Alzheimer Disease: Fratiglioni L

Winblad B, Wimo A, Möbius HJ, Fox JM, Fratiglioni L. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #10556861 No free full text.

This publication has no abstract.

Fratiglioni L, Winblad B, von Strauss E. · Karolinska Institutet, Aging Research Center, Division of Geriatric Epidemiology, NVS, and Stockholm Gerontology Research Center, Gävlegatan 16, S-113 30 Stockholm, Sweden. · Physiol Behav. · Pubmed #17588621 No free full text.

Abstract: The aging of the population is a worldwide phenomenon, and studying age-related diseases has become a relevant issue from both a scientific and a public health perspective. This review summarises the major findings concerning prevention of Alzheimer's disease (AD) and other dementias from a population-based study, the Kungsholmen Project. The study addresses risk- and protective factors for AD and dementia from a lifetime perspective: at birth, during childhood, in adult life, and in old age. Although many aspects of the dementias are still unclear, some risk factors have been identified and interesting hypotheses have been suggested for other putative risk or protective factors. At the moment it is also possible to delineate some preventative strategies for dementia.

Qiu C, De Ronchi D, Fratiglioni L. · Aging Research Center, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet and the Stockholm Gerontology Research Center, Stockholm, Sweden. · Curr Opin Psychiatry. · Pubmed #17551353 No free full text.

Abstract: PURPOSE OF REVIEW: The epidemiology of dementia is one of the priority fields in aging research. This review aims to highlight the most relevant findings over last years concerning occurrence, risk factors, and prevention of dementia and its major subtypes. RECENT FINDINGS: It is estimated that currently around 24 million people have dementia in the world, with the number being projected to double every 20 years, and that 60% of dementia patients live in developing countries, with the proportion being raised to more than 70% by 2040. Current evidence suggests that vascular factors, such as midlife hypertension, diabetes, and cerebrovascular disease, contribute significantly to the development of dementia and Alzheimer's disease, and that active engagement in mental, physical, and social activities may postpone the onset of dementia by providing cognitive reserve. SUMMARY: Dementia represents a major public health challenge as a consequence of rapid increase in the aging population worldwide, especially in developing countries. This challenge can be partly confronted by successful development of preventive strategies. Evidence has emerged that proper control of vascular disorders and maintenance of active lifestyles may prevent or delay the onset and progression of dementia and Alzheimer's disease. Intervention trials are warranted to determine, to what extent, such programs are effective against dementia.

Qiu C, Winblad B, Fratiglioni L. · Aging Research Centre, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institute and Stockholm Gerontology Research Centre, Stockholm, Sweden. · Lancet Neurol. · Pubmed #16033691 No free full text.

Abstract: The relation of blood pressure with cognitive function and dementia has, in recent years, received much attention from epidemiological research. Some cross-sectional studies have shown an inverse association between blood pressure and the prevalence of dementia and Alzheimer's disease, whereas longitudinal studies yield mixed results that largely depend on the age at which blood pressure is measured and the time interval between blood pressure and outcome assessments. Some studies suggest that midlife high blood pressure is a risk factor for late-life cognitive impairment and dementia, and that low diastolic pressure and very high systolic pressure in older adults may be associated with subsequent development of dementia and Alzheimer's disease. Observational studies and randomised clinical trials provide limited evidence for a protective effect of antihypertensive therapy against dementia and stroke-related cognitive decline. Atherosclerosis resulting from long-standing hypertension, and cerebral hypoperfusion secondary to severe atherosclerosis and to low blood pressure may be major biological pathways linking both high blood pressure in midlife and low blood pressure in late-life to cognitive decline and dementia.

Fratiglioni L, Paillard-Borg S, Winblad B. · Aging Research Center, Division of Geriatric Epidemiology and Medicine, Neurotec Department, Karolinska Institute and Stockholm Gerontology Research Center, Stockholm, Sweden. · Lancet Neurol. · Pubmed #15157849 No free full text.

Abstract: The recent availability of longitudinal data on the possible association of different lifestyles with dementia and Alzheimer's disease (AD) allow some preliminary conclusions on this topic. This review systematically analyses the published longitudinal studies exploring the effect of social network, physical leisure, and non-physical activity on cognition and dementia and then summarises the current evidence taking into account the limitations of the studies and the biological plausibility. For all three lifestyle components (social, mental, and physical), a beneficial effect on cognition and a protective effect against dementia are suggested. The three components seem to have common pathways, rather than specific mechanisms, which might converge within three major aetiological hypotheses for dementia and AD: the cognitive reserve hypothesis, the vascular hypothesis, and the stress hypothesis. Taking into account the accumulated evidence and the biological plausibility of these hypotheses, we conclude that an active and socially integrated lifestyle in late life protects against dementia and AD. Further research is necessary to better define the mechanisms of these associations and better delineate preventive and therapeutic strategies.

Fratiglioni L, Wang HX. · Stockholm Gerontology Research Center, NEUROTEC, Karolinska Institute, Huddinge University Hospital, Sweden. · Behav Brain Res. · Pubmed #10942038 No free full text.

Abstract: 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.

Agüero-Torres H, Winblad B, Fratiglioni L. · Stockholm Gerontology Research Center, The Kungsholmen Project, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #10609677 No free full text.

Abstract: Vascular dementia, the second most common dementia after Alzheimer disease, has great potential for prevention and treatment. Epidemiological data provide the basis for planning primary prevention and clinical trials. Nevertheless, general consensus on disease definition and diagnostic criteria are still not well defined. Despite these limitations, some results from the Kungsholmen project, an epidemiological longitudinal study of people 75 years and older, are presented here.

Berger AK, Fratiglioni L, Winblad B, Bäckman L. · Aging Research Center--ARC, Division of Geriatric Epidemiology, NEUROTEC, Karolinska Institute, Stockholm. · Cortex. · Pubmed #16042036 No free full text.

Abstract: Both Alzheimer's disease (AD) and depression (D) are prevalent disorders in old age and may co-occur in the same individual. The present study examined whether a diagnosis of D in AD has negative effects on cognitive functioning in the preclinical stage of the diseases, as well as at the time when the diagnoses were rendered. Population-based samples of 13 individuals with incident AD and D, 109 incident AD cases without D, and 179 normal older adults were followed over a three-year period. The groups were compared preclinically and at the time of diagnosis on global cognitive functioning using the MMSE total and the specific item scores, as well as the occurrence of depressive symptoms. As expected, there were clear AD-related deficits preclinically, which were exacerbated at follow-up. In addition, there were D-related deficits on three MMSE items (i.e., following commands, reading, and writing). The poorer performance on the three MMSE items was linked to an elevation of depressive symptoms. However, D was not associated with greater decline in cognitive functioning over the three-year follow-up period. Thus, although depressive symptoms may result in slight cognitive deficits in preclinical AD, at the time of the dementia diagnosis these effects may be absorbed by the neurodegenerative process.

Jones S, Small BJ, Fratiglioni L, Backman L. · No affiliation provided · Brain Cogn. · Pubmed #15259392 No free full text.

Abstract: 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.

Small BJ, Fratiglioni L, Viitanen M, Winblad B, Bäckman L. · Department of Gerontology, Mailbox SOC 107, University of South Florida, 4202 E Fowler Ave, Tampa, FL 33620, USA. · Arch Neurol. · Pubmed #10867781 links to  free full text

Abstract: 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.

Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. · Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. · Diabetes. · Pubmed #18952836 links to  free full text

Abstract: OBJECTIVE: We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association. RESEARCH DESIGN AND METHODS: This study included 13,693 twin individuals aged > or =65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression. RESULTS: Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16-2.36) for Alzheimer's disease, and 2.17 (1.36-3.47) for vascular dementia. Compared with late-life diabetes (onset age > or =65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30-1.53) for dementia related to mid- and late-life diabetes, respectively. CONCLUSIONS: Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association but could not account for the mid-life diabetes-dementia association.

Fratiglioni L, Qiu C. · Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm Gerontology Research Center, Gavlegatan 16, S-113 30, Stockholm, Sweden. · Exp Gerontol. · Pubmed #18620039 No free full text.

Abstract: Since population aging has become a worldwide phenomenon, the burden of the age-related neurodegenerative diseases is expected to increase dramatically in both developed and developing nations. Alzheimer's disease is the most common neurodegenerative disorder among old people. Prevention may represent an ideal solution to the challenge posed by this condition. Recent epidemiological studies have revealed a number of risk and protective factors that could influence occurrence of dementia including Alzheimer type dementia. We propose that an active and stimulating lifestyle in late life as well as an optimal control of vascular and other chronic diseases both at middle age and late life can be two possible intervention strategies to prevent or postpone the onset of dementia, and perhaps other neurodegenerative disorders such as Parkinson's disease.

Palmer K, Bäckman L, Winblad B, Fratiglioni L. · Aging Research Center, Karolinska Institutet, and Stockholm Gerontology Research Center, Stockholm, Sweden. · Am J Geriatr Psychiatry. · Pubmed #18591580 No free full text.

Abstract: OBJECTIVES: Our aims were to 1) detect the occurrence of three mild cognitive impairment (MCI) subtypes in the general population; 2) identify cases of cognitive impairment which are not detected by current operational criteria for MCI and; 3) determine the predictive value of the subtypes for identifying future Alzheimer disease (AD). DESIGN: Three-year prospective study. SETTING: Population-based Swedish study, the Kungsholmen Project. PARTICIPANTS: Three hundred seventy-nine nondemented older adults aged 75-95. MEASUREMENTS: Standard plus modified MCI criteria were applied at baseline. In the modified definitions, the requirement for normal general cognition was removed. A category for persons without MCI who had only global cognitive deficits was added. Three-year progression to AD was assessed (DSM-III-R criteria). RESULTS: Occurrence per 100 nondemented persons of MCI-amnestic, MCI-multidomains, and MCI-single-nonmemory was 2.1%, 1.8%, and 7.2%, respectively. When applying modified definitions for MCI-amnestic and MCI-multidomains, the occurrence almost doubled. Seven percent of the sample had impairment on a global cognitive task but performed at normal levels on all other domain-specific tasks. MCI-multidomains showed the highest progression to AD (hazard ratio [HR]: 23.6, 9.3-60.1). MCI-amnestic reached similar predictivity only when using the modified definition (HR: 17.9, 6.8-46.9). Even participants without MCI who had only global deficits had a ninefold risk of AD (HR: 9.1, 2.8-29.4). CONCLUSIONS: Two-thirds of MCI-multidomains, but only half of MCI-amnestic progress to AD. The standard MCI criteria failed to identify those people with global cognitive deficits who have, however, a high risk of progressing to AD.

Palmer K, Bäckman L, Winblad B, Fratiglioni L. · Aging Research Center, Karolinska Institutet, Stockholm, Sweden. · Int Psychogeriatr. · Pubmed #18257960 No free full text.

Abstract: OBJECTIVE:Clinical syndromes such as amnestic mild cognitive impairment (MCI) are highly predictive of future development of Alzheimer's disease (AD), but it is not known how many of the individuals that develop the disease can be identified with these syndromes. This study aims to determine how many individuals with AD show detectable symptoms or clinical signs of cognitive deficits three years before diagnosis.METHODS: 152 incident AD cases were identified in a dementia-free cohort of 1417 persons aged 75-95, after three-year follow-up from a prospective population-based study, the Kungsholmen Project. Symptoms of cognitive impairment including the subjective report of memory problems, and cognitive deficits were objectively measured with an extensive neuropsychological test battery at baseline. Incident AD was clinically diagnosed according to DSM-IIIR criteria at three-year follow-up.RESULTS: Only half of future AD cases reported subjective memory problems three years before diagnosis. More than one-third of incident AD cases did not exhibit detectable deficits in any of the investigated specific cognitive domains. Only 38.3% had both subjective complaints and domain-specific cognitive deficits.CONCLUSIONS: Symptoms and signs currently used to define MCI are not always present in persons who develop AD. Increasing the number of potentially identifiable and treatable preclinical AD cases is unfeasible unless more sensitive subjective and objective markers are identified. Furthermore, as only half of future AD cases report subjective memory problems three years before diagnosis, the number of persons coming to the attention of medical care is limited.

Eriksson UK, Gatz M, Dickman PW, Fratiglioni L, Pedersen NL. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #18097143 No free full text.

Abstract: BACKGROUND: Inflammation is associated with Alzheimer's disease (AD) and dementia. In light of the chronic inflammatory properties of the atopic disorders asthma, eczema and rhinitis, we hypothesized an association with dementia. METHODS: Self-reported asthma, eczema or rhinitis was assessed (prior to dementia follow-up) through questionnaires in the 1960s or 1970s in twins from the population-based Swedish Twin Registry. Dementia was assessed both longitudinally (n = 22,188), through linkages to two population-based registers, and cross-sectionally (n = 7,800), through telephone cognitive screening followed by a clinical evaluation of suspects of dementia. Risk ratios were estimated with Cox and logistic regression models controlling for vascular disease and genetic confounding. RESULTS: In the longitudinal study, a history of atopy was positively associated with dementia (HR = 1.16; 1.01-1.33). In the cross-sectional study we found overall lower risks, none of which was statistically significant. Asthma was associated with a shorter survival time following AD onset. CONCLUSIONS: Atopy is associated with a modestly increased risk of AD and dementia that is not mediated by vascular disease or due to genetic confounding. A history of asthma is associated with shorter life expectancy after AD diagnosis.

Palmer K, Berger AK, Monastero R, Winblad B, Bäckman L, Fratiglioni L. · Aging Research Center, Karolinska Institutet, Stockholm, Sweden. · Neurology. · Pubmed #17485646 No free full text.

Abstract: OBJECTIVE: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI). METHOD: We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria. RESULTS: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom). CONCLUSIONS: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.

Monastero R, Palmer K, Qiu C, Winblad B, Fratiglioni L. · Aging Research Center, Division of Geriatric Epidemiology, Department for Neurobiology, Health Care Sciences, and Society, Karolinska Institutet, Stockholm Gerontology Research Center, Stockholm, Sweden. · Am J Geriatr Psychiatry. · Pubmed #17194816 No free full text.

Abstract: OBJECTIVES: The objectives of this study were to investigate the relation of vascular, neuropsychiatric, social, and frailty-related factors with "Cognitive impairment, no dementia" (CIND) and to verify their effect independently of future progression to Alzheimer disease (AD). METHODS: Seven hundred eighteen subjects aged 75+ years who attended baseline, 3- and 6-year follow-up examinations of the Kungsholmen Project, a Swedish prospective cohort study, were studied. CIND was defined according to the performance on the Mini-Mental State Examination. Potential risk factors were collected at baseline and clustered according to four research hypotheses (frailty, vascular, neuropsychiatric, and social hypothesis), each representing a possible pathophysiological mechanism of CIND independently of subsequent development of AD. RESULTS: Over a mean 3.4 years of follow up, 82 participants (11.4%) developed CIND. When the population was subsequently followed for a mean of 2.7 years, subjects with CIND had a threefold increased risk to progress to AD. After multiple adjustments, including adjustment for the development of AD at the 6-year follow up, risk factors for CIND were hip fracture, polypharmacy, and psychoses. CONCLUSIONS: The results suggest that not only the AD-type neurodegenerative process, but also neuropsychiatric- and frailty-related factors may induce cognitive impairment in nondemented elderly. These findings may have relevant preventive and therapeutic implications.

Xu W, Qiu C, Winblad B, Fratiglioni L. · Aging Research Center, Karolinska Institutet, Stockholm, Sweden. · Diabetes. · Pubmed #17192484 links to  free full text

Abstract: To verify the hypothesis that borderline diabetes may increase the risk of dementia and Alzheimer's disease, a community-based cohort of 1,173 dementia- and diabetes-free individuals aged >or=75 years was longitudinally examined three times to detect patients with dementia and Alzheimer's disease (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria). Borderline diabetes was defined as a random plasma glucose level of 7.8-11.0 mmol/l. Data were analyzed using Cox proportional hazards models. During the 9-year follow-up, 397 subjects developed dementia, including 307 Alzheimer's cases. At baseline, 47 subjects were identified with borderline diabetes. Borderline diabetes was associated with adjusted hazard ratios (95% CIs) of 1.67 (1.04-2.67) for dementia and 1.77 (1.06-2.97) for Alzheimer's disease; the significant associations were present after additional adjustment for future development of diabetes. Stratified analysis suggested a significant association between borderline diabetes and Alzheimer's disease only among noncarriers of APOE epsilon4 allele. There was an interaction between borderline diabetes and severe systolic hypertension on the risk of Alzheimer's disease (P = 0.04). We conclude that borderline diabetes is associated with increased risks of dementia and Alzheimer's disease; the risk effect is independent of the future development of diabetes. Borderline diabetes may interact with severe systolic hypertension to multiply the risk of Alzheimer's disease.

Björk BF, Katzov H, Kehoe P, Fratiglioni L, Winblad B, Prince JA, Graff C. · Karolinska Institutet, Department NVS, Division of KI-Alzheimer Disease Research Center, SE-141 57 Huddinge, Sweden. · Neurobiol Aging. · Pubmed #16876916 No free full text.

Abstract: Insulin degrading enzyme (IDE) is one of the principal proteases involved in the degradation of the beta-amyloid peptide, which is the major constituent of senile plaques in Alzheimer's disease (AD) brains. Previous association studies between AD and IDE have produced inconsistent results which may be indicative of a need for larger case-control series to identify what may be a relatively small effect size. Thus, we performed a large association study using four SNPs in the 276-kb haplotype block in and around IDE (IDE_7, IDE_9, IDE_14 and HHEX_23) in a previously unpublished Swedish and a UK case-control series, and combined our data with a previously reported Swedish case-control sample set from Prince et al., 2003. The combined genotype data from 1269 late-onset AD cases and 980 controls yielded a significant association to IDE_9 located in the 3'-end of the IDE gene after conservative multiple testing Bonferroni correction (p=0.005). The effect seemed to predominate in male cases. However, we did not observe a globally significant association to haplotypes generated from three "tag" SNPs. These findings indicate a role for IDE in AD, and provide models that may improve chances of further independent replication.

Qiu C, Winblad B, Marengoni A, Klarin I, Fastbom J, Fratiglioni L. · Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Olivecronas väg 4, S-113 82 Stockholm, Sweden. · Arch Intern Med. · Pubmed #16682574 links to  free full text

Abstract: BACKGROUND: Heart failure has been linked to cognitive impairment in several previous studies, but to our knowledge, no investigations have explored the relationship between heart failure and the risk of dementia. We sought to examine the hypothesis that heart failure is a risk factor for dementia and Alzheimer disease. METHODS: A community-based cohort of 1301 individuals 75 years or older and without dementia in Stockholm, Sweden, was examined 3 times over a 9-year period to detect patients with dementia and Alzheimer disease using the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Heart failure was defined according to the guidelines of the Task Force on Heart Failure of the European Society of Cardiology by integrating clinical symptoms and signs with inpatient register entries and use of cardiac medications. Data were analyzed using Cox proportional hazards models with adjustment for major potential confounders. RESULTS: During the 6534 person-years of follow-up (mean, 5.02 years per person), 440 subjects were diagnosed as having dementia, including 333 with Alzheimer disease. At baseline, heart failure was identified in 205 subjects. Heart failure was associated with a multi-adjusted hazard ratio (HR) of 1.84 (95% confidence interval [CI], 1.35-2.51) for dementia and 1.80 (95% CI, 1.25-2.61) for Alzheimer disease. Use of antihypertensive drugs (83% of which are diuretics) seemed to reduce dementia risk due to heart failure (HR, 1.38; 95% CI, 0.99-1.94). Heart failure and low diastolic pressure (< 70 mm Hg) had an additive effect on the risk for dementia (HR, 3.07; 95% CI, 1.67-5.61). CONCLUSIONS: Heart failure is associated with an increased risk of dementia and Alzheimer disease in older adults. Antihypertensive drug therapy may partially counteract the risk effect of heart failure on dementia disorders.

Qiu CX, Winblad B, Fratiglioni L. · Aging Research Center, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm, Sweden. · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #16676611 No free full text.

Abstract: OBJECTIVE: It is known that dementia is a multi-factorial disorder, but the etiological factors other than aging remain to be explored, hence we sought to investigate the risk factors of dementia and Alzheimer's disease (AD). METHODS: We followed a community-based dementia-free cohort (n = 1301) aged 75 years and over in Stockholm, Sweden. Baseline data were obtained through a structured interview and extensive clinical examination, or by reviewing the inpatient register database. We used the DSM-III-R criteria to define dementia and AD cases. RESULTS: Over six years of a follow-up program,350 subjects were diagnosed as dementia, including 260 Alzheimer cases. Multiple Cox regression analysis suggested that older age,low education (< 8 years), cognitive impairment, functional disability (ADL > or = 1), low diastolic pressure (< 70 mm Hg), diabetes mellitus, coronary heart disease, and APOEepsilon4 allele were significantly or marginally associated with subsequent development of dementia and AD. Dementia was related also to stroke and atrial fibrillation. Antihypertensive drug use was associated with a lower risk of AD and dementia. CONCLUSIONS: Our study revealed that some sociodemographic features, cognitive and physical dysfunctions, vascular disorders, and genetic susceptibility were major risk factors for dementia and AD. Use of antihypertensive drugs might protect against the dementing disorders in a very old population.

Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA. · Arch Gen Psychiatry. · Pubmed #16461860 links to  free full text

Abstract: CONTEXT: Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME MEASURES: All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. CONCLUSIONS: In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, Anonymous00221. · Section of Epidemiology, Institute of Psychiatry, King's College, London, UK. · Lancet. · Pubmed #16360788 No free full text.

Abstract: BACKGROUND: 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. METHODS: 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. FINDINGS: Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81.1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. INTERPRETATION: We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.

McArdle JJ, Small BJ, Bäckman L, Fratiglioni L. · Department of Psychology, University of Southern California, Los Angeles 90089, USA. · J Geriatr Psychiatry Neurol. · Pubmed #16306246 No free full text.

Abstract: This article explores new statistical methodologies for using longitudinal data in the early prediction of Alzheimer's disease (AD). Specifically, the authors examine some new techniques that allow the joint or "shared" estimation of longitudinal components based on both duration (survival) and quantitative changes (growth curves). These new shared growth-survival parameter models may be used to characterize the declining functions that anticipate the onset of AD. The authors apply these models to data from the Kungsholmen Project, a longitudinal study of aging in Stockholm, Sweden. They examine age-based survival-frailty models for the onset of AD, latent growth-decline curve models for changes in cognition over age, and 3 alternative forms of models for the shared relationships of survival and early cognitive decline. The accuracy and reliability of this approach is considered for a better understanding of the developmental course of AD in these data, including the potential removal of biases due to subject selection.

Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kåreholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A. · Aging Research Center, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm, Sweden. · Arch Neurol. · Pubmed #16216938 links to  free full text

Abstract: BACKGROUND: Vascular risk factors play a role in the development of dementia, including Alzheimer disease (AD). However, little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia. OBJECTIVE: To investigate the relation between midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD. DESIGN AND SETTING: 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 reexamination in 1998. MAIN OUTCOME MEASURES: Dementia and AD. RESULTS: Obesity at midlife (body mass index>30 kg/m2) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables (odds ratio [OR], 2.4 [95% confidence interval (CI), 1.2-5.1]). The association was somewhat modified by further adjusting for midlife blood pressure, total cholesterol level, and smoking (OR, 2.1 [95% CI, 1.0-4.6]) and also for apolipoprotein E genotype and history of vascular disorders (OR, 1.9 [95% CI, 0.8-4.6]). Midlife obesity, high total cholesterol level, and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor, and they increased the risk additively (OR, 6.2 for the combination). CONCLUSIONS: Obesity at midlife is associated with an increased risk of dementia and AD later in life. Clustering of vascular risk factors increases the risk in an additive manner. The role of weight reduction for the prevention of dementia needs to be further investigated.