Gait Speed and Decline in Gait Speed as Predictors of Incident Dementia.

BACKGROUND: Slow gait is common in dementia, but it remains unknown whether the slowing happens many years prior to dementia onset. We therefore examined the relationship between slow baseline gait speed (GS), change in GS, and the hazard of incident dementia in a community dwelling of elderly people. METHODS: A total of 3,663 participants dementia-free at baseline (mean age, 73.5 years) were followed up for 9 years from a prospective cohort (Three-City study, France) for incident dementia (all-cause, Alzheimer's disease, vascular dementia, and other causes). GS over 6 m was assessed 4 times over the follow-up using two photoelectric cells. We used a multistate model to estimate the hazard ratio (HR) of dementia for baseline GS and tested a washout period of 4 to 7 years. The role of GS change between 65 and 85 years was examined using linear mixed models and joint models for survival and longitudinal data. RESULTS: A total of 296 participants developed dementia during the follow-up. In age/sex-adjusted models, 1-SD (0.204 m/s) lower GS was associated with an increased hazard of dementia (HR = 1.59, 95% confidence interval [CI] = 1.39, 1.81, p < .001), with associations evident when gait assessments were taken from 4 years (HR = 1.46; CI = 1.26, 1.68) and 7 years (HR=1.30; CI = 1.00, 1.70) prior to dementia onset. Independently of baseline GS, those with a steeper decline had a higher hazard of dementia (HR per 1 SD [0.007 m/s/year] decrease = 3.39 [1.37-8.43], p = .009). CONCLUSIONS: Gait is slower up to 7 years prior to clinical onset of dementia. Decline in GS is also more accelerated, suggesting strong links between cognitive and motor function in older adults.

Body mass index trajectories and functional decline in older adults: Three-City Dijon cohort study.

Obesity, whose prevalence is increasing, is associated with poor functional status at older ages. However, much of this evidence is cross-sectional with little known about longitudinal associations. We examined associations of body mass index (BMI), and change in BMI, with change in objective [walking speed (WS)] and self-reported (disability) measures of motor decline. Analyses included participants (65-85 years) from the Dijon center of the Three-City study (France) with up to five WS (N = 4007) and six disability assessments (N = 4478) over 11 years. Data were analyzed using regression models for repeated measures. Mean baseline WS was 153 cm/s. Compared to normal weight persons, obese participants at baseline walked slower and reported more disability; they also experienced 45% faster WS decline (-18.63 vs. -12.85 cm/s/10 years, P = 0.002). Participants who lost or gained weight had 47% (-18.85 cm/s/10 years, P < 0.001) and 33% (-17.08 cm/s/10 years, P = 0.002) respectively greater WS decline than participants in the normal BMI change category. 24% of participants reported disability at least once during the follow-up, those who lost or gained weight had a 1.63 and 1.34 respectively higher odds of disability than participants in the normal BMI change category (P = 0.001). Associations remained after adjustment for covariates. In conclusion, obesity is associated with worse motor performances, a higher risk of disability, and faster motor decline. Our results underline the interest of repeated BMI and motor assessments to identify those at higher risk of disability.

Lipid-lowering drugs associated with slower motor decline in the elderly adults.

BACKGROUND: Vascular risk factors contribute to motor decline in the elderly persons. We investigated the relationship between lipid-lowering drugs (LLDs) use and decline in walking speed (WS) in older adults. METHODS: Data on 4,009 community-dwelling men and women, aged ≥65 years at baseline, are drawn from the Dijon (France) center of the Three-City study. "Fast" WS was assessed over 6 m at baseline and at 4, 6, 8, and 10 years of follow-up. Mixed linear models were used to determine the relationship between LLDs and change in WS over the follow-up. RESULTS: At baseline, 1,295 (32%) participants used LLDs (statins, n = 643; fibrates, n = 652); mean fast WS was 152.9cm/s and not significantly different between LLDs users and nonusers. In models adjusted for age, sex, cholesterol level, and other covariates, WS decline was 25% slower in LLDs users (difference with nonusers: 0.58cm/s/y, 95% CI: 0.30, 0.86; p < .001). Both fibrates and statins were associated with slower decline, but only the effect of statins was robust in analyses that took missing values into account. The beneficial effect was more pronounced in those on LLDs continuously over the follow-up. CONCLUSION: Fast WS declined less in those on LLDs, suggesting that the effect of LLDs, statins in particular, extend beyond that on cardiovascular disease in the elderly persons. However, these effects were modest and their clinical relevance is unclear.

Change in fast walking speed preceding death: results from a prospective longitudinal cohort study.

BACKGROUND: Walking speed (WS) predicts mortality. However, it is unclear if decline in WS increases prior to death. We examined whether (a) WS declined faster in persons who died during the follow-up compared with those who remained alive and (b) adding change in WS to a model including age, sex, and baseline WS improved prediction of mortality. METHODS: Data are from 4,016 participants of the Dijon center of the Three-City study (France), aged 65-85 years. Fast WS (FWS) was measured up to five times over a 12-year period. Mortality was ascertained until 2012. RESULTS: Linear mixed models using a backward time scale showed that FWS declined faster in 908 participants who died during the follow-up (annual change = -0.031 m/s) than in those who survived (-0.021 m/s), corresponding to a difference of -0.009 (95% confidence interval = -0.013 to -0.005) m/s. Compared with "normal" change in FWS (annual change ≥-0.04 m/s), "substantial" decline (<-0.08 m/s) was associated with a 1.4-fold greater risk of mortality (hazards ratio = 1.40, confidence interval = 1.02-1.92) and small decline (-0.08 to -0.04 m/s) with a 1.2-fold greater risk (hazards ratio = 1.18, confidence interval = 0.89-1.57). The net reclassification index when adding these categories of change in FWS to the model adjusted for age, sex, and baseline FWS was 19.0% (0.6, 36.8%). CONCLUSION: Participants who died during the follow-up had a steeper decline in FWS than the others. Both baseline FWS and FWS decline predict mortality.

Motor function in the elderly: evidence for the reserve hypothesis.

OBJECTIVE: The reserve hypothesis accounts for the lack of direct relationship between brain pathology and its clinical manifestations. Research has mostly focused on cognition; our objective is to examine whether the reserve hypothesis applies to motor function. We investigated whether education, a marker of reserve, modifies the association between white matter lesions (WMLs), a marker of vascular brain damage, and maximum walking speed (WS), an objective measure of motor function. We also examined the cross-sectional and longitudinal association between education and WS. METHODS: Data are from 4,010 participants aged 65-85 years in the longitudinal Three-City-Dijon Study with up to 4 WS measures over 10 years. We examined the interaction between education and WMLs for baseline WS. We studied the association between education and repeated WS measures using linear mixed models, and the role of covariates in explaining the education-WS association. RESULTS: Education was strongly associated with baseline WS; the difference in mean WS between the high and low education groups (0.145 m/s, 95% confidence interval = 0.125-0.165) was equivalent to 7.4 years of age. WMLs were associated with slow WS only in the low education group (p interaction = 0.026). WS declined significantly over time (-0.194 m/s/10 years, 95% confidence interval = -0.206, -0.182), but education did not influence rate of decline. Anthropometric characteristics, parental education, general health, and cognition had the strongest role in explaining the baseline education-WS association. CONCLUSIONS: Participants with more education were less susceptible to WMLs' effect on motor function. Higher education was associated with better motor performances but not with motor decline. These results are consistent with the passive reserve hypothesis.

MRI atrophy of the caudate nucleus and slower walking speed in the elderly.

Cerebral white matter lesions are associated with poorer motor performances in the elderly, but the role of gray matter atrophy remains largely unknown. We investigated the cross-sectional relation between brain regional gray matter volumes and walking speed over 6m in the 3C-Dijon study, a large population-based study of community-dwelling persons aged 65 years and over (N=1623). Regional gray matter volumes were obtained using an automated anatomical labeling parcellation method. Multivariable analyses were performed using a semi-Bayes approach. After adjustment for potential confounders, persons who walked slower had a smaller volume of basal ganglia (regression coefficient [ß]=0.054, standard error [SE]=0.028, p=0.05). In more detailed analyses, the volume of the caudate nucleus had a preponderant role on this association (ß=0.049, SE=0.019, p=0.009), and walking speed decreased progressively with the volume of the caudate nucleus (p for linear trend<0.001). These results underline the role of gray matter subcortical structures, in particular of the caudate nucleus, in the age-related decline of motor performances among community-dwelling elderly subjects.

Engagement in leisure activities and benzodiazepine use in a French community-dwelling elderly population.

OBJECTIVE: The prevalence of benzodiazepine use among community-dwelling older persons varies between 10% and 30%. The aim of this study was to explore the association between leisure activities and the use of benzodiazepine among older persons living at home. METHODS: The study population included 4848 persons aged 65 years and over living in either of two French cities. Information was collected from a questionnaire administered to the respondents by trained psychologists during face-to-face interviews at home and from a self-administered questionnaire. Baseline examination included socio-demographic characteristics, drug use and leisure activities. We classified as benzodiazepine users subjects who reported use of at least one benzodiazepine during the month preceding the interview. The association between the use of benzodiazepine and leisure activities was assessed by logistic regression adjusted on known potential confounders. RESULTS: More than 18% of participants reported use of at least one benzodiazepine. The adjusted odds ratio (OR) of benzodiazepine use associated with no or lower participation versus participation in the following activities were as follows: OR = 1.31 (95% confidence interval (CI): 1.09 to 1.58) for mental activity; OR = 1.50 (CI: 1.12 to 2.03) for physical activity; OR = 1.28 (CI: 1.05 to 1.55) for productive activity and OR = 0.82 (CI: 0.69 to 0.97) for recreational activity. CONCLUSION: Low engagement in stimulating activities and high engagement in sedentary activities were associated with recent benzodiazepine use.

Insomnia symptoms in older adults: associated factors and gender differences.

OBJECTIVES: the aim of this study was to examine the factors associated with insomnia in community-dwelling elderly as a function of the nature and number of insomnia symptoms (IS), e.g., difficulty with initiating sleep (DIS), difficulty with maintaining sleep (DMS), and early morning awakening (EMA). METHODS: is were assessed in a sample of 2,673 men and 3,213 women aged 65 years and older. The participants were administered standardized questionnaires regarding the frequency of IS and other sleep characteristics (snoring, nightmares, sleeping medication, and sleepiness) and various sociodemographic, behavioral and clinical variables, and measures of physical and mental health. RESULTS: more than 70% of men and women reported at least one IS, DMS being the most prevalent symptom in both men and women. Women reported more frequently two or three IS, whereas men reported more often only one IS. Multivariate regression analyses stratified by gender showed that men and women shared numerous factors associated with IS, sleeping medication, nightmares, sleepiness, chronic diseases, and depression being independently associated with two or three IS. For both sexes, age was associated with only one IS in all age categories. Loud snoring was strongly associated with increased DMS in men only. High body mass index increased the risk for DIS in men but tended to decrease it in women. In women, hormonal replacement therapy, Mediterranean diet, and caffeine and alcohol intake had a protective effect. CONCLUSION: our data suggest that women may have specific predisposition factors of multiple IS, which may involve both behavioral and hormonal factors. Identification and treatment of these risk factors may form the basis of an intervention program for reduction of IS in the elderly.

A prospective study of hormone therapy and depression in community-dwelling elderly women: the Three City Study.

BACKGROUND: The potential benefits of hormone therapy (HT) in treating depressed postmenopausal women are controversial, and data on depression (re)emergence in the context of HT discontinuation are lacking. OBJECTIVE: To determine whether HT is associated with a modified risk of new-onset depressive symptoms in elderly women. METHOD: Current depressive symptomatology was evaluated in 4,069 community-dwelling postmenopausal women aged 65 years and over who were randomly recruited from 3 French cities between 1999 and 2001. Depressive symptomatology was assessed using the Center for Epidemiologic Studies-Depression Scale at baseline and as part of the 2- and 4-year follow-up. RESULTS: Over the follow-up period, multivariate logistic regression analyses adjusted for sociodemographic variables, measures of physical health, and cognitive impairment failed to find a significant association between HT at baseline and the incidence of depressive symptoms. However further analysis indicated an increased risk of incident depressive symptoms for women using transdermal estradiol treatment combined with synthetic progestin specifically (odds ratio [OR] = 1.59; 95% CI, 1.01-2.50; P = .046). In addition, while women taking HT continuously over the 4-year follow-up did not show an increased risk of depressive symptoms, women who stopped their treatment early after study inclusion, had a significantly higher risk (OR = 2.63; 95% CI, 1.52-4.55; P = .0005). CONCLUSIONS: Hormone therapy was not associated with a protective effect against the emergence of depressive symptoms in elderly postmenopausal women. However, discontinuing treatment could increase the risk of depressive symptoms. Data on the appropriate management of depression in the context of HT discontinuation among postmenopausal women require further investigation.

Hypertension and lower walking speed in the elderly: the Three-City study.

OBJECTIVE: The brain is one of the main targets of hypertension. However, little is known about the relation between hypertension and motor performances. We studied the association between hypertension and walking speed in a cohort of elderly people. METHODS: Analyses are based on participants (65-85 years) from the Dijon (France) center of the Three-City study (n = 3604), followed every 2 years. Persistent hypertension was defined by the use of antihypertensive drugs at baseline or at first follow-up, or by high blood pressure (> or =140/90 mmHg) at baseline and first follow-up. Walking speed was measured over 6 m, at baseline and fourth follow-up (n = 1774) after a mean (SD) duration of 7.0 (0.5) years. Brain MRI was performed in 1590 participants. Generalized linear models were used to assess the relation between hypertension and baseline walking speed or walking speed change. RESULTS: At baseline, mean (SD) walking speed (m/s) was lower in hypertensive patients [1.51 (0.31)] than in nonhypertensive individuals [1.59 (0.30), P < 0.001]. During follow-up, hypertensive patients had a higher mean annual decline in walking speed [cm/s per year; 2.30 (3.4)] than nonhypertensive individuals [1.87 (3.3), P = 0.004]. The number of antihypertensive drugs was associated with lower walking speed at baseline and higher walking speed decline. Adjustment for MRI white matter abnormalities attenuated these relations. CONCLUSION: Persistent hypertension was associated with both lower walking speed and higher decline in walking speed in the elderly. These results may be partly explained by white matter abnormalities and support the hypothesis of a contribution of vascular risk factors to motor dysfunction.

Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study.

OBJECTIVE: To study the relation between low walking speed and the risk of death in older people, both overall and with regard to the main causes of death. DESIGN: Prospective cohort study. SETTING: Dijon centre (France) of the Three-City study. PARTICIPANTS: 3208 men and women aged >or=65 living in the community, recruited from 1999 to 2001, and followed for an average of 5.1 years. MAIN OUTCOME MEASURES: Mortality, overall and according to the main causes of death, by thirds of baseline walking speed (measured at maximum speed over six metres), adjusted for several potential confounders; Kaplan-Meier survival curves by thirds of baseline walking speed. Vital status during follow-up. Causes of death. Results During 16 414 person years of follow-up, 209 participants died (99 from cancer, 59 from cardiovascular disease, 51 from other causes). Participants in the lowest third of baseline walking speed had an increased risk of death (hazard ratio 1.44, 95% confidence interval 1.03 to 1.99) compared with the upper thirds. Analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death (2.92, 1.46 to 5.84) compared with participants who walked faster. There was no relation with cancer mortality (1.03, 0.65 to 1.70). In stratified analyses, cardiovascular mortality was increased across various strata defined by sex, median age, median body mass index (BMI), and level of physical activity. Conclusion Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality.

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.

The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P < 10(-5)) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 x 10(-9) for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.

Inappropriate medication use and risk of falls--a prospective study in a large community-dwelling elderly cohort.

BACKGROUND: Explicit criteria for determining potentially inappropriate medication consumption in elderly were elaborated by Beers et al. These lists have been used worldwide to evaluate medical prescriptions but there is little epidemiologic evidence demonstrating negative consequences of inappropriate medication use. It has been reported that some drugs could increase the risk of falls, which are a frequent and serious problem in elderly population. We aimed to evaluate the association between the use of potentially inappropriate medications and the risk of falls. METHODS: The 3C Study is a multicentre prospective cohort study conducted in France with 4 years of follow-up. Non-institutionalized men and women aged 65 years or over (N = 6343) were randomly selected from electoral rolls. Data on socio-demographic, medical characteristics and medication use (based on self-reports and data from the national healthcare insurance) were collected. Use of inappropriate medication for elderly was defined from established criteria. Data about falls were collected at the two follow-up examinations (2 years and 4 years after baseline). The association between the exposure to inappropriate medications and the risk of falls was evaluated using multivariate models (Cox model and logistic regression). RESULTS: 32% of subjects reported inappropriate medication use at baseline and 29% at least two of the three examinations; 22% had fallen 2 times or more during follow-up. Overall, inappropriate medication users had an increased risk of falling. This increase was mainly due to the use of long-acting benzodiazepines (adjusted odds ratio (OR) = 1.4, 95% confidence interval: [1.1-1.8], in both occasional and regular users), other inappropriate psychotropics (adjusted OR = 1.7 [1.7-2.7] in regular users), or medication with anticholinergic properties (adjusted OR = 1.6 [1.2-2.1] in regular users). Neither occasional, nor regular use of short- or intermediate-acting benzodiazepines was associated with an increased risk of falling. Further analysis in long-acting benzodiazepines users did not show any dose-effect relation between the number of prescriptions filled over a 3-year period and the risk of falling. CONCLUSION: Our study showed that use of inappropriate medications was associated with an increased risk of falling in elderly persons. This increase was mainly due to long-acting benzodiazepines and other inappropriate psychotropics, and to medications with anticholinergic properties.

A cross-sectional and longitudinal study of the relationship between walking speed and cognitive function in community-dwelling elderly people.

BACKGROUND: Previous reports have shown links between cognitive function and physical performance in the elderly people, but it is unclear whether some specific cognitive domains are more strongly associated with measures of physical function such as walking speed. We investigated cross-sectional and longitudinal relationships between performance in five cognitive tests and walking speed among community-dwelling elderly people in the Dijon center (France) of the Three-City Study. METHODS: At baseline, 3,769 participants aged 65-85 years had measurements of 6-m walking speed, global cognition (Mini-Mental State Examination), verbal fluency (Isaacs Set Test [IST]), psychomotor speed (Trail Making Test part A [TMT-A]), executive function (TMT part B), and memory (Benton Visual Retention Test). After a mean follow-up of 7 years, walking speed was again measured in 1,732 of these participants. RESULTS: In cross-sectional analyses, slower maximum walking speed (MWS) at baseline was significantly associated with poorer performance in each cognitive test. The association was stronger with TMT-A (beta [SE] = -.127 [0.014], p < .0001) and IST (beta [SE] = .120 [0.014], p < .0001) than with the other tests. Only TMT-A (beta [SE] = -.053 [0.021], p = .01) and IST (beta [SE] = .063 [0.022], p = .004) were associated with the degree of MWS decline over time. CONCLUSIONS: This study shows both cross-sectional and longitudinal associations between cognition and walking speed among community-dwelling elderly people. Poorer verbal fluency and slower psychomotor speed were more specifically associated with slower baseline MWS and with a stronger decline in MWS over time.

White matter lesions volume and motor performances in the elderly.

OBJECTIVES: To investigate the cross-sectional and longitudinal associations between performance-based measures of motor function and volume of white matter lesions (WMLs), and to examine the influence of the localization of these lesions. METHODS: At baseline, motor performances (maximum walking speed, Tinetti gait and balance subscales) were assessed in 1,702 subjects aged 80 years or younger from the Dijon (France), France center of the Three-City study. Volumes of WMLs lesions (total, periventricular, deep) were measured using an automated method of tissue segmentation and quantification of lesion size. At 8-year follow-up, walking speed was evaluated in 1,086 subjects. RESULTS: At baseline, mean and 95% confidence interval (CI) walking speed was lower in subjects with total volumes of WMLs >or=90th percentile (1.50 [1.45-1.55] m/s) than in subjects with lower volumes (1.56 [1.55-1.58] m/s; p = 0.004). Baseline total volumes of WMLs above the 90th percentile predicted walking speed decline during follow-up (odds ratio [95% CI] for having the greatest walking speed decline = 2.3 [1.3-4.1], p = 0.006). Moreover, high volumes of periventricular but not deep WMLs were associated with slower walking speed at baseline (p = 0.005) and over time (p = 0.001), and with lower Tinetti gait subscore (p = 0.02). INTERPRETATION: Our study shows a cross-sectional and longitudinal association between high total volumes of WMLs, in particular volumes above the 90th percentile, and impaired mobility. These associations were independent of several confounders, including cognition, and were mainly accounted for by volumes of periventricular WMLs. These findings support the hypothesis of a vascular contribution to motor decline in the elderly.

Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study.

OBJECTIVES: To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes. DESIGN: Four-year longitudinal study. SETTING: The French Three-City Study. PARTICIPANTS: Six thousand thirty community-dwelling persons aged 65 to 95. MEASUREMENTS: Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Subjects meeting one or two criteria were prefrail and those meeting none as nonfrail. The lowest quartile in the Mini-Mental State Examination (MMSE) and the Isaacs Set Test (IST) was used to identify subjects with cognitive impairment. The predictive validity of frailty for incident disability, hospitalization, dementia, and death was calculated first for frailty subgroups and then rerun after stratification according to the presence or absence of cognitive impairment. RESULTS: Four hundred twenty-one individuals (7%) met frailty criteria. Cognitive impairment was present in 10%, 12%, and 22% of the nonfrail, prefrail, and frail subjects, respectively. Those classified as frail scored lower on the MMSE and IST than those classified as prefrail and nonfrail. After adjustment, frail persons with cognitive impairment were significantly more likely to develop disability in activities of daily living (ADLs) and instrumental ADLs over the following 4 years. The risk of incident mobility disability and hospitalization was marginally greater. Incident dementia was greater in the groups with cognitive impairment irrespective of their frailty status. Conversely, frailty was not a significant predictor of mortality. CONCLUSION: Cognitive impairment improves the predictive validity of the operational definition of frailty, because it increases the risk of adverse health outcomes in this particular subgroup of the elderly population.

N-acetylaspartate/creatine and choline/creatine ratios in the thalami, insular cortex and white matter as markers of hypertension and cognitive impairment in the elderly.

Our objective was to investigate the influence of hypertension on N-acetylaspartate (NAA) and choline (Cho) ratios in brain tissues in a community-dwelling elderly population. Brain flexibility was also evaluated with regard to the same metabolite ratios. Proton magnetic resonance spectroscopy (MRS) and the Trail Making Test (TMT) were performed in 80 subjects (75.7+/-4 years old) from the Three-City Study. Fifty-eight participants had hypertension. The NAA/creatine (Cr) and Cho/Cr ratios were obtained in the insular cortex, the thalami and the deep periventricular white matter. In addition, the B-A score of the TMT was evaluated. Uni- and multi-variate analyses were performed in order to examine the relationships among these data. In the insula and the thalami of the hypertensive group, NAA/Cr ratios were significantly lower (1.39+/-0.23 and 1.52+/-0.23, respectively; p=0.01) than those in the normotensive control group (1.52+/-0.25 and 1.70+/-0.19, respectively; p<0.0001), whereas no such reduction was observed in the periventricular white matter of older hypertensive brains. Moreover, the NAA or Cho ratios were significantly correlated with the TMT B-A scores at the level of the thalami, insula and periventricular white matter. These statistical results were confirmed by the multivariate analysis. In an elderly population, hypertension leads to a reduction in NAA/Cr ratios in the insula and the thalami, possibly due to a decrease in blood flow through small perforating and cortical arteries. The TMT B-A test appears to be relevant not only for the frontal areas but also for more remote areas such as the thalami, the insula and the deep periventricular white matter.

Brain flexibility and balance and gait performances mark morphological and metabolic abnormalities in the elderly.

Although previous studies have found that cerebral white matter hyperintensities are associated with balance-gait disorders, no proton magnetic resonance spectroscopy data at the plane of the basal ganglia have been published. We investigated a possible relationship between balance performance and brain metabolite ratios or structural MRI measurements. We also included neuropsychological tests to determine whether such tests are related to structural or metabolic findings. All 80 participants were taken from the cohort of the Three-City study (Dijon-Bordeaux-Montpellier, France). The ratios of N-acetyl-aspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) were calculated in the basal ganglia, thalami and insular cortex. We used univariate regression to identify which variables predicted changes in NAA/Cr and Cho/Cr, and completed the analysis with a multiple linear or logistic regression. After the multivariate analysis including hypertension, age, balance-gait, sex, white matter lesions, brain atrophy and body mass index, only balance-gait performance remained statistically significant for NAA/Cr (p=0.01) and for deep white-matter lesions (p=0.02). The Trail-Making Test is independently associated with brain atrophy and periventricular white-matter hyperintensities. Neuronal and axonal integrity at the plane of the basal ganglia is associated with balance and gait in the elderly, whereas brain flexibility is associated with structural MRI brain abnormalities.

Frailty among community-dwelling elderly people in France: the three-city study.

BACKGROUND: To better understand the contribution of frailty to health-related outcomes in elderly persons, it seems valuable to explore data from cohort studies across the world in an attempt to establish a comprehensive definition. The purpose of this report is to show the characteristics of frailty and observe its prognosis in a large sample of French community-dwelling elderly persons. METHODS: We used data from 6078 persons 65 years old or older participating in the Three-City Study (3C). Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low activity. Principal outcomes were incident disability, hospitalization, and death. Multiple covariates were used to test the predictive validity of frailty on these outcomes. RESULTS: Four hundred twenty-six individuals (7%) met frailty criteria. Participants classified as frail were significantly older, more likely to be female, and less educated and reported more chronic diseases, lower income, and poorer self-reported health status in comparison to nonfrail participants. In multivariate analysis, frailty was significantly associated with 4-year incidence of disability in activities of daily living (ADL) and instrumental ADL. However, frailty was marginally associated with incident hospitalization and was not a statistically significant predictor of incident mobility disability or mortality adjusting for potential confounding factors. CONCLUSIONS: Frailty is not specific to a subgroup or region of the world. The construct proposed by Fried and colleagues confirms its predictive validity for adverse-health outcomes, particularly for certain components of disability, thus suggesting that it may be useful in population screening and predicting service needs.

Factors associated with morbidity during the 2003 heat wave in two population-based cohorts of elderly subjects: PAQUID and Three City.

INTRODUCTION: France was affected in early August 2003 by a heat wave with an exceptional health impact. Many studies on mortality were conducted but few data are available on morbidity. The objectives of this study were to describe the impact of the 2003 heat wave in the general population of elderly people and to determine individual factors associated with morbidity. METHODS: A cross-sectional study nested in two prospective cohorts, the PAQUID and the Three-City (3C) studies, was performed. The sample included 2295 subjects from the general population, aged 67 and over who were interviewed by a phone questionnaire to complete data available in the database of the two cohorts. Two variables assessing morbidity (felt by the person and objectively observed) were created. Relationship between morbidity and individual factors were explored in univariate analyses; then multiple logistic regressions were conducted. RESULTS: During the heat wave, 8.8% of the subjects felt a deterioration of their health, and 7.8% declared an objective morbid outcome. In the univariate analyses, many factors were associated with morbidity. After multiple adjustments, few associations were still observed but some factors were associated with a decreased risk (presence of a bathroom, dressing lighter than usually) or an increased risk (stopping usual activities, presence of chronic diseases). CONCLUSION: This study showed a non-negligible impact of the 2003 heat wave in term of felt and objective morbidity. Several individual factors were shown to be associated with morbidity and should be taken into account for the elaboration of prevention plans.