Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease

OBJECTIVES: To examine the effect of galantamine on activities of daily living (ADLs) with respect to baseline dementia severity, correlation with cognitive and global function, specific ADLs affected, and maintenance of ADL independence. DESIGN: Secondary analysis of a 5-month randomized, placebo-controlled trial. SETTING: Multiple U.S. clinical centers. PARTICIPANTS: Six hundred fifty-nine patients with mild to moderate Alzheimer's disease (AD) who completed 5 months of treatment. INTERVENTION: Galantamine at a maintenance dose of 16 or 24 mg/d. MEASUREMENTS: The AD Cooperative Study ADL Inventory (ADCS/ADL). RESULTS: Galantamine resulted in more improvement in ADCS/ADL scores than placebo regardless of baseline dementia severity, with the greatest differences occurring in patients with more severe disease. Changes in ADCS/ADL scores correlated significantly with change scores on the cognitive subscale of the AD Assessment Scale (r=-0.24). Galantamine treatment resulted in maintenance or improvement of basic and instrumental ADLs, and change from baseline to Month 5 in scores for each individual ADL item favored galantamine over placebo in three of six basic ADLs and six of 17 instrumental ADLs. CONCLUSION: Galantamine has a favorable effect on ADL performance in patients with AD, detectable after 5 months of treatment, regardless of dementia severity. The ADCS/ADL appears to better measure distinct abilities that may be relevant not only in clinical trials but also in individual patients than do cognitive assessments.     

Comparisons of cognitive deterioration rates by dementia subtype

Pathophysiological aspects of dementia and its rate of cognitive deterioration could be dependent on disease subtype, Alzheimer's dementia (AD), vascular dementia (VaD), and Parkinson's disease with dementia (PDD). 150 patients diagnosed at the Chungnam National University Hospital (87 women and 63 men) memory clinic. The participants consisted of 68 patients with AD, 23 patients with VaD, and 59 patients with PDD, who were diagnosed by the individual criteria, respectively. Cognitive screening was evaluated using the Korean version of the mini-mental state examination (MMSE). Repeated evaluations were conducted at 6-month, 1 year, and 2 years after initial baseline assessment. Rates of cognitive decline were calculated by dividing MMSE score differences by the number of months lapsed. No difference was found between the three dementia subtypes with respect to baseline MMSE scores. Cognitive decline was not obvious up to 6-month of the follow-up, but by 12-month of follow-ups was significant regardless of the dementia subtype. Furthermore, the rate of cognitive decline in the AD group was significantly faster than in the PDD or VaD groups. This study suggests that rate of cognitive deterioration in dementia is not linear over time and that dementia subtypes have different rates of cognitive deterioration.     

Comparisons of cognitive deterioration rates by dementia subtype

Pathophysiological aspects of dementia and its rate of cognitive deterioration could be dependent on disease subtype, Alzheimer's dementia (AD), vascular dementia (VaD), and Parkinson's disease with dementia (PDD). 150 patients diagnosed at the Chungnam National University Hospital (87 women and 63 men) memory clinic. The participants consisted of 68 patients with AD, 23 patients with VaD, and 59 patients with PDD, who were diagnosed by the individual criteria, respectively. Cognitive screening was evaluated using the Korean version of the mini-mental state examination (MMSE). Repeated evaluations were conducted at 6-month, 1 year, and 2 years after initial baseline assessment. Rates of cognitive decline were calculated by dividing MMSE score differences by the number of months lapsed. No difference was found between the three dementia subtypes with respect to baseline MMSE scores. Cognitive decline was not obvious up to 6-month of the follow-up, but by 12-month of follow-ups was significant regardless of the dementia subtype. Furthermore, the rate of cognitive decline in the AD group was significantly faster than in the PDD or VaD groups. This study suggests that rate of cognitive deterioration in dementia is not linear over time and that dementia subtypes have different rates of cognitive deterioration.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies

Aims/hypothesis We systematically reviewed and summarised prospective data relating diabetes status to changes in cognitive function over time. Methods Published reports of longitudinal studies that described assessment of cognitive function in people with diabetes were sought. Studies were included if they assessed cognitive function in participants with diabetes at the beginning and at follow-up. Studies were excluded if they had (1) a follow-up period of less than 1 year, (2) a rate of loss to follow-up in excess of 30%, or (3) described selected subgroups. Change in cognitive function was recorded as either the mean change in score and/or the proportion of individuals developing various degrees of change in cognitive function. A pooled estimate was calculated for the latter. Results Of 1,165 abstracts and titles initially identified, 25 articles met the inclusion and exclusion criteria. Individuals with diabetes had a 1.2- to 1.5-fold greater change over time in measures of cognitive function than those without diabetes. When assessed by the Mini-Mental State Exam and the Digit Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive decline 1.2-fold (95% CI 1.05–1.4) and 1.7-fold (95% CI 1.3–2.3), respectively . The odds of future dementia increased 1.6-fold (95% CI 1.4–1.8). Conclusions/interpretation Compared to people without diabetes, people with diabetes have a greater rate of decline in cognitive function and a greater risk of cognitive decline. Cognitive dysfunction should therefore be added to the list of chronic complications of diabetes.     

Two-year decline in vision but not hearing is associated with memory decline in very old adults in a population-based sample

BACKGROUND: Recent cross-sectional research in cognitive aging has demonstrated a robust association between visual acuity, auditory thresholds and cognitive performance in old age. However, the nature of the association is still unclear, particularly with respect to whether sensory and cognitive function are causally related. OBJECTIVE: This study aimed to determine whether marked declines in performance on screening measures of either visual acuity or auditory thresholds have an effect on cognitive decline over 2 years. METHODS: The sample from the Australian Longitudinal Study of Ageing (n = 2,087) were assessed in 1992 and 1994 on measures of sensory and cognitive function as part of a larger clinical assessment. A quasi-experimental design involving comparison of extreme groups using repeated measures MANCOVA with age as a covariate was used. RESULTS: Group performance on measures of hearing, memory, verbal ability and processing speed declined significantly. Decline in visual acuity had a significant effect on memory decline, but not on decline in verbal ability or processing speed. Decline in hearing was not associated with decline in any cognitive domain. CONCLUSION: The common association between visual acuity, auditory thresholds and cognitive function observed in cross-sectional studies appears to be disassociated in longitudinal studies.     

Clinical effect of cerebrovascular atherosclerosis on cognition in Alzheimer’s disease

BackgroundThe association between cerebrovascular atherosclerosis and Alzheimer’s disease (AD) has been examined in many cross-sectional studies; however, there are few data regarding the role of cerebrovascular atherosclerosis on the longitudinal course of cognitive decline in AD. The aim of this study was to examine the progression of cognitive function in AD patients with cerebrovascular atherosclerosis compared to those without atherosclerosis over a two-year period.MethodsForty-seven AD patients with cerebrovascular atherosclerosis and 81 AD patients without atherosclerosis were assessed for cognitive function at the time of diagnosis and again at follow-up after two years. The cognitive functions were evaluated by neuropsychological tests including mini-mental state examination (MMSE) and clinical dementia scale (CDR).ResultsRepeated-measures multivariate analyses showed that there was a significant group-by-time interactions for the temporal changes of the MMSE and CDR between the two groups. The group-by-time interactions remained significant when the atherosclerotic patients were sub-classified into either an extracranial stenosis (EC) group or an intracranial stenosis(IC) group. Comparing either the EC or IC group with the non-atherosclerosis group, there were no main effects by time or group alone, but there were significant group-by-time interactions for the MMSE and CDR.ConclusionsCognitive function worsened more in terms of progressive impairment in AD patients with cerebrovascular atherosclerosis compared to AD patients without cerebrovascular atherosclerosis, regardless of whether the atherosclerosis was extracranial or intracranial.     

The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment

OBJECTIVES: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. DESIGN: Validation study. SETTING: A community clinic and an academic center. PARTICIPANTS: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). MEASUREMENTS: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. RESULTS: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). CONCLUSION: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.     

Cognitive Training Program to Improve Working Memory in Older Adults with MCI

ABSTRACT

Objectives: Deficits in working memory (WM) are associated with age-related decline. We report findings from a clinical trial that examined the effectiveness of Cogmed, a computerized program that trains WM. We compare this program to a Sham condition in older adults with Mild Cognitive Impairment (MCI). Methods: Older adults (N = 68) living in the community were assessed. Participants reported memory impairment and met criteria for MCI, either by poor delayed memory or poor performance in other cognitive areas. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Delayed Memory Index) and the Clinical Dementia Rating scale (CDR) were utilized. All presented with normal Mini Mental State Exams (MMSE) and activities of daily living (ADLs). Participants were randomized to Cogmed or a Sham computer program. Twenty-five sessions were completed over five to seven weeks. Pre, post, and follow-up measures included a battery of cognitive measures (three WM tests), a subjective memory scale, and a functional measure.Results: Both intervention groups improved over time. Cogmed significantly outperformed Sham on Span Board and exceeded in subjective memory reports at follow-up as assessed by the Cognitive Failures Questionnaire (CFQ). The Cogmed group demonstrated better performance on the Functional Activities Questionnaire (FAQ), a measure of adjustment and far transfer, at follow-up. Both groups, especially Cogmed, enjoyed the intervention.Conclusions: Results suggest that WM was enhanced in both groups of older adults with MCI. Cogmed was better on one core WM measure and had higher ratings of satisfaction. The Sham condition declined on adjustment.     

Does Low to Moderate Alcohol Intake Protect Against Cognitive Decline in Older People?

OBJECTIVES: To determine whether low to moderate alcohol intake is protective against cognitive decline in older people. DESIGN: Prospective cohort study. SETTING: Community‐based study in Ireland, the Netherlands, and Scotland. PARTICIPANTS: Five thousand eight hundred four people (3,000 women) aged 70 to 82 and randomized to pravastatin or placebo in the Prospective Study of Pravastatin in the Elderly at Risk. MEASUREMENTS: Alcohol consumption was determined at study baseline. Serial measures of cognitive function over 3.2 years mean follow‐up included Mini‐Mental‐State‐Examination (MMSE), speed of information processing (Stroop and Letter‐Digit Coding tests), and immediate and delayed memory (Picture‐Word Learning test). RESULTS: Forty‐two percent of women and 71% of men were alcohol drinkers. Cognitive performance was better for female drinkers than nondrinkers for all cognitive domains over the 3.2‐year follow‐up; no significant effects were seen for men (linear mixed model, including adjusting for possible confounders). The rate of cognitive decline was similar for drinkers and nondrinkers for all cognitive domains, except for MMSE, which declined significantly less in female drinkers than nondrinkers (linear mixed model attenuated rate of decline=0.05 MMSE units per annum, P=.001). CONCLUSION: Drinking low to moderate amounts of alcohol may delay age‐associated cognitive decline in older women (including slowing deterioration in global cognitive function), but these apparent benefits were not clearly seen in older men.     

Non-valvular atrial fibrillation and cognitive decline: a longitudinal cohort study

OBJECTIVES: non-valvular atrial fibrillation (NVAF) is an established risk factor for thromboembolism and stroke. Small cross-sectional studies suggest associations between NVAF, silent cerebral infarction and decreased cognitive function. We compared change in cognitive function between patients with recent onset NVAF and controls 12 and 36 months after baseline assessment, and examined the impact of anti-thrombotic therapy. DESIGN: prospective longitudinal cohort study with follow-up at 12 and 36 months. SETTING: Sunderland and South Tyneside, North East of England. Participants: community-dwelling men and women aged over 60 with recently identified NVAF or in sinus rhythm, matched for age, sex and general practice (N = 362, 174 NVAF, 188 sinus rhythm). Participants were stratified for use of anti-thrombotic therapy. MEASUREMENTS: assessment included stroke risk factors and a comprehensive battery of neuropsychological tests. RESULTS: at 3 years, 74 cases and 86 controls remained, giving an attrition rate for cases (59%) versus controls (52%); p = 0.15. Analysis of change in cognitive function between baseline and follow-up at 12 and 36 months revealed no clinically important differences between cases and controls, nor between subgroups on aspirin, warfarin or neither. Age and other confounders did not influence the results. CONCLUSIONS: there was no association between overall cognitive decline and NVAF after 3 years' follow-up, nor any apparent effect of anti-thrombotic therapy. This is consistent with our baseline results, but conflicts with previous studies. Cognitive decline is probably multifactorial and any influence of NVAF was not identified in this study.     

Cognitive impairment,depressive symptoms,and functional decline in older people

OBJECTIVES: Although cognitive impairment and depressive symptoms are associated with functional decline, it is not understood how these risk factors act together to affect the risk of functional decline. The purpose of this study is to determine the relative contributions of cognitive impairment and depressive symptoms on decline in activity of daily living (ADL) function over 2 years in an older cohort. DESIGN: Prospective cohort study. SETTING: A U.S. national prospective cohort study of older people, Asset and Health Dynamics in the Oldest Old. PARTICIPANTS: Five thousand six hundred ninety-seven participants (mean age 77, 64% women, 86% white) followed from 1993 to 1995. MEASUREMENTS: Cognitive impairment and depressive symptoms were defined as the poorest scores: 1.5 standard deviations below the mean on a cognitive scale or 1.5 standard deviations above the mean on validated depression scales. Risk of functional decline in participants with depressive symptoms, cognitive impairment, and both, compared with neither risk factor, were calculated and stratified by baseline dependence. Analyses were adjusted for demographics and comorbidity. RESULTS: Eight percent (n = 450) of subjects declined in ADL function. In participants who were independent in all ADLs at baseline, the relative risk (RR) of 2-year functional decline was 2.3 (95% confidence interval (CI) = 1.7-3.1) for participants with cognitive impairment, 1.9 (95% CI = 1.3-2.6) for participants with depressive symptoms, and 2.4 (95% CI = 1.4-3.7) for participants with cognitive impairment and depressive symptoms. In participants who were dependent in one or more ADLs at baseline, RR of 2-year functional decline was 1.9 (95% CI = 1.2-2.8) for participants with cognitive impairment, 0.6 (95% CI = 0.3-1.3) for participants with depressive symptoms, and 1.5 (95% CI = 0.8-2.6) for participants with cognitive impairment and depressive symptoms. CONCLUSIONS: In participants with no ADL dependence at baseline, cognitive impairment and depressive symptoms are risk factors for decline, but that, in participants with dependence in ADL at baseline, cognitive impairment, but not depressive symptoms, is a risk factor for additional decline.     

Forced expiratory volume in 1 second and cognitive aging in men

OBJECTIVES: To evaluate forced expiratory volume in 1 second (FEV₁, a measure of overall lung function), long‐term average FEV₁, and rate of decline in FEV₁ in relation to cognition and cognitive decline in older men. DESIGN: Prospective observational study. SETTING: Community‐based population. PARTICIPANTS: Eight hundred sixty‐four older men from the Normative Aging Study. MEASUREMENTS: Starting in 1984, participants underwent triennial clinical evaluations. Lung function assessments provided estimates of FEV₁. Cognitive assessments entailing tests of several cognitive abilities began in 1993. FEV₁ measured approximately 12 years before baseline cognitive testing, average FEV₁ over the 12‐year period, and rate of change in FEV₁ were all evaluated in relation to baseline and change in performance on the cognitive tests. RESULTS: In multivariable‐adjusted analyses, associations between FEV₁ and baseline cognitive scores were mixed, although average FEV₁ predicted significantly better performance on tests of visuospatial ability (P=.04) and general cognition (P=.03). Higher FEV₁ was more consistently associated with slower cognitive decline, but only the association between historical FEV₁ and attention was significant (difference per standard deviation in FEV₁=0.056, P=.05). Rate of FEV₁ decline was not consistently associated with cognitive function or decline. Findings were generally similar or stronger in men who had never smoked. To account for potential bias due to selective attrition, inverse probability of censoring weights were applied to the cognitive decline analyses, yielding slightly larger estimates; the inadequate prognostic power of the censoring models limited this approach. CONCLUSION: Overall, the data provide limited evidence of an inverse association between FEV₁ and cognitive aging.     

Multidimensional risk assessment versus age as criterion for retirement of airline pilots.

OBJECTIVE: To determine whether airline pilots over the age of 60 pose a hazard to aviation safety and whether risk assessment could replace age-based retirement. DATA SOURCES: A computer-assisted literature search (MEDLINE), expert consultation, and government reports. STUDY SELECTION: Original studies on flight performance and pilot age; sudden incapacitation, neuropsychological testing, and/or medication use in pilots; and/or non-invasive testing for predicting sudden death or stroke in asymptomatic subjects. DATA EXTRACTION: Pertinent results and methods data were abstracted from the 49 included studies. DATA SYNTHESIS: No study on aircraft accidents or pilot performance has shown an increased accident risk for over-60-year-old pilots. Normal age-related cognitive changes probably have minimal impact on aviation safety up to age 70, given above average health, education, and experience in airline pilots. Cognitive tests have not been validated for predicting flight performance safety, but they can detect early stages of cognitive disease. Cardiovascular incapacitation risk increases with age, but risk factor profiles and non-invasive tests could identify pilots with non-acceptable risk. CONCLUSIONS: An improved medical certification test could identify those pathologic conditions that might occur more frequently in older subjects. If pilots also underwent adequate performance testing, a gradual increase of the retirement age to approximately age 70 would seem justified. In the future, a longitudinal database should be established to validate medical tests for their ability to predict a pilot's accident risk. Using individual pilots as their own controls might be more sensitive than using population-based norm values. Progress in this field would advance medical assessment for other groups such as air traffic controllers or automobile drivers.     

Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss

BACKGROUND: The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/- 5 years, range 73-87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. RESULTS: All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 + 5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups, and prostate-specific antigen levels did not change significantly. CONCLUSION: No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.     

Depressive symptoms were a common risk factor for pre-frailty and frailty in patients with Alzheimer’s disease

ObjectivesThis study aimed to investigate factors associated with frailty in patients with mild to moderate Alzheimer’s disease (AD).MethodsOne hundred fifty-seven outpatients aged 65 years or older with mild to moderate AD were enrolled from January 2018 to December 2018. Cognitive status, depressive mood, activities of daily livings (ADLs), body mass index, handgrip strength (HGS), usual gait speed (UGS), and serum levels of 25-hydroxyvitamin D, hemoglobin (Hb), albumin, and creatinine were assessed. Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: fatigue, resistance, ambulation, illness, and unintentional weight loss.ResultsThe prevalence of frailty was 15.9%. Those classified as being frail were significantly older, had worse cognitive function, worse ADLs, slower UGS, and lower level of Hb compared to those classified as being pre-frail and those robust, respectively. The pre-frail group was significantly older, had worse ADLs, and slower UGS compared to the robust group. Both the frail and pre-frail groups had more depressive symptoms and weaker HGS than the robust group. Multiple logistic regression analysis showed that cognitive function, UGS, level of Hb, and depressive symptoms were associated with frailty, and that only depressive symptoms were associated with pre-frailty.ConclusionsDepressive symptoms were a common risk factor for pre-frailty and frailty in patients with AD. Hb levels and UGS were associated with being frail. Preventing frailty in patients with AD should be approached from both physiological and psychological aspects.     

Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials

The objective of this study was to identify reliable and valid instruments to measure cognitive impairment in systemic lupus erythematosus (SLE), and to define minimally important change of cognitive impairment in SLE for clinical trials. Neurocognitive measures used in randomized clinical trials in SLE were reviewed, and response criteria were developed using consensus expert opinion. The definition of cognitive impairment in the ACR nomenclature for neuropsychiatric lupus syndrome was adopted. Cognitive impairment is a deficit of 2.0 or more standard deviations (SD) below the mean, compared to normative data, in the key domains of attention, memory and psychomotor speed. Cognitive decline is defined as a deficit of 1.5-1.9 SD below the mean. Focal decline is defined if impairment exists in one or more measures within one domain, and multifocal decline if impairment exists on measures spanning two or more domains. The combination of ACR neuropsychological battery and the Cognitive Symptoms Inventory (CSI) is recommended to quantitate cognitive function. A clinically important response is defined as an improvement of > or = 1.0 SD with an effect size of 1.0 in the key domains of the ACR neuropsychological testing, and an improvement of > or = 1.0 SD with an effect size of 1.0 in functional performance of the CSI.     

A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults

OBJECTIVES: To determine whether cardiorespiratory fitness at baseline is associated with maintenance of cognitive function over 6 years or with level of cognitive function on tests performed 6 years later in a longitudinal study of healthy older people. DESIGN: Prospective cohort. SETTING: Community-based study of noninstitutionalized adults aged 55 and older living in Sonoma, California. PARTICIPANTS: Three hundred forty-nine cohort members without evidence of cardiovascular disease, musculoskeletal disability, or cognitive impairment at baseline. MEASUREMENTS: Cardiorespiratory fitness measures were based on a standard treadmill exercise test protocol and included peak oxygen consumption (peak VO2), treadmill exercise duration, and oxygen uptake efficiency slope (OUES). Cognitive function was evaluated at baseline with a modified Mini-Mental State Examination (mMMSE) and after 6 years of follow-up with a detailed cognitive test battery that included the full MMSE, three tests of attention/executive function, two measures of verbal memory, and two tests of verbal fluency. RESULTS: Participants with worse cardiorespiratory fitness at baseline experienced greater decline on the mMMSE over 6 years (mean mMMSE decline (95% confidence interval) by baseline peak VO2 tertile: lowest = -0.5 (-0.8 to -0.3), middle = -0.2 (-0.5-0.0), highest = 0.0 (-0.3-0.2), P =.002 for trend over tertiles). Participants with worse baseline cardiorespiratory fitness also performed worse on all cognitive tests conducted 6 years later. Results were similar for analyses based on peak VO2, treadmill exercise duration, and OUES. After adjustment for demographic and health-related covariates, measures of cardiorespiratory fitness were associated most strongly with measures of global cognitive function and attention/executive function. CONCLUSION: Baseline measures of cardiorespiratory fitness are positively associated with preservation of cognitive function over a 6-year period and with levels of performance on cognitive tests conducted 6 years later in healthy older adults. High cardiorespiratory fitness may protect against cognitive dysfunction in older people.     

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.