Abstract Background Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials ...Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score ≥6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle–related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between ...leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD).
Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72·5%) age 65–79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD.
Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio OR 0·48 95% CI 0·25–0·91 and 0·38 0·17–0·85, respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders,
APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the
APOE ɛ4 carriers.
Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.
Abstract Physical activity has been associated with decreased dementia risk in recent studies, but the effects for structural brain changes (i.e. white matter lesions (WML) and/or brain atrophy) have ...remained unclear. The CAIDE participants were a random population-based sample studied in midlife and re-examined on average 21 years later ( n = 2000). A subpopulation ( n = 75; 31 control, 23 MCI, 21 dementia) was MRI scanned at the re-examination. T1-weighted images were used to investigate grey matter (GM) density, and FLAIR-images for WML rating. Persons who actively participated in physical activity at midlife tended to have larger total brain volume ( β 0.12; 95% CI 0.17–1.16, p = 0.10) in late-life than sedentary persons even after adjustments. GM volume was larger among the active ( β 0.19; 95% CI 0.07–1.48, p = 0.03), whereas the association between midlife physical activity and larger WM volume became non-significant ( β 0.03; 95% CI −0.64 to 0.86, p = 0.77) after full adjustments. The differences in the GM density localized mainly in frontal lobes. There was no significant association between midlife physical activity and severe WML later in life after full adjustments (OR 4.20, 95% CI 0.26–69.13, p = 0.32).
Magnetic resonance imaging (MRI) has been suggested as a useful tool in early diagnosis of Alzheimer’s disease (AD). Based on MRI-derived volumes, we studied the hippocampus and entorhinal cortex ...(ERC) in 59 controls, 65 individuals with mild cognitive impairment (MCI) and 48 patients with AD. The controls and individuals with MCI were derived from population-based cohorts. Volumes of the hippocampus and ERC were significantly reduced in the following order: control>MCI>AD. Stepwise discriminant function analysis showed that the most efficient overall classification between controls and individuals with MCI subjects was achieved with ERC measurements (65.9%). However, the best overall classification between controls and AD patients (90.7%), and between individuals with MCI and AD patients (82.3%) was achieved with hippocampal volumes. Our results suggest that the ERC atrophy precedes hippocampal atrophy in AD. The ERC volume loss is dominant over the hippocampal volume loss in MCI, whereas more pronounced hippocampal volume loss appears in mild AD.
Prospective studies on physical activity in relation to the risk for hypertension are scant, particularly in women. This study aimed at finding out whether regular physical activity can reduce the ...risk of hypertension in both men and women, and in subjects with and without overweight. We prospectively followed 8302 Finnish men and 9139 women aged 25 to 64 years without a history of antihypertensive drug use, coronary heart disease, stroke, and heart failure at baseline. Both single and joint associations of physical activity and body mass index with the risk of hypertension were examined using Cox proportional hazard models. During a mean followup of 11 years, there were 1600 incident cases of drug-treated hypertension. Multivariate-adjusted hazards ratios of hypertension associated with light, moderate, and high physical activity were 1.00, 0.63, and 0.59 in men (Ptrend<0.001), and 1.00, 0.82, and 0.71 in women (Ptrend=0.005), respectively. This association persisted both in subjects who were overweight and in those who were not. Multivariate-adjusted hazards ratios of hypertension based at different levels of body mass index (<25, 25 to 29.9, and > or =30) were 1.00, 1.18, and 1.66 for men (Ptrend<0.001), and 1.00, 1.24, and 1.32 for women (Ptrend=0.007), respectively. Further adjustment for baseline systolic blood pressure did not affect the protective effect associated with physical activity, but it weakened markedly the association between body mass index and hypertension. The present study indicates that regular physical activity and weight control can reduce the risk of hypertension. The protective effect of physical activity was observed in both sexes regardless of the level of obesity.
Abstract Objective To examine the association of different levels of occupational, commuting, and leisure-time physical activity with the risk of coronary heart disease (CHD) events. Methods and ...results The study comprised 47,840 Finnish participants aged 25–64 years without history of CHD and stroke at baseline. During a mean follow-up of 18.9 years, 4660 new CHD events were documented. The multivariable-adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, alcohol consumption, smoking, history of diabetes, and other two types of physical activity) hazard ratios (HRs) of CHD events associated with low, moderate, and high occupational activity were 1.00, 0.87, and 0.90 ( Ptrend = 0.019) for men, and 1.00, 0.75, and 0.80 ( Ptrend < 0.001) for women, respectively. The multivariable-adjusted HRs of CHD events associated with low, moderate, and high leisure-time physical activity were 1.00, 0.95, and 0.84 ( Ptrend = 0.026) for men, and 1.00, 0.85, and 0.77 ( Ptrend = 0.003) for women, respectively. Active commuting had a significant inverse association with the risk of CHD events in women but not in men. Conclusion Moderate or high levels of occupational or leisure-time physical activity are associated with a reduced risk of CHD. Daily walking or cycling to and from work is associated with a decreased risk of CHD among women.
Recent research has shown an increased rate of conversion to dementia in subjects with mild cognitive impairment (MCI) compared to controls. However, there are no specific methods to predict who will ...later develop dementia. In the present study, 22 controls and 56 MCI subjects were followed on average for 37 months (max. 60 months) and studied with magnetic resonance imaging (MRI) at baseline to assess changes in brain structure associated to later progression to dementia. Voxel-based morphometry (VBM) was used to investigate gray matter atrophy. During the follow-up, 13 subjects progressed to dementia. At baseline, no differences were detected in age or education between the control and MCI subjects, but they differed by several neuropsychological tests. The stable and progressive MCI subjects differed only by CDR sum of boxes scores and delayed verbal recall, which were also significant predictors of conversion to dementia. At the baseline imaging, the MCI subjects showed reduced gray matter density in medial temporal, temporoparietal as well as in frontal cortical areas compared to controls. Interestingly, the progressive MCI subjects showed atrophy in the left temporoparietal and posterior cingulate cortices and in the precuneus bilaterally, and a trend for hippocampal atrophy when compared to the stable MCI subjects. We conclude that widespread cortical atrophy is present already two and a half years before a clinical diagnosis of dementia can be set.
Abstract The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived ...volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.
Abstract Previous research shows that cardiovascular risk factors in mid-adulthood could increase the risk of dementia later in life, but studies with very long follow-up are still scarce. We ...assessed whether cardiovascular risk factors measured in midlife were associated with dementia mortality during a 40-year follow-up. 10,211 men, aged 40–59 at baseline, from 13 cohorts of the Seven Countries Study were followed for 40 years. Information on cardiovascular risk factors was obtained at baseline from questionnaires and a physical examination. Dementia death was assigned if there was any mention of dementia on the death certificate. Associations between cardiovascular risk factors and death from dementia were estimated through Cox proportional hazards models. We identified 160 dementia deaths during the follow-up. Smoking, hypercholesterolemia, high blood pressure, low forced vital capacity and previous history of cardiovascular disease at baseline were associated with a higher risk of death from dementia in the follow-up. The hazard ratio (HR) of dementia death among heavy smokers was 1.58 (95% confidence interval (CI) 1.03, 2.43) compared to non-smokers. Similarly, the HR (95% CI) among those with systolic BP ≥ 160 or diastolic BP ≥ 95 mm Hg compared to normotensives (< 140/90) was 1.55 (1.02, 2.35). Individuals with the largest forced vital capacity had a lower risk of dying of dementia (HR 0.54, 95% CI 0.30, 0.98). Finally, total serum cholesterol was directly associated with higher risk of dementia mortality ( p for trend = 0.03). In men, cardiovascular risk factors in midlife are associated with increased risk of dementia death later in life.
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