PubMed Health⌕ Search

Biomedical subjects

L Fratiglioni

Publications and source records attributed to L Fratiglioni.

At least 19 recordsLinked to original sources
PubMed2004

Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study.

BACKGROUND: Research on diabetes mellitus as a risk factor for dementia and its main subtypes has produced conflicting results. The authors investigated the relationship between diabetes mellitus and risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: A dementia-free cohort of 1,301 community dwellers aged 75 years and older in Stockholm, Sweden, was longitudinally examined twice over 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders-III-R diagnostic criteria). Cox proportional hazards models were used to analyze the data with adjustment for several potential confounders. RESULTS: During the 5,584 person-years of follow-up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p = 0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1) for AD. Patients who were treated with oral antidiabetic medications had HRs of 1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for VaD. There were significant interactions of diabetes with severe systolic hypertension (> or =180 mm Hg) on dementia and its main subtypes, and of diabetes with heart disease on VaD. CONCLUSIONS: Diabetes mellitus increases the risk of dementia, and VaD in particular, in very old people. The risk for dementia and VaD is especially high when diabetes mellitus occurs together with severe systolic hypertension or heart disease.

Aged↗
PubMed2004

APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging.

OBJECTIVE: To investigate whether presence of the APOE epsilon4 allele is related to the pathologic progression of preclinical Alzheimer disease (AD), as reflected by change in Mini-Mental State Examination (MMSE) scores among persons in the preclinical phase of AD, and cognitively intact adults confirmed as dementia-free during the 6-year assessment period. METHOD: In a population-based sample, participants were stratified according to APOE genotype (epsilon4 or non-epsilon4) and whether they received a diagnosis of AD at the end of either a 3- or 6-year assessment period. Participants were aged 75 years and older, and were nondemented at baseline. At the end of the 3-year period, 17.2% of non-epsilon4 and 26.7% of epsilon4 carriers became demented. For the 6-year period those percentages were 11.2% for non-epsilon4 carriers and 16.9% for epsilon4-carriers. RESULTS: Individuals in the preclinical phase of AD showed greater decline on the MMSE as compared to nondemented adults. However, the decline was most marked in the 3 years prior to clinical diagnosis. Further, APOE-epsilon4 genotype did not modify the rate of decline among to-be-demented participants, as well as individuals who would remain free of AD. CONCLUSIONS: Although possession of the APOE epsilon4 allele is a risk factor for AD in old age, it does not modify the progression of the disease during the preclinical period. Further, in the absence of preclinical dementia, APOE did not influence global cognitive change in nondemented persons.

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↗
PubMed2002

Predictors of cognitive change from preclinical to clinical Alzheimer's disease.

We examined individual-difference variables in relation to the rate of change in global cognitive performance, measured by the MMSE, from 3 years prior to diagnosis of Alzheimer's disease (AD) to the time of diagnosis. The population-based sample consisted of 230 incident AD persons who were followed over a 3-year interval. The average annual decline in MMSE was 1.81 points. Being older and acquiring additional diseases during the 3 years preceding diagnosis predicted a faster rate of decline in global cognitive functioning. However, other individual difference variables such as sex, education, depression, vitamin levels (vitamin B12 and folic acid), apolipoprotein status, and social network did not precipitate the rate of decline in the preclinical phase of AD.

Aged↗
PubMed2001

Vitamin B(12) and folate in relation to the development of Alzheimer's disease.

OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. METHODS: A population-based longitudinal study in Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.

Aged↗
PubMed2001

[Epidemiology of aging with focus on physical and mental functional ability].

In the past decades, the "graying" of the population has emerged as a world-wide phenomenon, leading to an increased interest in research on aging. Many population-based studies have been initiated in several countries, such as the Kungsholmen Project in Stockholm, Sweden. These studies have shown that older adults can be recruited to participate in intensive physiological and clinical evaluations, and that longitudinal surveys are well accepted by the elderly. Comorbidity and physical and mental functioning have emerged as important variables for describing health status and identifying risk factors. Dementia arose as one of the most common diseases in the very old, as dementia prevalence nearly doubles every fifth year. Some risk factors for Alzheimer's disease have been identified and interesting working hypotheses have been suggested. The natural history of the dementias have been sufficiently outlined for allocating medical and social resources, and for counseling patients and relatives.

Activities of Daily Living↗
PubMed2001

Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: variation by use of antihypertensive medication?

The authors examined the impact of the apolipoprotein E (APOE)(*)epsilon4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged >/=75 years was followed for an average of 3 years (1990-1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with (*)epsilon3/(*)epsilon3, the APOE(*)epsilon4 allele increased the risk of developing dementia (relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1) and Alzheimer's disease (RR = 1.7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among (*)epsilon4 carriers. For those not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (95% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE(*)epsilon4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.

Age Factors↗
PubMed2001

The influence of education on clinically diagnosed dementia incidence and mortality data from the Kungsholmen Project.

BACKGROUND: The relationship between education and Alzheimer disease (AD) or dementia has been widely examined and the evidence obtained is mixed. Several hypotheses have been proposed to explain the observed association between them. OBJECTIVE: To further understand the relationship between education and incidence of clinically diagnosed AD or dementia. SUBJECTS AND METHODS: A community-based, dementia-free cohort of 1296 aged 75 years and older was followed up to detect incident AD or dementia cases using Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria. The vital status of all subjects who underwent the clinical examination at follow-up (n = 983) was ascertained for 5 years further. Data were analyzed with Cox proportional hazards model after adjustment for main potential confounders. RESULTS: Over an average (SD) of 2.8 (1.0) years of follow-up, 147 subjects were diagnosed as having dementia (109 subjects as having AD). Among those who were clinically examined at follow-up, 88 died with dementia (68 died with AD) within 5 years. Subjects with a low level of education (<8 vs > or =8 years) had a relative risk of 2.6 (95% confidence interval, 1.5-4.4) for AD and 1.7 (95% confidence interval, 1.1-2.6) for dementia. A low educational level was significantly related to all-cause mortality (relative risk, 1.3; 95% confidence interval, 1.0-1.7; P<.05), but not to the mortality of subjects with AD (relative risk, 1.1; 95% confidence interval, 0.5-2.2) or dementia (relative risk, 0.9; 95% confidence interval, 0.5-1.5). CONCLUSIONS: A low level of education is related to an increased incidence of clinical AD or dementia, but not to the mortality of subjects with AD or dementia. These findings can be accounted for by the "cognitive reserve" hypothesis. Alternatively, the observed association between educational level and incidence of AD or dementia may partly reflect detection bias, by which subjects with a low level of education tend to be clinically diagnosed at an earlier point in time.

Aged↗
PubMed2001

Institutionalization in the elderly: the role of chronic diseases and dementia. Cross-sectional and longitudinal data from a population-based study.

A population-based study of 1810 persons, aged 75+, was investigated to evaluate the role of dementia and other chronic diseases as determinants of institutionalization in the elderly. The study population was examined at baseline and after a 3-year interval. After adjustment for sociodemographic characteristics, functional dependence, dementia, cerebrovascular disease and hip fracture were associated with living in an institution at baseline. Additionally, functional dependence, hip fracture and dementia were also associated with moving to an institution during the 3-year follow-up. In a similar analysis, including only nondemented subjects, the Mini-Mental State Examination emerged as one of the strongest determinants. The population attributable risk percentage of institutionalization during the 3-year follow-up due to dementia was 61%. This study confirms that dementia and cognitive impairment are the main contributors to institutionalization in the elderly, independently of their sociodemographic status, social network, or functional status.

Age Distribution↗
PubMed2001

Stability of the preclinical episodic memory deficit in Alzheimer's disease.

We sought to determine the course of the preclinical episodic memory deficit in Alzheimer's disease. Using data from a population-based study, we compared persons who developed Alzheimer's disease n = 15) with persons who were non-demented n = 105) 6 and 3 years prior to the diagnosis of dementia. Participants were tested on tasks assessing episodic memory free recall and recognition of words) and short-term memory digit span). The incident Alzheimer's disease cases performed more poorly than their non-demented counterparts both 3 and 6 years before diagnosis on recall and recognition. There were no group differences in either forward or backward digit span. The selective impairment of episodic memory before the diagnosis of Alzheimer's disease is consistent with the view that early changes in the hippocampal complex play an important role in the memory deficit in preclinical Alzheimer's disease. On both preclinical measurement occasions, recall and recognition made independent contributions to group classification in logistic regression analyses. However, there was no evidence for accelerated decline of episodic memory in the incident Alzheimer's disease group from 6 to 3 years before diagnosis. These results indicate that Alzheimer's disease is characterized by a long preclinical period during which episodic memory deficits are detectable. The magnitude of these deficits appears to be quite stable, at least up to 3 years before diagnosis. This may reflect the fact that those biological events that eventually result in clinically diagnosed Alzheimer's disease e.g. the appearance of amyloid plaques and neurofibrillary tangles) accumulate at a relatively slow rate.

Aged↗
PubMed2000

Incidence of stroke in relation to cognitive function and dementia in the Kungsholmen Project.

OBJECTIVE: To investigate whether cognitive function is related to incidence of stroke. METHODS: A population-based cohort of 1551 subjects with no clinical history or signs of stroke, age 75 years and over at baseline, were followed up for 3 years. Individuals with a first-ever stroke event that was recorded in the Stockholm inpatient register after the date of baseline interview were considered as incident stroke patients. Diagnosis of stroke followed the International Classification of Disease, 9th Revision (ICD-9). Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised (DSM-III-R). Cognitive functioning was assessed with the Mini-Mental State Examination. RESULTS: During the 4102 person-years of follow-up, 110 events were recorded, giving an overall incidence of stroke of 26.8 per 1000 person-years. Subjects with mild dementia had a relative risk of 2.6 (95% CI, 1.2 to 5.7) of developing stroke after controlling for the potential confounders. The corresponding figure for subjects with cognitive impairment was 2.0 (95% CI, 1.0 to 3.8; p = 0.05). There was a tendency for subjects who developed stroke to be more likely to have vascular factors (systolic blood pressure >180 mm Hg, heart disease, or diabetes mellitus) than those who did not. CONCLUSIONS: Mild dementia and cognitive impairment are associated with an increased incidence of stroke among subjects age 75 years old and over. Because stroke increases risk of dementia and prior stroke increases risk of a subsequent stroke, mild dementia and cognitive impairment may be a manifestation of clinically unrecognized stroke.

Aged↗
PubMed2000

Influence of social network on occurrence of dementia: a community-based longitudinal study.

BACKGROUND: Few data are available on the effect of social ties on dementia development. This study explored whether single social network components and different degrees of the social connections affect dementia incidence. METHODS: A community-based cohort of 1203 non-demented people, living at home in the Kungsholmen district of Stockholm, Sweden, and who had good cognition, was followed for an average period of 3 years. On the basis of medical and psychological data, 176 patients were diagnosed with dementia according to the criteria of the third edition revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on social network was obtained by personal interview by trained nurses at baseline. The covariates included in the analysis were age, sex, education, cognitive and functional status, depressive symptoms, and vascular diseases. FINDINGS: Those individuals living alone, and those without any close social ties, both had an adjusted relative risk for developing dementia of 1.5 (95% CI 1.0-2.1 and 1.0-2.4, respectively). Compared with married people living with someone, single people and those living alone had an adjusted relative risk of 1.9 (95% CI 1.2-3.1). Infrequent contacts with network resources did not increase the risk of the disease if such contacts were experienced as satisfying. When all components were combined in an index, a poor or limited social network increased the risk of dementia by 60% (95% CI 1.2-2.1), and a significant gradient was found for the four degrees of social connections (p=0.0009). INTERPRETATION: An extensive social network seems to protect against dementia. Confirmation of this finding and further investigation to clarify the mechanisms are worthwhile due to the implications for prevention.

Aged↗
PubMed2000

The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample.

OBJECTIVES: To examine the ability of the total score and individual items from the Mini-Mental State Examination in predicting the development of Alzheimer disease (AD) across a 3- and 6-year period in a population-based sample, and to describe the longitudinal changes in these measures across the same follow-up periods. DESIGN: Prospective follow-up of a community-based cohort, with 3 times of testing across a 6-year period. At each time of measurement, participants were clinically examined by physicians to identify demented and nondemented participants according to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria. PARTICIPANTS: The study population consisted of all participants who were nondemented at the first follow-up and participated in the second follow-up examination. Among those, 459 remained nondemented and 73 developed AD during the second follow-up period. RESULTS: Baseline differences in the total Mini-Mental State Examination score and the delayed memory item were seen 6 years before eventual dementia diagnosis (P<.01). Analysis of the longitudinal changes showed no differences in the rate of decline for the incident AD or nondemented group between time 1 and time 2 (P>.10). However, the incident AD group exhibited precipitous declines in 8 of the 10 subscales between time 2 and time 3, the point at which they were clinically diagnosed (P<.01). Logistic regression analyses showed that only the delayed memory item was a significant predictor of who would develop AD, independent of age, sex, and years of education, at both of the first 2 times of measurement (P<.001). CONCLUSIONS: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered. Arch Neurol. 2000.

Aged↗
PubMed2000

Lead concentrations in elderly urban people related to blood pressure and mental performance: results from a population-based study.

BACKGROUND: The Kungsholmen project is a longitudinal study of ageing and dementia conducted in Stockholm in 1987. In a 1994-96 follow-up, 804 subjects had their blood samples analyzed for lead. METHODS: Lead concentration in blood in an elderly population aged 75+ (mean age of 88.4 years) was studied in relation to age, blood pressure (BP), body mass index (BMI), cognitive function measured with Mini-Mental State Examination (MMSE), gender, and smoking. RESULTS: The mean blood lead level (n = 762) was 3.7 microg/dL (0.18 micromol/L) whole blood with a standard deviation of 2.3, (0.11). There was a contribution of gender with men having higher blood lead levels than women (beta = -0.20; P = 0.000001) but not of smoking habits (beta = 0.07; P = 0.08) when these variables were entered into a multiple regression model with lead as the dependent variable (R = 0.22; P < 0.000001). Different multiple regression models were tested with lead as the dependent variable. No relation was found between lead concentrations and age, BMI, systolic BP, diastolic BP, or MMSE. Systolic and diastolic BP were correlated to BMI (R = 0.10; P = 0.01 and R = 0.22; P = 0.000 001, respectively). CONCLUSIONS: In this elderly population from a specified area of Stockholm it is unlikely that lead exposure affects BP or cognition. However, high lead levels in blood may reflect earlier occupational exposure or life style factors.

Age Factors↗
PubMed2000

Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies.

The relationship between smoking and neurological diseases has always been controversial. Even the expected association between smoking and increased risk for cerebrovascular disease has been debated for years. It was at the end of the 1980s that smoking became definitively accepted as a risk factor for ischemic stroke. More recently, two other neurological diseases have been studied in relation to smoking: Parkinson's disease (PD) and Alzheimer's disease (AD). Many epidemiological studies have found a highly significant negative association between cigarette smoking and these two neurodegenerative disorders. The risk of AD or PD in nonsmokers has generally been about twice that of smokers. That is, patients with AD or PD are approximately 50% less likely to have smoked cigarettes during their lifetime than are age- and gender-matched controls. Alternatively, cigarette smokers are 50% less likely to have PD or AD than are age- and gender-matched nonsmokers. This statistically significant negative association has been interpreted as suggesting that cigarette smoking exerts an undefined, biologic, neuroprotective influence against the development of PD and AD. A review of all studies that either support or refute this hypothesis is presented separately for PD and AD.

Alzheimer Disease↗