A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.
Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.
In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989.
Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control).
Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.
Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.
Although animal studies have indicated that general anesthetics may result in widespread apoptotic neurodegeneration and neurocognitive impairment in the developing brain, results from human studies are scarce. We investigated the association between exposure to surgery and anesthesia for inguinal hernia repair in infancy and subsequent academic performance.
Using Danish birth cohorts from 1986-1990, we compared the academic performance of all children who had undergone inguinal hernia repair in infancy to a randomly selected, age-matched 5% population sample. Primary analysis compared average test scores at ninth grade adjusting for sex, birth weight, and paternal and maternal age and education. Secondary analysis compared the proportions of children not attaining test scores between the two groups.
From 1986-1990 in Denmark, 2,689 children underwent inguinal hernia repair in infancy. A randomly selected, age-matched 5% population sample consists of 14,575 individuals. Although the exposure group performed worse than the control group (average score 0.26 lower; 95% CI, 0.21-0.31), after adjusting for known confounders, no statistically significant difference (-0.04; 95% CI, -0.09 to 0.01) between the exposure and control groups could be demonstrated. However, the odds ratio for test score nonattainment associated with inguinal hernia repair was 1.18 (95% CI, 1.04-1.35). Excluding from analyses children with other congenital malformations, the difference in mean test scores remained nearly unchanged (0.05; 95% CI, 0.00-0.11). In addition, the increased proportion of test score nonattainment within the exposure group was attenuated (odds ratio = 1.13; 95% CI, 0.98-1.31).
In the ethnically and socioeconomically homogeneous Danish population, we found no evidence that a single, relatively brief anesthetic exposure in connection with hernia repair in infancy reduced academic performance at age 15 or 16 yr after adjusting for known confounding factors. However, the higher test score nonattainment rate among the hernia group could suggest that a subgroup of these children are developmentally disadvantaged compared with the background population.
The purpose of this study was to clarify the effects of age and education on CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test performances.
We present preliminary data on CERAD test results for a sample of elderly normal Finns (n = 40, age 58-85 years).
Our results show no significant correlation between age and CERAD test results. Significant differences were found between subjects with low versus high education in nine CERAD test scores. The mean scores in the low-education group were near the cut-off point in the naming test, whereas the mean scores of the high-education group nearly reached the ceiling on six test scores. These differences were evident in the wordlist learning test, which has previously been argued to be unaffected by educational level. Savings scores were unaffected by education.
The results underline the importance of taking into account the educational level of persons with subjective memory complaints when screening with CERAD for mild cognitive impairment and preclinical Alzheimer's disease.
Moderate alcohol drinking is suggested to be beneficial for cognitive functions, but the results of previous studies have varied greatly. Little is known about the effects of midlife alcohol drinking on the cognitive functions later in life.
Participants were derived from random, population-based samples studied in Eastern Finland in 1972, 1977, 1982, or 1987. A total of 1,341 participants were reexamined in 1998, after an average follow-up period of 21 years, at ages 65-79 years.
The participants who did not drink alcohol at midlife had a poorer performance in episodic memory, psychomotor speed, and executive function in late life as compared with infrequent and frequent drinkers, adjusted for sociodemographic and vascular factors. Also late-life nondrinkers had poorer psychomotor speed and executive function. These findings were evident especially among nonsmokers. Further, no interactions between apolipoprotein E4 and alcohol or sex and alcohol were found.
Alcohol drinking both at midlife and later is favorably related to the function in several cognitive domains, including episodic memory, psychomotor speed, and executive function, in late life. However, it is not clear whether the association is causal, what is the possible mechanism, and what would be a safe limit of drinking for the best cognitive function.
Anthropometric measurement is a noninvasive and cost-efficient method for nutritional assessment. The study aims to present age- and gender-specific anthropometric reference data for Swedish elderly in relation to common medical conditions, and also formulate prediction equations for such anthropometric measurements.
A cross-sectional study among random heterogeneous sample of 3360 subjects, aged 60-99 years, from a population study 'Good Aging in Scania. Means (±s.d.) and percentiles for height, weight, waist-, hip-, arm-, calf circumferences, triceps- (TST) and subscapular skinfold thickness (SST), body mass index (BMI), waist-hip ratio (WHR) and arm muscle circumference (AMC) were presented. The values were estimated based on the prevalence of myocardial infarction (MI), cardiac failure (CHF), stroke, cognitive impairment, dementia and dependence in daily living activities (ADL). Linear regression analysis was used to formulate the prediction equations.
Mean BMI was 27.5±5.8?kg/m(2) (men) and 27.2±8.1?kg/m(2) (women). WHR was higher among men (Men: 0.98±0.3, women: 0.87±0.2), except at age 85+ (women: 0.91±0.6). TST was 6.7±0.4?mm higher among women. Men with MI had BMI: 28.6±4.8?kg/m(2) and SST: 21±9.2?mm, whereas subjects with dementia had lower weight (by 9.5±2.9?kg) compared with the non-demented. ADL-dependent women had BMI= 29.0±3.9?kg/m(2), TST=19.2±1.3?mm.
New normative data on gender- and age-specific anthropometrics on the general elderly population are presented. Cardiovascular diseases are associated with subcutaneous and central adiposity opposed to fat loss with dementia. ADL dependence indicates inadequate physical activity. The prediction models could be used as possible indicators monitoring physical activity and adiposity among the general elderly population hence potential health indicators in health promotion.
Anxiety symptoms are highly prevalent in elders with mild cognitive disorders, but little is known about the associations of specific anxiety disorders to mild cognitive disorders.
To identify the clinical and subclinical anxiety disorders associated with cognitive impairment no dementia (CIND) and to determine whether these associations differ depending on sex and concomitant depressive episodes.
Participants constituted a random sample (n?=?2414) of community-dwelling adults aged 65-96 years. The following clinical and subclinical DSM-IV anxiety disorders were identified with a semi-structured interview: specific phobia, social phobia, agoraphobia, panic disorder, obsessive-compulsive, and generalized anxiety disorder (GAD). Major depressive episodes or minor depression (MDE/MD) were also determined based on the DSM-IV criteria. CIND cases were defined based on Mini-Mental State Examination (MMSE) cut-offs (15th percentile) stratified for age, education, and sex. Potentially confounding variables (age, education, MDE/MD, chronic diseases, and psychotropic drug use) were statistically controlled.
In men, after adjusting for confounding variables, CIND was associated with subclinical GAD (odds ratio (OR): 4.93, 95% confidence interval: 1.84-13.23). Further analyses showed that in men, CIND was related to clinical/subclinical GAD whether MDE/MD was present (7.05, 1.88-26.43) or absent (9.33, 3.24-26.83). In women, CIND was not linked to any clinical or subclinical anxiety disorder.
These results suggest that in community-dwelling elders, GAD is the main anxiety disorder associated with poor global cognitive functioning. Moreover, this association is modified by sex, but not by the presence of depressive episodes.
Aphasia, depression, and cognitive dysfunction are common consequences of stroke, but knowledge of their interrelationship is limited. This 1-year prospective study was designed to evaluate prevalence and course of post-stroke aphasia and to study its psychiatric, neurological, and cognitive correlates. We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65. 8 years) with first-ever ischaemic brain infarction. The patients were clinically examined, and presence and type of aphasia were evaluated during the 1st week after stroke and 3 and 12 months later. Psychiatric and neuropsychological evaluations were performed 3 and 12 months after stroke. Aphasia was diagnosed in 34% of the patients during the acute phase, and two thirds of them remained so 12 months later. Seventy percent of the aphasic patients fulfilled the DSM-III-R criteria of depression 3 months and 62% 12 months after stroke. The prevalence of major depression increased from 11 to 33% during the 12-month follow-up period. The non-verbal neuropsychological test performance in the aphasic patients was significantly inferior to that of the patients with dominant hemisphere lesion without aphasia. One third of the patients with ischaemic stroke suffer from communicative disorders which seem to increase the risk of depression and non-verbal cognitive deficits. Although the prevalence of depression in aphasic patients decreases in the long term, the proportion of patients suffering from major depression seems to increase. We emphasize the importance of the multidimensional evaluation of aphasic stroke patients.
To investigate whether presence of the APOE epsilon4 allele is related to the pathologic progression of preclinical Alzheimer disease (AD), as reflected by change in Mini-Mental State Examination (MMSE) scores among persons in the preclinical phase of AD, and cognitively intact adults confirmed as dementia-free during the 6-year assessment period.
In a population-based sample, participants were stratified according to APOE genotype (epsilon4 or non-epsilon4) and whether they received a diagnosis of AD at the end of either a 3- or 6-year assessment period. Participants were aged 75 years and older, and were nondemented at baseline. At the end of the 3-year period, 17.2% of non-epsilon4 and 26.7% of epsilon4 carriers became demented. For the 6-year period those percentages were 11.2% for non-epsilon4 carriers and 16.9% for epsilon4-carriers.
Individuals in the preclinical phase of AD showed greater decline on the MMSE as compared to nondemented adults. However, the decline was most marked in the 3 years prior to clinical diagnosis. Further, APOE-epsilon4 genotype did not modify the rate of decline among to-be-demented participants, as well as individuals who would remain free of AD.
Although possession of the APOE epsilon4 allele is a risk factor for AD in old age, it does not modify the progression of the disease during the preclinical period. Further, in the absence of preclinical dementia, APOE did not influence global cognitive change in nondemented persons.
Apolipoprotein E (ApoE) epsilon4 genotype is a well-established risk factor for Alzheimer's disease (AD). However, its effect on predicting conversion from normal to "cognitive impairment, no dementia" (CIND) and from CIND to AD is less clear.
We used a nested case-control design from the population-based Canadian Study of Health and Aging (CSHA) to examine the effect of ApoE epsilon4 genotype on the conversion of subjects from normal to CIND and from CIND to AD. We also contrasted these findings with incident cases of AD and vascular dementia (VaD) in the CSHA cohort.
The ApoE epsilon4 genotype was a significant risk factor for conversion from CIND to AD and from normal to AD and VaD. However, it was not a significant risk factor for conversion from normal to CIND. This effect is robust to adjustment for age, sex and education level. There is significant interaction between the ApoE epsilon4 genotype and age for AD and for conversion from CIND to AD. No interaction between ApoE epsilon4 genotype, sex, age, ethnicity and education level was found in other subgroup analyses. The positive predictive value of ApoE epsilon4 for predicting CIND conversion to AD was 0.48, and the negative predictive value was 0.65.
Possession of an ApoE epsilon4 allele increases the risk of AD developing from CIND. It is also associated with a decrease in the age at onset of AD. Its predictive values do not support its utility as a diagnostic test for predicting progression from CIND to AD, but it may be useful in research studies to enrich study samples that have a higher rate of progression to AD.
Notes
Cites: Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-818446617
Cites: Trans Am Clin Climatol Assoc. 1988;99:100-103503432
PURPOSE: To study gender differences in functional outcome unexpectedly observed in a follow-up study of stroke patients. DESIGN: Prospective study of hospitalized stroke patients, with evaluations in the subacute phase and after one year. SETTING: Geriatric and general medical wards, and geriatric outpatient clinic of a university hospital serving as general hospital for a defined population. SUBJECTS: All stroke patients admitted during a six-month period (n = 165) were considered for inclusion, of whom 87 could be assessed in the subacute phase and 65 after one year. MAIN OUTCOME MEASURES: Motor function assessed by the Sødring Motor Evaluation of Stroke Patients; cognitive function by the Assessment of Stroke and other Brain Damage; and activities of daily living (ADL) function by the Barthel Index. Nursing-home residency registered after one year. RESULTS: Men achieved a significantly better score than women on most of the scales used. The age-adjusted odds for a man to have a higher Barthel score than a woman was 3.1 (95% confidence interval (CI) 1.3-7.0) in the subacute phase and 3.3 (95% CI 1.2-9.0) after one year. Differences of the same magnitude were seen on the subscales of the motor and cognitive tests. The same trend was observed on all items of the Barthel Index. The males had a lower likelihood to be permanent nursing-home residents after one year, the age-adjusted odds ratio for nursing-home residency for females versus males being 6.3 (95% CI 1.2-65.3). CONCLUSION: Women seem to be functionally more impaired by stroke than men.
