Minna Rusanen

Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia

BACKGROUND Smoking is a risk factor for several life-threatening diseases, but its long-term association with dementia is controversial and somewhat understudied. Our objective was to investigate the long-term association of amount of smoking in middle age on the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD) several decades later in a large, diverse population. METHODS We analyzed prospective data from a multiethnic population-based cohort of 21,123 members of a health care system who participated in a survey between 1978 and 1985. Diagnoses of dementia, AD, and VaD made in internal medicine, neurology, and neuropsychology were collected from January 1, 1994, to July 31, 2008. Multivariate Cox proportional hazards models were used to investigate the association between midlife smoking and risk of dementia, AD, and VaD. RESULTS A total of 5367 people (25.4%) were diagnosed as having dementia (including 1136 cases of AD and 416 cases of VaD) during a mean follow-up period of 23 years. Results were adjusted for age, sex, education, race, marital status, hypertension, hyperlipidemia, body mass index, diabetes, heart disease, stroke, and alcohol use. Compared with nonsmokers, those smoking more than 2 packs a day had an elevated risk of dementia (adjusted hazard ratio [HR], 2.14; 95% CI, 1.65-2.78), AD (adjusted HR, 2.57; 95% CI, 1.63-4.03), and VaD (adjusted HR, 2.72; 95% CI, 1.20-6.18). CONCLUSIONS In this large cohort, heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest that the brain is not immune to long-term consequences of heavy smoking.

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.

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.

Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study

Abstract.  Hooshmand B, Solomon A, Kåreholt I, Rusanen M, Hänninen T, Leiviskä J, Winblad B, Laatikainen T, Soininen H & Kivipelto M (Aging Research Center, Karolinska Institutet, Stockholm, Sweden; KI Alzheimer’s Disease Research Center (KI‐ADRC), Karolinska Institutet, Stockholm, Sweden; National Institute for Health and Welfare (THL), Helsinki, Finland; University of Eastern Finland, Institute of Clinical Medicine, and University Hospital, Kuopio, Finland). Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. J Intern Med 2012; 271: 204–212.

Heart Diseases and Long-Term Risk of Dementia and Alzheimer's Disease: A Population-Based CAIDE Study

BACKGROUND Many cardiovascular risk factors are shown to increase the risk of dementia and Alzheimers disease (AD), but the impact of heart disease on later development of dementia is still unclear. OBJECTIVE The aim of the study was to investigate the long-term risk of dementia and Alzheimers disease (AD) related to midlife and late-life atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) in a population-based study with a follow-up of over 25 years. METHODS Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982, or 1987). Re-examinations were carried out in 1998 and 2005-2008. Altogether 1,510 (75.5%) persons participated in at least one re-examination, and 127 (8.4%) persons were diagnosed with dementia (of which 102 had AD). RESULTS AF in late-life was an independent risk factor for dementia (HR 2.61, 95% CI 1.05-6.47; p = 0.039) and AD (HR 2.54, 95% CI 1.04-6.16; p = 0.040) in the fully adjusted analyses. The association was even stronger among the apolipoprotein E (APOE) ε4 non-carriers. Late-life HF, but not CAD, tended to increase the risks as well. Heart diseases diagnosed at midlife did not increase the risk of later dementia and AD. CONCLUSION Late-life heart diseases increase the subsequent risk of dementia and AD. Prevention and effective treatment of heart diseases may be important also from the perspective of brain health and cognitive functioning.

Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia : A Population Based CAIDE Study

BACKGROUND Previous research indicates that persons with chronic obstructive pulmonary disease (COPD) and asthma may have more cognitive impairment compared to persons without these diseases. However, there are no previous studies regarding long-term effects of these diseases on the risk of clinically diagnosed mild cognitive impairment (MCI) and dementia. We examined the association between midlife and late-life self-reported COPD and asthma and the lifelong risk of cognitive impairment (MCI/dementia) in a population-based study with a follow-up of over 25 years. METHODS Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). Re-examinations were carried out in 1998 and 2005-8 (N=1511, 75.6 %) during which 172 persons were diagnosed with MCI and 117 with dementia. RESULTS Midlife COPD (HR 1.85, 95% CI 1.05 - 3.28), asthma (HR 1.88, 95% CI 0.77 - 4.63) and both pulmonary diseases combined (HR 1.94, 95% CI 1.16 - 3.27) increased the later risk of cognitive impairment even after full adjustments. However, pulmonary diseases diagnosed later in life seemed to be inversely related to cognitive impairment (fully adjusted model for both pulmonary diseases combined HR 0.42, 95% CI 0.19 - 0.93). CONCLUSIONS In this population-based study, with more than 25 years of follow-up, midlife COPD and asthma were associated with an almost two-fold risk of MCI and dementia later in life. Pulmonary diseases diagnosed later in life seemed to have an inverse relationship with cognitive impairment probably reflecting survival bias.

Midlife Smoking, Apolipoprotein E and Risk of Dementia and Alzheimer's Disease: A Population-Based Cardiovascular Risk Factors, Aging and Dementia Study

Aim: To elucidate the effect of midlife smoking on the risk of dementia and Alzheimer’s disease (AD), and the possible modification of this relation by the apolipoprotein E (APOE) Ε4. Methods: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were randomly selected from population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). After an average follow-up of 21 years, 1,449 persons (73%) aged 65–79 years took part in a reexamination in 1998. Results: Smoking in midlife increased the risk of dementia (odds ratio, OR: 4.93; 95% CI: 1.51–16.11) and AD (OR: 6.56; 95% CI: 1.80–23.94) among the APOE Ε4 carriers, but not among the APOE Ε4 noncarriers. Conclusion: Midlife smoking was associated with an increased risk of dementia and AD later in life only among those individuals carrying the APOE Ε4 allele. These results suggest that the association between smoking and AD may be complex and vary according to genotype.

Differential Hypometabolism Patterns according to Mild Cognitive Impairment Subtypes

Aims: The present study investigated cerebral glucose metabolism and structural atrophy in controls and subjects with mild cognitive impairment (MCI). Methods: The study included 13 controls, 7 MCI subjects considered as prodromal Alzheimer’s disease (MCI of the Alzheimer type, aMCI) and 7 MCI subjects having cognitive decline due to other causes, established by clinical evaluation (MCI of the non-Alzheimer type, naMCI). Glucose metabolism in the frontal, parietal and posterior cingulate cortices, the hippocampus and parahippocampal gyrus was evaluated using Statistical Parametric Mapping 2 (SPM2). Structural analysis of the whole-brain grey matter was performed with voxel-based morphometry in SPM2. Results: Significant hypometabolism was found in the medial temporal lobe in aMCI subjects compared to the controls and naMCI subjects. In addition, both the aMCI and naMCI patients had hypometabolism of the posterior cingulum relative to controls. The naMCI subjects showed atrophy of frontal and occipital areas compared to controls and aMCI patients, whereas the aMCI subjects did not show atrophy compared to the other groups. Conclusion: aMCI subjects have reduced glucose uptake levels, particularly in areas susceptible to pathological changes in Alzheimer’s disease, and the changes are more pronounced in aMCI than naMCI subjects. Our results also suggest that functional changes may be more prominent than structural changes in MCI.

Late-life cynical distrust, risk of incident dementia, and mortality in a population-based cohort

Objective: We investigated the association between late-life cynical distrust and incident dementia and mortality (mean follow-up times of 8.4 and 10.4 years, respectively) in the Cardiovascular Risk Factors, Aging and Dementia Study. Methods: Cynical distrust was measured based on the Cook-Medley Scale and categorized into tertiles. Cognitive status was evaluated with a 3-step protocol including screening, clinical phase, and differential diagnostic phase. Dementia was diagnosed according to DSM-IV criteria. Complete data on exposure, outcome, and confounders were available from 622 persons (46 dementia cases) for the dementia analyses and from 1,146 persons (361 deaths) for the mortality analyses. Age, sex, systolic blood pressure, total cholesterol, fasting glucose, body mass index, socioeconomic background, smoking, alcohol use, self-reported health, and APOE genotype were considered as confounders. Results: Cynical distrust was not associated with dementia in the crude analyses, but those with the highest level of cynical distrust had higher risk of dementia after adjusting for confounders (relative risk 3.13; 95% confidence interval [CI] 1.15–8.55). Higher cynical distrust was associated with higher mortality in the crude analyses (hazard ratio 1.40; 95% CI 1.05–1.87) but the association was explained by confounders (adjusted hazard ratio 1.19; 95% CI 0.86–1.61). Conclusions: Higher cynical distrust in late life was associated with higher mortality, but this association was explained by socioeconomic position, lifestyle, and health status. Association between cynical distrust and incident dementia became evident when confounders were considered. This novel finding suggests that both psychosocial and lifestyle-related risk factors may be modifiable targets for interventions. We acknowledge the need for larger replication studies.

Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial

The 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.