Tiia Ngandu

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

BACKGROUND 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. METHODS 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. FINDINGS 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). INTERPRETATION 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. FUNDING Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimers 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.

Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study.

BACKGROUND Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles. METHODS Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of beta coefficients and the dementia risk score was the sum of these individual scores (range 0-15). FINDINGS Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (> or = 47 years), low education (< 10 years), hypertension, hypercholesterolaemia, and obesity. The dementia risk score predicted dementia well (area under curve 0.77; 95% CI 0.71-0.83). The risk of dementia according to the categories of the dementia risk score was 1.0% for those with a score of 0-5, 1.9% for a score of 6-7, 4.2% for a score of 8-9, 7.4% for a score of 10-11, and 16.4% for a score of 12-15. When the cut-off of 9 points or more was applied the sensitivity was 0.77, the specificity was 0.63, and the negative predictive value was 0.98. INTERPRETATION The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.

Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE Study

Caffeine stimulates central nervous system on a short term. However, the long-term impact of caffeine on cognition remains unclear. We aimed to study the association between coffee and/or tea consumption at midlife and dementia/Alzheimers disease (AD) risk in late-life. Participants of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were randomly selected from the survivors of a population-based cohorts previously surveyed within the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or 1987 (midlife visit). After an average follow-up of 21 years, 1409 individuals (71%) aged 65 to 79 completed the re-examination in 1998. A total of 61 cases were identified as demented (48 with AD). Coffee drinkers at midlife had lower risk of dementia and AD later in life compared with those drinking no or only little coffee adjusted for demographic, lifestyle and vascular factors, apolipoprotein E epsilon4 allele and depressive symptoms. The lowest risk (65% decreased) was found in people who drank 3-5 cups per day. Tea drinking was relatively uncommon and was not associated with dementia/AD. Coffee drinking at midlife is associated with a decreased risk of dementia/AD later in life. This finding might open possibilities for prevention of dementia/AD.

Education and dementia What lies behind the association

Background: Low education seems to be associated with an increased risk of dementia and Alzheimer disease (AD). People with low education have unhealthier lifestyles and more cardiovascular risk factors, but it is unclear how this affects the association between education and dementia. Methods: Participants of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals (72%) aged 65 to 79 participated in a re-examination in 1998. Results: Compared to individuals with formal education of 5 years or less, those with 6 to 8 years of education had OR of 0.57 (95% CI 0.29 to 1.13), and those with 9 years of education or more had OR of 0.16 (95% CI 0.06 to 0.41) for dementia. The corresponding ORs for AD were 0.49 (0.24 to 1.00) and 0.15 (0.05 to 0.40). The associations remained unchanged after adjustments for several demographic, socioeconomic, vascular, and lifestyle characteristics. The results were similar among both men and women. ApoE4 did not modify the association, but the risk of dementia and AD was very low among ApoE4 noncarriers with high education. Conclusions: The association between low education and dementia is probably not explained by the unhealthy lifestyles of the less educated compared with higher educated persons. Higher educated persons may have a greater cognitive reserve that can postpone the clinical manifestation of dementia. Unhealthy lifestyles may independently contribute to the depletion of this reserve or directly influence the underlying pathologic processes. GLOSSARY: AD = Alzheimer disease; CAIDE = Cardiovascular Risk Factors, Aging and Dementia; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; MMSE = Mini-Mental State Examination; NINCDS-ADRDA = National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association; SBP = systolic blood pressure.

Fat intake at midlife and cognitive impairment later in life : a population-based CAIDE study

To investigate the association of midlife dietary fat intake to cognitive performance, and to the occurrence of clinical mild cognitive impairment (MCI) later in life in a non‐demented population.

Fat Intake at Midlife and Risk of Dementia and Alzheimer’s Disease: A Population-Based Study

Background: Lifestyle and vascular factors have been linked to dementia and Alzheimer’s disease (AD), but the role of dietary fats in the development of dementia is less clear. Methods: Participants were derived from random, population-based samples initially studied in midlife (1972, 1977, 1982, or 1987). Fat intake from spreads and milk products was assessed using a structured questionnaire and an interview. After an average follow-up of 21 years, a total of 1,449 (73%) individuals aged 65–80 years participated in the re-examination in 1998. Altogether 117 persons had dementia. Results: Moderate intake of polyunsaturated fats at midlife decreased the risk of dementia even after adjustment for demographic variables, other subtypes of fats, vascular risk factors and disorders, and apolipoprotein E (ApoE) genotype (OR 0.40, CI 0.17–0.94 for the 2nd quartile vs. 1st quartile), whereas saturated fat intake was associated with an increased risk (OR 2.45, CI 1.10–5.47 for the 2nd quartile). The associations were seen only among the ApoE Ε4 carriers. Conclusions: Moderate intake of unsaturated fats at midlife is protective, whereas a moderate intake of saturated fats may increase the risk of dementia and AD, especially among ApoE Ε4 carriers. Thus, dietary interventions may potentially modify the risk of dementia, particularly among genetically susceptible individuals.

Apolipoprotein E ɛ4 magnifies lifestyle risks for dementia: a population‐based study

The risk of dementia and Alzheimers disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE ɛ4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population‐based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow‐up of 21 years, 1449 individuals (72.5%) aged 65–79 years were re‐examined in 1998. The apoE ɛ4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR]= 2.83, 95% confidence interval [CI]ɛ1.61–4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE ɛ4 carriers. Furthermore, low–moderate intake of polyunsaturated, and moderate–high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE ɛ4 carriers. Composite effect of the lifestyle factors was particularly seen among the ɛ4 carriers (OR = 11.42, 95% CI = 1.94–67.07 in the 4th quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE ɛ4 carriers. The apoE ɛ4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and progress

Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi‐center, randomized, controlled trial ongoing in Finland.

Serum total cholesterol, statins and cognition in non-demented elderly

BACKGROUND The association between serum total cholesterol (TC), lipid-lowering drugs and cognition in the elderly is currently controversial. OBJECTIVE To investigate the relationship between TC, lipid-lowering drugs and cognitive functions in non-demented elderly. DESIGN AND SETTING Participants of the Cardiovascular risk factors, aging and dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. Analyses are based on 1382 non-demented participants re-examined in 1998 after an average follow-up of 21 years. RESULTS High midlife TC was associated with poorer late-life episodic memory and category fluency. TC decreased in most individuals over time. A more pronounced decrease was related to poorer late-life episodic memory and psychomotor speed, but not if subjects used statins. CONCLUSIONS The TC-cognition relationship seems bidirectional. High midlife TC is associated with poorer late-life cognition, but decreasing TC after midlife may reflect poorer cognitive status. Statins may be beneficial for cognition in non-demented elderly.

Midlife and late-life body mass index and late-life dementia: results from a prospective population-based cohort.

BACKGROUND Obesity has been consistently associated with dementia. The role of certain risk factors of dementia may change during life, and the importance of having a life-course perspective has been acknowledged. OBJECTIVE The aim of this study was to investigate the association of midlife and late-life body mass index (BMI) with late-life dementia/Alzheimers disease (AD) and whether the association was independent of other obesity-related co-morbidities. METHODS The association between midlife BMI (mean age 50.2, SD 6.0) and late-life BMI (mean age 71.2, SD 4.0) and incident dementia later in life (mean age 75.7, SD 5.0) were investigated among 1,304 participants of the longitudinal population-based Cardiovascular risk factors, Aging and Dementia (CAIDE) study, conducted in Eastern Finland. The duration of follow-up was 26 years. The diagnosis of dementia was based on DSM-IV criteria and the probable and possible AD on the NINCDS-ADRDA criteria. RESULTS Higher midlife BMI was associated with higher risk of incident dementia (adjusted HR, 95% CI 1.07, 1.00-1.14). However, decrease in BMI from midlife to late-life was associated with higher risk of dementia (1.14, 1.03-1.25 for one-unit decrease) and AD (1.20, 1.09-1.33). High late-life BMI was associated with lower risk of AD (0.89, 0.81-0.98) but the association with dementia was less evident (0.94, 0.86-1.03). CONCLUSION Higher midlife BMI is related to higher risk of dementia and AD, independently of obesity-related risk factors and co-morbidities. Steeper decrease of BMI and low late-life BMI are associated with higher risk of dementia and AD. These findings highlight the importance of life-course perspective when assessing the association between BMI and cognition.