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Biomedical subjects

M Kivipelto

Publications and source records attributed to M Kivipelto.

17 recordsLinked to original sources
PubMed2006

Body mass index and the risk of Parkinson disease.

OBJECTIVE: To examine the association between body mass index (BMI) and the risk of Parkinson disease (PD). METHODS: Study cohorts included 22,367 Finnish men and 23,439 women 25 to 59 years of age without a history of PD at baseline. Hazards ratios (HRs) of incident PD were estimated for different levels of BMI. RESULTS: During a mean follow-up period of 18.8 years, 272 men and 254 women developed incident PD. After adjustment for confounding factors (age, study years, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, and alcohol, coffee, and tea consumption), the HRs of PD at different levels of BMI (<23, 23 to 24.9, 25 to 26.9, 27 to 29.9, and > or =30 kg/m(2)) were 1.00, 1.97 (95% CI: 1.21 to 3.22), 1.83 (95% CI: 1.12 to 2.99), 2.34 (95% CI: 1.45 to 3.78), and 2.44 (95% CI: 1.44 to 4.15) in men, and 1.00, 1.50 (95% CI: 0.95 to 2.37), 1.65 (95% CI: 1.05 to 2.59), 1.79 (95% CI: 1.15 to 2.80), and 1.77 (95% CI: 1.12 to 2.78) in women, and 1.00, 1.70 (95% CI: 1.23 to 2.37), 1.70 (95% CI: 1.23 to 2.37), 2.02 (95% CI: 1.46 to 2.79), and 2.03 (95% CI: 1.44 to 2.85) in men and women combined (adjusted also for sex). In both sexes combined, the multivariate-adjusted direct association between BMI and the risk of PD was present both in subjects aged 25 to 49 years and 50 to 59 years, in never smokers and smokers and in participants diagnosed PD before and after 65 years of age. CONCLUSION: Body mass index is associated with a risk of Parkinson disease. The effect is graded and independent of other risk factors.

Adult↗
PubMed2006

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 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.

Aged↗
PubMed2006

Cholesterol as a risk factor for Alzheimer's disease - epidemiological evidence.

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.

Age Factors↗
PubMed2005

Clinical trials in mild cognitive impairment: lessons for the future.

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.

Aged↗
PubMed2005

A voxel based morphometry study on mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.

Aged↗
PubMed2004

Serum testosterone levels in males with Alzheimer's disease.

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.

Aged↗
PubMed2004

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Aged↗
PubMed2004

Risk and protective effects of the APOE gene towards Alzheimer's disease in the Kungsholmen project: variation by age and sex.

BACKGROUND: The risk effect of APOE epsilon 4 allele for Alzheimer's disease is acknowledged, whereas the putative protective effect of epsilon 2 allele remains in debate. OBJECTIVES: To investigate whether those inconsistent findings may be attributable to differences in age and sex composition of the study populations. METHODS: A community dementia free cohort (n = 985) aged > or =75 years was followed up to detect Alzheimer's disease cases (DSM-III-R criteria). Data were analysed using Cox models with adjustment for major potential confounders. RESULTS: Over a median 5.6 year follow up, Alzheimer's disease was diagnosed in 206 subjects. Compared with APOE epsilon 3/epsilon 3 genotype, the relative risk (RR) of Alzheimer's disease was 1.4 (95% confidence interval (CI), 1.0 to 2.0; p = 0.03) for heterozygous epsilon 4 allele and 3.1 (95% CI, 1.6 to 5.9) for homozygous epsilon 4 allele. The association between epsilon 4 allele and Alzheimer's disease risk was stronger in men than in women (RR related to the interaction term epsilon 4 allele by sex, 0.4; 95% CI, 0.2 to 0.9). The epsilon 4 allele accounted for one third of Alzheimer's disease cases among men, but only one tenth among women. The epsilon 2 allele was related to a reduced Alzheimer's disease risk mainly in people aged <85 years (RR, 0.4; 95% CI, 0.2 to 0.8). The RR of Alzheimer's disease related to the interaction term of epsilon 2 allele by age was 2.4 (95% CI, 1.0 to 6.0; p = 0.06). CONCLUSIONS: The APOE genotype specific effects on Alzheimer's disease vary by age and sex, in which the epsilon 4 allele has a stronger risk effect in men, and the epsilon 2 allele confers a protective effect only in younger-old people.

Age Factors↗
PubMed2003

Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers.

Apolipoprotein E (ApoE) genotype has been shown to influence results in neuroimaging studies using a number of various imaging modalities. No in vivo data exists on whether or not there are ApoE-related changes observable by proton magnetic resonance spectroscopy (MRS). In this study we measured absolute peak areas of proton MR spectra obtained from the occipital cortex in 22 non-demented elderly with (n = 8) or without (n = 14) the ApoE epsilon4 allele. No statistically significant differences were found in levels of N-acetyl aspartate, myo-inositol, or choline containing compounds between the groups. Instead, compared with the non-carriers, the levels of creatine were significantly lower in the epsilon4 carriers, suggesting increased metabolic demands in the brain of the epsilon4 carriers. The levels of creatine also correlated significantly with age and performance on the Mini-Mental State Examination test in the epsilon4 carriers, but not in the non-carriers. These findings may be of significant clinical interest as potential indicator of incipient AD, and also from therapeutical point of view given the potential neuroprotective effects of creatine.

Aged↗
PubMed2002

Midlife income, occupation, APOE status, and dementia: a population-based study.

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.

Aged↗
PubMed2002

Usefulness of repeated presentation of Mini-Mental State Examination as a diagnostic procedure--a population-based study.

MATERIAL AND METHODS: The 280 subjects who achieved 24 points or less in the Mini-Mental State Examination (MMSE) in the first survey of 1449 subjects were invited for a comprehensive diagnostic examination for dementia including medical history, thorough neurological and cardiovascular examinations and detailed neuropsychological evaluation, magnetic resonance imaging (MRI)-study, cerebrospinal fluid (CSF)-analysis, electrocardiogram (ECG), chest radiograph and blood tests after the first assessment. The MMSE was presented again. RESULTS: Out of 240 persons, 57 subjects were diagnosed as having dementia. When the cut-off point of 24 or less in the second MMSE was used, the sensitivity of the second MMSE was 82% and the specificity was 64%. The positive predictive value of the second MMSE was 42% and negative predictive value 92%. The non-demented subjects improved their MMSE score at the second examination. In contrast, the demented subjects maintained their low MMSE score at the second examination.

Aged↗
PubMed2001

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.

OBJECTIVE: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. BACKGROUND: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. RESULTS: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. CONCLUSION: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

Aged↗
PubMed2001

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study.

OBJECTIVE: To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer's disease in later life. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998. MAIN OUTCOME MEASURES: Midlife blood pressure and cholesterol concentrations and development of Alzheimer's disease in later life. RESULTS: People with raised systolic blood pressure (>/=160 mm Hg) or high serum cholesterol concentration (>/=6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer's disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer's disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer's disease. CONCLUSION: Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer's disease in later life.

Adult↗
PubMed2001

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

Aged↗
PubMed1996

Depletion of serotonin, dopamine and noradrenaline in aged rats decreases the therapeutic effect of nicotine, but not of tetrahydroaminoacridine.

The present study investigates the effects of nicotine (0.1 and 0.3 mg/kg) and tetrahydroaminoacridine (3 mg/kg) treatment on spatial navigation in aged control and p-chlorophenylalanine (a serotonin (5-hydroxytryptamine, 5-HT) synthesis inhibitor, 400 mg/kg on 3 successive days, i.p.)-treated rats. p-Chlorophenylalanine did not aggravate the water maze failure of aged rats. Nicotine (0.3 mg/kg) was more effective than tetrahydroaminoacridine (3 mg/kg) in promoting water maze navigation by aged control rats. p-Chlorophenylalanine blocked the therapeutic effect of nicotine (0.3 mg/kg),but did not decrease the effect of tetrahydroaminoacridine (3 mg/kg) in aged rats. Frontal cortex dopamine levels and choline acetyltransferase activity were lower in aged rats, but 5-HT and noradrenaline levels were unaltered. p-Chlorophenylalanine decreased selectively 5-HT levels in young rats, but in aged rats 5-HT, dopamine and noradrenaline levels were decreased. These results suggest that aged rats are neurochemically more sensitive to p-chlorophenylalanine treatment and that tetrahydroaminoacridine may more effectively than nicotine stimulate spatial learning if 5-HT, dopamine and noradrenaline systems are severely affected.

Aging↗