Alzheimer Disease: Kivipelto M

Kivipelto M, Solomon A. · No affiliation provided · BMJ. · Pubmed #16690644 links to  free full text

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Kivipelto M, Solomon A. · Aging Research Center, Karolinska Institutet, Gavlegatan 16, S-113 30 Stockholm, Sweden. · J Nutr Health Aging. · Pubmed #18165854 No free full text.

Abstract: Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.

Kivipelto M, Solomon A. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866911 No free full text.

Abstract: Although dementia is usually a late-life syndrome, it is now well known that pathological changes begin quite early in adulthood, outside the classical age borders of geriatric specialties. In order to design effective preventive strategies, adequate information can only be gathered by taking a life-long view of Alzheimer's disease (AD). Dementia risk is the result of exposure to both harmful and protective factors along the life course, and these factors, as well as their impact on the individual's health status, change over time. This review aims at presenting current epidemiological data on serum cholesterol levels and dietary fat intake as risk factors for dementia/AD, and at discussing the reasons and significance of contradictions between various studies. Reducing dementia risk may be possible by influencing the serum lipid profile. A more detailed characterization of the mechanisms behind the association of cholesterol (in both serum and brain) with dementia/AD, mechanisms about which little is currently known, would allow a better translation of research findings into clinical practice.

Jelic V, Kivipelto M, Winblad B. · Karolinska Institutet, Neurotec Department, Division of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · J Neurol Neurosurg Psychiatry. · Pubmed #16306154 links to  free full text

Abstract: Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.

Hiltunen M, Helisalmi S, Kivipelto M, Soininen H. · Kuopion yliopisto, neurologian klinikka, Mediteknia. · Duodecim. · Pubmed #15641511 No free full text.

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Lane RM, Kivipelto M, Greig NH. · Novartis Neuroscience, Novartis Pharmaceuticals Corp., East Hanover, NJ 07936-1080, USA. · Clin Neuropharmacol. · Pubmed #15190239 No free full text.

Abstract: Until recently, the only established function of acetylcholinesterase (AChE) was the termination of cholinergic neurotransmission. Therefore, the use of AChE inhibitors to treat symptoms caused by cholinergic imbalances in Alzheimer disease (AD) represented a rational approach. However, it is now clear that AChE and the cholinergic system may have broader effects in AD. Of particular interest may be signal transduction pathways mediated through cholinergic receptors that promote nonamyloidogenic amyloid precursor protein processing and decrease tau phosphorylation, and the role of AChE in the aggregation of beta-amyloid (Abeta) peptide. In addition, the neuronal and nonneuronal cholinergic systems have important roles in the modulation of regional cerebral blood flow. These findings may modify the overly simplistic cholinergic hypothesis in AD that is limited to symptomatic treatment and ignores the potential of cholinergic therapies as disease-modifying agents. Chronic increases in AChE activity may exacerbate neurodegenerative processes, make clinically relevant levels of AChE inhibition more difficult to achieve, and cause the therapeutic value of cholinesterase inhibitors (ChE-Is) to be limited and temporary. Rapidly reversible ChE-Is appear to increase AChE activity over the longer term whereas, remarkably, irreversible or very slowly reversible ChE-Is do not seem to have this effect. If such differences between ChE-Is are shown to have clinical correlates, this may prompt reconsideration of the rationale and expectations of some agents in the long-term management of AD.

Kivipelto M, Laakso MP, Tuomilehto J, Nissinen A, Soininen H. · Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland. · CNS Drugs. · Pubmed #12056919 No free full text.

Abstract: This paper focuses on hypertension and hypercholesterolaemia as risk factors for Alzheimer's disease and, as such, subjects for prevention. The long-term, prospective, population-based studies regarding the relationship between hypertension or hypercholesterolaemia and Alzheimer's disease, and the clinical studies regarding the association between antihypertensive or lipid-lowering medications and the risk of Alzheimer's disease, are reviewed. These studies provide evidence to suggest that elevated blood pressure and cholesterol levels earlier in life may have an important role in the development and expression of late-life Alzheimer's disease. Based on these data, we propose that proper, early interventions aimed at reducing these cardiovascular risk factors may have an impact on the future incidence and prevalence of Alzheimer's disease.

Rovio S, Kåreholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. · Aging Research Center, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm, Sweden. · Lancet Neurol. · Pubmed #16239176 No free full text.

Abstract: 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 Alzheimer's 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.

Pennanen C, Laakso MP, Kivipelto M, Ramberg J, Soininen H. · Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland. · J Neuroendocrinol. · Pubmed #14763994 No free full text.

Abstract: This study aimed to investigate whether there are differences in serum testosterone levels between male patients with Alzheimer's disease (AD) and cognitively normal male controls. Testosterone and sex hormone binding globulin (SHBG) levels were measured from 14 patients with mild to moderate AD and 16 age-matched control males. The AD patients had higher levels of serum total (P = 0.02) and free testosterone (P < 0.001), and higher free androgen index (FAI) (P = 0.02) compared to controls. No differences were found for the SHBG levels. These data provide no support for hypotheses of (disproportionally) decreased levels of serum testosterone in AD. These data also show that all cognitively normal controls had an FAI below the normal range.

Håkansson K, Rovio S, Helkala EL, Vilska AR, Winblad B, Soininen H, Nissinen A, Mohammed AH, Kivipelto M. · School of Social Sciences, Department of Psychology, Växjö University, Sweden. · BMJ. · Pubmed #19574312 links to  free full text

Abstract: OBJECTIVES: To evaluate whether mid-life marital status is related to cognitive function in later life. DESIGN: Prospective population based study with an average follow-up of 21 years. SETTING: Kuopio and Joensuu regions in eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. MAIN OUTCOME MEASURES: Alzheimer's disease and mild cognitive impairment. RESULTS: People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer's disease compared with married or cohabiting people. The highest increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. CONCLUSIONS: Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.

Solomon A, Kivipelto M. · Aging Research Center, Karolinska Institutet, Sweden. · Expert Rev Neurother. · Pubmed #19402779 No free full text.

Abstract: The link between cholesterol and Alzheimer's disease (AD) is indicated by genetic, epidemiological, experimental and clinical evidence, although the relationship is far from simple or straightforward. Compared with extracerebral cholesterol, little is known about brain cholesterol homeostasis. In addition, current diagnostic criteria for AD exclude a priori the pathogenic participation of vascular factors (to which cholesterol is traditionally associated), and require modifications. Randomized controlled trials suggest that the dementia stage of AD may already be too late for significant benefits of statin therapy, emphasizing the importance of early diagnosis and treatment. Cholesterol-modifying strategies may be more effective in dementia/AD prevention. Since cholesterol is only one piece of the dementia/AD puzzle, integrative interventions (lifestyle-related and, when necessary, pharmacologic) focusing on overall risk instead of individual risk factors may bring more benefit to individuals at risk.

Jauhiainen AM, Kangasmaa T, Rusanen M, Niskanen E, Tervo S, Kivipelto M, Vanninen RL, Kuikka JT, Soininen H. · Unit of Neurology, Institute of Clinical Medicine, Mediteknia, Kuopio, Finland. · Dement Geriatr Cogn Disord. · Pubmed #18987469 No free full text.

Abstract: 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.

Komulainen P, Pedersen M, Hänninen T, Bruunsgaard H, Lakka TA, Kivipelto M, Hassinen M, Rauramaa TH, Pedersen BK, Rauramaa R. · Kuopio Research Institute of Exercise Medicine, Finland. · Neurobiol Learn Mem. · Pubmed #18707012 No free full text.

Abstract: Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. While low circulating levels of BDNF have been suggested to predispose to Alzheimer's disease, very little data are available on its association with cognitive function in general population. We evaluated the association between plasma BDNF levels and cognition in a representative population sample of ageing men and women. The subjects (n=1389) were participants of the Dose-Responses to Exercise Training (DR's EXTRA) Study and represent a random sample of Eastern Finnish people (684 men and 705 women), 57-79 years of age at baseline of the study. Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery. Women had a higher mean (+/-SEM) plasma BDNF level than men (1721+/-55vs. 1495+/-54pg/ml, P<0.001). In women, 1 SD decrease in BDNF increased the risk for a low score in Naming Test by 53% (95% CI 1.21-1.92, P<0.001), in Mini-Mental State Examination by 63% (95% CI 1.21-2.20, P=0.001), in Word List Memory by 56% (95% CI 1.08-2.26, P=0.019), in Word List Recall by 50% (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99, P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data were adjusted for age, education, depression, impaired glucose metabolism, cardiovascular disease, antihypertensive medication, lipid lowering medication, use of sex hormones, smoking, alcohol consumption, storing time of plasma in the freezer and platelet count. BDNF was not associated with cognition in men. Present data suggest that plasma BDNF is a biomarker of impaired memory and general cognitive function in ageing women.

Tukiainen T, Tynkkynen T, Mäkinen VP, Jylänki P, Kangas A, Hokkanen J, Vehtari A, Gröhn O, Hallikainen M, Soininen H, Kivipelto M, Groop PH, Kaski K, Laatikainen R, Soininen P, Pirttilä T, Ala-Korpela M. · Computational Medicine Research Group, Department of Biomedical Engineering and Computational Science, Helsinki University of Technology, P.O. Box 9203, FI-02015 HUT, Finland. · Biochem Biophys Res Commun. · Pubmed #18700135 No free full text.

Abstract: A three-molecular-window approach for (1)H NMR spectroscopy of serum is presented to obtain specific molecular data on lipoproteins, various low-molecular-weight metabolites, and individual lipid molecules together with their degree of (poly)(un)saturation. The multiple data were analysed with self-organising maps, illustrating the strength of the approach as a holistic metabonomics framework in solely data-driven metabolic phenotyping. We studied 180 serum samples of which 30% were related to mild cognitive impairment (MCI), a neuropsychological diagnosis with severely increased risk for Alzheimer's disease (AD). The results underline the association between MCI and the metabolic syndrome (MetS). Additionally, the low relativeamount of omega-3 fatty acids appears more indicative of MCI than low serum omega-3 or polyunsaturated fatty acid concentration as such. The analyses also feature the role of elevated glycoproteins in the risk for AD, supporting the view that coexistence of inflammation and the MetS forms a high risk condition for cognitive decline.

Jones RW, Kivipelto M, Feldman H, Sparks L, Doody R, Waters DD, Hey-Hadavi J, Breazna A, Schindler RJ, Ramos H, Anonymous00217. · RICE (The Research Institute for the Care of Older People), Royal United Hospital, Bath, United Kingdom. · Alzheimers Dement. · Pubmed #18631958 No free full text.

Abstract: BACKGROUND: Growing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer's disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor's Effect in Alzheimer's Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily). METHODS: This is an international, multicenter, double-blind, randomized, parallel-group study with a double-blind randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental State Examination [MMSE] score, 13 to 25). Inclusion criteria included age 50 to 90 years, receiving donepezil 10 mg for at least 3 months before randomization, and low-density lipoprotein cholesterol levels (LDL-C) 2.5 to 3.5 mmol/L (95 to 195 mg/dL). Co-primary end points are changes in AD Assessment Scale-cognitive subscale (ADAS-cog) and AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale scores. A confirmatory end point is rate of change in whole brain and hippocampal volumes in patients who enrolled in the magnetic resonance imaging substudy. RESULTS: Enrollment of 641 subjects is complete. The baseline mean data are age 74 +/- 8 years, 53% women, MMSE 22 +/- 3, ADAS-cog 23 +/- 10, AD Functional Assessment and Change Scale (ADFACS) 13 +/- 9, Neuropsychiatric Inventory (NPI) 10 +/- 11, and Clinical Dementia Rating-Sum of Boxes (CDR-SB) 6 +/- 3. Mean prior donepezil treatment was 409 +/- 407 days. Mean baseline lipid levels are total cholesterol 5.8 +/- 0.8 mmol/L (224 +/- 33 mg/dL), LDL-C 3.7 +/- 0.7 mmol/L (143 +/- 26 mg/dL), triglycerides 1.5 +/- 0.7 mmol/L (132 +/- 64 mg/dL), and high-density lipoprotein cholesterol 1.6 +/- 0.5 mmol/L (64 +/- 18 mg/dL). CONCLUSIONS: LEADe will report in 2008 and is expected to provide a more definitive evaluation of the potential for statins in the treatment of people with AD.

Kivipelto M, Rovio S, Ngandu T, Kåreholt I, Eskelinen M, Winblad B, Hachinski V, Cedazo-Minguez A, Soininen H, Tuomilehto J, Nissinen A. · Aging Research Center, NVS, Karolinska Institutet, Stockholm, Sweden. · J Cell Mol Med. · Pubmed #18318693 No free full text.

Abstract: The risk of dementia and Alzheimer's 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 epsilon4 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 epsilon4 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]=1.61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE epsilon4 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 epsilon4 carriers. Composite effect of the lifestyle factors was particularly seen among the epsilon4 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 epsilon4 carriers. The apoE epsilon4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.

Ngandu T, von Strauss E, Helkala EL, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. · Aging Research Center, Karolinska Institutet, Gävlegatan 16, 11330 Stockholm, Sweden. · Neurology. · Pubmed #17909157 No free full text.

Abstract: 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.

Shafaati M, Solomon A, Kivipelto M, Björkhem I, Leoni V. · Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Neurosci Lett. · Pubmed #17822846 No free full text.

Abstract: Evidence was recently presented from in vitro studies that 24S-hydroxycholesterol acts as a signalling molecule inducing apoE-mediated cholesterol efflux from astrocytoma cells, and that there is a direct effect of the oxysterol on apoE transcription, protein synthesis and secretion. Consistent with this mechanism, a significant correlation is demonstrated here between levels of apoE and 24S-hydroxycholesterol in cerebrospinal fluid from patients with Alzheimer's disease and patients with mild cognitive impairment. Such a correlation was not found in control patients. There was no correlation between levels of apoE and cholesterol in cerebrospinal fluid from controls. The results are consistent with a close coupling between release of 24S-hydroxycholesterol and apoE secretion under conditions with neuronal degeneration. The levels of apoE in cerebrospinal fluid were also correlated to the levels of Tau and the possibility is discussed that the level of apoE in cerebrospinal fluid may be used as a marker of neurodegeneration.

Rovio S, Kåreholt I, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. · Aging Research Center, NVS, Karolinska Institutet, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #17721898 No free full text.

Abstract: BACKGROUND: Leisure-time physical activity has been related with a reduced risk of dementia and Alzheimer's disease (AD). The effects of occupational and commuting physical activity (physical activity at work and on the way to work) on cognitive health are still unclear. This study aimed to clarify the association between work-related physical activity and dementia/AD. METHODS: Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years participated in the re-examination in 1998. RESULTS: Neither occupational [Odds Ratio (OR) 1.45; 95% Confidence Intervals (CI) 0.66-3.17] nor commuting physical activity (OR 0.46; 95% CI 0.10-2.17) were associated with the risk of dementia or AD after adjustments for age, sex, education, follow-up time, locomotor symptoms, main occupation during life, income at midlife, leisure-time physical activity, other subtype of work-related physical activity, ApoE genotype, vascular disorders and the smoking status. There were also no interactions between work-related physical activity and the ApoE epsilon4 genotype, leisure-time physical activity or sex. CONCLUSIONS: In this study, work-related physical activity was not found to be sufficient to protect against dementia and AD later in life. The lack of effect might be partly due to a residual confounding. Nevertheless, physical activity during leisure-time may be beneficial even for people who are physically active at work or when commuting.

Solomon A, Kåreholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. · Department of Neuroscience and Neurology, University of Kuopio, Finland. · Neurology. · Pubmed #17339582 No free full text.

Abstract: BACKGROUND: Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear. OBJECTIVE: To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition. METHODS: Participants of the Cardiovascular Risk Factors, Aging and Dementia 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 aged 65 to 79 were reexamined in 1998. RESULTS: Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment. CONCLUSIONS: The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment.

Aguero-Torres H, Kivipelto M, von Strauss E. · Aging Research Center (ARC), Karolinska Institutet, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #16902279 No free full text.

Abstract: OBJECTIVE: To explore the hypothesis that older adults often are affected by more than one disease, making the differential diagnosis between Alzheimer's disease (AD) and vascular dementia (VaD) difficult. METHODS: Incident dementia cases (n = 308) from a population-based longitudinal study of people 75+ years were investigated. The DSM-III-R criteria were used for the clinical diagnosis of dementia. Data on vascular disorders (hypertension, cerebrovascular and ischemic heart diseases, heart failure, atrial fibrillation, diabetes) as well as type of onset/course of dementia were used retrospectively to reclassify dementias. RESULTS: Only 47% of the AD cases were reclassified as pure AD without any vascular disorder. Among subjects with AD and with a vascular component, cerebrovascular disease was the most common (41%). Only 25% of VaD were reclassified as pure VaD. Further, 26% of the pure AD subjects developed a vascular disorder in the following 3 years. CONCLUSIONS: Both vascular and degenerative mechanisms may often contribute to the expression of dementia among the elderly. Most of the AD cases have vascular involvements, and pure dementia types in very old subjects constitute only a minority of dementia cases.

Kivipelto M, Solomon A, Winblad B. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866921 No free full text.

This publication has no abstract.

Kivipelto M, Solomon A, Blennow K, Olsson AG, Winblad B. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866903 No free full text.

This publication has no abstract.

Laitinen MH, Ngandu T, Rovio S, Helkala EL, Uusitalo U, Viitanen M, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. · Aging Research Center, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #16710090 No free full text.

Abstract: 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 epsilon4 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 epsilon4 carriers. Thus, dietary interventions may potentially modify the risk of dementia, particularly among genetically susceptible individuals.

Leoni V, Shafaati M, Salomon A, Kivipelto M, Björkhem I, Wahlund LO. · Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital in Huddinge, Stockholm, Sweden. · Neurosci Lett. · Pubmed #16406316 No free full text.

Abstract: There is a need for effective biomarkers showing whether or not a patient with mild cognitive impairment (MCI) will progress to Alzheimer's disease (AD) with dementia. At the present three cerebrospinal fluid (CSF) biomarkers are in general use: total tau, phospho-tau and beta-Amyloid. These markers are regarded to have high capacity to differentiate early AD from normal ageing. We have analysed CSF levels of a new marker for neuronal degeneration, 24S-hydroxycholesterol (24OHC) in patients with MCI. For reasons of comparison, we also analysed these levels in patients with AD. There was a significant correlation between CSF levels of 24OHC and total tau (as well as phospho-tau) in both groups of patients. Fifty percent of the patients contemplated for MCI were found to have elevated levels of 24OHC (using a 95th upper percentile set cut-off). All the MCI patients with normal levels of 24OHC had normal levels of the other markers. In patients with AD, the percentages of those with increased levels of 24OHC, tau and phospho tau were similar (55-67%). In this pilot study, we discuss the possibility that 24OHC may be a sensitive test for MCI.