unlikely the result of neuronal or synaptic loss because NEP immunoreactivity in frontotemporal degeneration with comparable degrees of synaptic loss as the AD cases was not different from control subjects. Although NEP enzyme activity was decreased in approximately half the AD cases, on average, it was not decreased compared with N or PA. The results add further evidence that PA is distinct from AD and indicate that decreased Abeta degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD.

Screening for dementia by telephone using the memory impairment screen.

OBJECTIVES: : To develop and assess telephone-based screening tests for dementia, especially Alzheimer's disease (AD). DESIGN: : A cross-sectional validation study nested within a longitudinal study of aging and dementia. SETTING: : The Einstein Aging Study of the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: : Three hundred elderly community volunteers living in Bronx County, 27 of whom were diagnosed with dementia based on in-person clinical evaluation. Of the 27 individuals with dementia, 18 had AD. MEASUREMENTS: : A telephone battery was administered that included the Memory Impairment Screen by telephone (MIS-T, a test of semantic memory), the Category Fluency Test (CF-T), and the Telephone Instrument for Cognitive Status (TICS). An in-person evaluation then followed that included a neurological examination, a neuropsychological battery, demographics, and medical history. RESULTS: : The telephone battery was well accepted. The MIS-T required 4 minutes; the CF-T, 3 minutes; and the TICS, 10 minutes. The MIS-T had excellent sensitivity and specificity when compared with the CF-T and the TICS. Using cutscores on all three tests that provide a sensitivity of 78%, specificity was significantly higher for the MIS-T (93%) than for the CF-T (78%, P<.05) or the TICS (80%, P<.05). Combining the MIS-T and CF-T improved discriminative validity but increased screening time and the complexity of scoring. Normative data for the MIS-T, the CF-T, and the TICS for use in settings with different base rates (prevalence) of dementia are presented in this study. CONCLUSION: : The MIS-T outperforms the CF-T and the TICS as a valid and time-efficient telephone screen for dementia. For applications that require optimal efficiency and accuracy, the MIS-T is recommended.