Ingemar Kåreholt

Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease

BACKGROUND 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 Alzheimers disease (AD). METHODS 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. FINDINGS 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 epsilon4 carriers. INTERPRETATION 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.

Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study.

Abstract Objective To evaluate the relation between midlife alcohol consumption and mild cognitive impairment and dementia in old age, and the possible modification of this relation by apolipoprotein E. Design Prospective, population based study. Setting Populations of Kuopio and Joensuu, eastern Finland. Participants Of 1464 men and women aged 65-79 years randomly selected from population based samples studied in 1972 or 1977, 1018 (70%) were re-examined in 1998 (after an average follow up of 23 years). Main outcome measures Mild cognitive impairment and dementia in old age. Results Participants who drank no alcohol at midlife and those who drank alcohol frequently were both twice as likely to have mild cognitive impairment in old age as those participants who drank alcohol infrequently. The risk of dementia related to alcohol drinking was modified by the presence of the apolipoprotein e4 allele. The carriers of apolipoprotein e4 had an increased risk of dementia with increasing alcohol consumption: compared with non-carriers who never drank, the odds ratio for carriers who never drank was 0.6, for infrequent drinkers it was 2.3, and for frequent drinkers was 3.6 (the overall interaction term “drinking frequency*apolipoprotein e4” was significant (P = 0.04), as were the interactions “infrequent drinking*apolipoprotein e4” (P = 0.02) and “frequent drinking*apolipoprotein e4” (P = 0.03)). Non-carriers of apolipoprotein e4 had similar odds ratios for dementia irrespective of alcohol consumption. Conclusion Alcohol drinking in middle age showed a U shaped relation with risk of mild cognitive impairment in old age. Risk of dementia increased with increasing alcohol consumption only in those individuals carrying the apolipoprotein e4 allele.

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.

Women are more disabled in basic activities of daily living than men only in very advanced ages: A study on disability, morbidity, and mortality from the Kungsholmen Project

OBJECTIVE We explored the effect of morbidity, mortality, and occurrence of new disability on gender differences in activities of daily living (ADL) functioning in different age groups in the elderly population. METHODS All 77+-year-old members of a community-based cohort were clinically examined by physicians, assessed by psychologists, and interviewed by nurses at baseline and after a 3-year interval. Diseases were diagnosed according to ICD-9 and the DSM-III-R criteria for dementia. The Katz index of ADL was used to measure basic functional status. RESULTS After adjustment for socio-demographic characteristics, the oldest women (90+ years) had higher disability prevalence and a tendency for higher long-term disability incidence. Women aged 85+ years also had higher morbidity prevalence. Mortality among disabled subjects was similar for both genders, whereas higher mortality was found in younger nondisabled men (77-84 years). CONCLUSION We conclude that gender differences in disability, morbidity, and mortality vary with age in the elderly population. Gender differences in morbidity and basic functional dependence were evident only in the oldest old. Based on current and previous findings, we speculate that more women may be at higher risk of developing severe disability than men in the advanced ages due to longer survival with slight disability earlier in adult life.

Personality and lifestyle in relation to dementia incidence

Objective: High neuroticism has been associated with a greater risk of dementia, and an active/socially integrated lifestyle with a lower risk of dementia. The aim of the current study was to explore the separate and combined effects of neuroticism and extraversion on the risk of dementia, and to examine whether lifestyle factors may modify this association. Methods: A population-based cohort of 506 older people with no dementia from the Kungsholmen Project, Stockholm, Sweden, was followed up for an average of 6 years. Personality traits were assessed using the Eysenck Personality Inventory. Dementia was diagnosed by specialists according to DSM-III-R criteria. Results: Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27–0.96). When compared to persons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28–0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57–1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57–1.65). Stratified analysis by lifestyle showed that the inverse association of low neuroticism and high extraversion in combination was present only among the inactive or socially isolated persons. Conclusion: Low neuroticism in combination with high extraversion is the personality trait associated with the lowest dementia risk; however, among socially isolated individuals even low neuroticism alone seems to decrease dementia risk.

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.

Pain Treatment in Elderly Persons With and Without Dementia : A population-Based Study of Institutionalized and Home-Dwelling Elderly

AbstractBackground: Several previous studies have reported an undertreatment of pain in elderly persons with dementia. It has also been suggested that persons with dementia may be at risk for inappropriate treatment of pain with psychotropics. Objectives: The objective of this study was to investigate if persons with dementia are as likely as persons without dementia to receive pharmacological pain treatment, after taking into account residential setting and pain-related disorders. We also aimed to investigate whether use of psychotropics is related to pain in persons with and without dementia. Methods: We used baseline data from the SNAC-K (Swedish National Study of Aging and Care — Kungsholmen). We analysed use of analgesics and psychotropics, prevalence of pain-related diagnoses, self-reported pain, dementia status and residential setting in 2610 participants aged >65 years. Results: Of the persons with dementia, 46% used at least one analgesic drug compared with 25% of those without dementia. Although persons with dementia reported pain less frequently than persons without dementia, the prevalence of pain-related diagnoses was similar. After adjustment for individual factors and residential setting (own home/institution), persons with dementia had a higher probability of use of paracetamol (acetaminophen) and psychotropics, whereas there were no significant differences in use of any analgesic, opioids and NSAIDs. Furthermore, having a pain-related diagnosis was associated with use of psychotropics in persons with dementia. Conclusions: Persons with dementia had a higher probability of use of paracetamol and were about as likely as persons without dementia to use any analgesic, opioids and NSAIDs, after adjustment for confounders. This may reflect a recent increased awareness of pain and pain management in persons with dementia, compared with previous studies that have reported an underuse of analgesics in persons with dementia. However, further research is needed to analyse if persons with dementia are appropriately treated for pain with regard to type of analgesic drug, pain intensity, indication, dosage and regimen.

The effect of point of reference on the association between self-rated health and mortality

This study examines the effect of point of reference on the predictive validity of self-rated health for mortality in a 5-year follow-up period. Two self-rated health measures are examined: an age group comparative question and a global question with no explicit point of reference. The baseline data (SweOld) is a nationally representative interview survey among Swedish people aged 77+ in 1992. Mortality for the 1992-1996 period was analysed using Cox proportional hazards regression models. Age-referential self-rated health was found to be a better predictor of elderly mens mortality both in non-adjusted models and in models adjusting for age and both self-rated health measures. In separate analyses, both measures were found to be equally strong predictors of womens mortality. When adding both measures into the model simultaneously, the age-referential question lost much of its predictive power. The findings suggest that self-rated health measures are not insensitive to differences in question wording.

Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study.

Objective: To examine the relation between serum levels of homocysteine (tHcy) and holotranscobalamin (holoTC), the active fraction of vitamin B12, and risk of incident Alzheimer disease (AD) in a sample of Finnish community-dwelling elderly. Methods: A dementia-free sample of 271 subjects aged 65–79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed up for 7 years to detect incident AD. The association between serum tHcy and holoTC with AD was analyzed with multiple logistic regression after adjusting for several potential confounders, including common vascular risk factors. Results: The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04–1.31) per increase of 1 μmol/L of tHcy at baseline and 0.980 (0.965–0.995) for each increase of 1 pmol/L baseline holoTC. Adjustment for several potential confounders including age, sex, education, APOE ϵ4 allele, body mass index, Mini-Mental State Examination, smoking, stroke, and blood pressure did not alter the associations: ORs (95% CI) for AD became 1.19 (1.01–1.39) for tHcy and 0.977 (0.958–0.997) for holoTC. Adjusting for holoTC attenuated the tHcy–AD link (OR changed from 1.16 to 1.10, 95% CI 0.96–1.25). The holoTC–AD relationship was less influenced by controlling for tHcy (OR changed from 0.980 to 0.984, 95% CI 0.968–1.000). Addition of folate did not change any of the results. Conclusions: This study suggests that both tHcy and holoTC may be involved in the development of AD. The tHcy–AD link may be partly explained by serum holoTC. The role of holoTC in AD should be further investigated.