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Find video protocols related to scientific articles indexed in Pubmed.
Temporal Trends of Functional Dependence and Survival Among Older Adults From 1991 to 2010 in Sweden: Toward a Healthier Aging.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 11-15-2014
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Declines in functional dependence among older adults were observed before the 1990s, but there is uncertainty about subsequent trends. Our study aimed to verify the temporal trends in disability during 1991-2010 in an older Swedish population and to estimate the associated changes in survival.
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Changes in perceptual speed and white matter microstructure in the corticospinal tract are associated in very old age.
Neuroimage
PUBLISHED: 08-17-2014
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The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103years) assessed twice with a retest interval of 2.3years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition.
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Cognitive functioning among patients with diabetic foot.
J. Diabetes Complicat.
PUBLISHED: 07-15-2014
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Using diabetic foot (DF) as an indicator of severe diabetes, we aimed to investigate the cognitive profile of DF patients and the relations between cognitive functioning and both diabetes complications and comorbidities.
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Magnified effects of the COMT gene on white-matter microstructure in very old age.
Brain Struct Funct
PUBLISHED: 03-28-2014
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Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.
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Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts.
Epidemiology
PUBLISHED: 03-05-2014
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Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death.
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Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression.
Neuropsychologia
PUBLISHED: 01-16-2014
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The KIBRA (rs17070145) C-allele and the CLSTN2 (rs6439886) T-allele have both been associated with poorer episodic memory performance. Given that episodic memory is affected in depression, we hypothesized that the combination of these risk alleles would be particularly detrimental to episodic memory performance in depressed persons. In the population-based SNAC-K study, 2170 participants (? 60 years) without dementia (DSM-IV criteria) and antidepressant pharmacotherapy were clinically examined and diagnosed following ICD-10 criteria for unipolar depression, and genotyped for KIBRA and CLSTN2. Participants were categorized according to unipolar depression status (yes, no) and genotype combinations (KIBRA: CC, any T; CLSTN2: TT, any C). Critically, a three-way interaction effect showed that the CC/TT genotype combination was associated with poorer episodic recall and recognition performance only in depressed elderly persons, with depressed CC/TT carriers consistently performing at the lowest level. This finding supports the view that effects of genetic polymorphisms on cognitive functioning may be most easily disclosed at suboptimal levels of cognitive ability, such as in old-age depression.
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Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: results from the ESCAPE and TRANSPHORM projects.
Environ Int
PUBLISHED: 01-16-2014
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Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only.
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Neuropathologic assessment of dementia markers in identical and fraternal twins.
Brain Pathol.
PUBLISHED: 01-15-2014
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Twin studies are an incomparable source of investigation to shed light on genetic and non-genetic components of neurodegenerative diseases, as Alzheimer's disease (AD). Detailed clinicopathologic correlations using twin longitudinal data and post-mortem examinations are mostly missing. We describe clinical and pathologic findings of seven monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in MZ than DZ twins. Greater neuropathologic concordance was found for ?-amyloid than tau pathology within the pairs. ApoE4 was associated with higher ?-amyloid and earlier dementia onset, and importantly, higher frequency of other co-occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with AD pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in AD, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non-genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in AD.
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Incidence and predictors of multimorbidity in the elderly: a population-based longitudinal study.
PLoS ONE
PUBLISHED: 01-01-2014
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We aimed to calculate 3-year incidence of multimorbidity, defined as the development of two or more chronic diseases in a population of older people free from multimorbidity at baseline. Secondly, we aimed to identify predictors of incident multimorbidity amongst life-style related indicators, medical conditions and biomarkers.
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Valentina Escott-Price, Celine Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L Destefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, , Andrew D Johnson, Agustin Ruíz, Marie-Therese Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimón, Alberto Lleó, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renée F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-Francois Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramírez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams.
PLoS ONE
PUBLISHED: 01-01-2014
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Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
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A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI.
PLoS ONE
PUBLISHED: 01-01-2014
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The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts.
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Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project.
Lancet
PUBLISHED: 12-09-2013
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Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants.
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Cognitive decline, dietary factors and gut-brain interactions.
Mech. Ageing Dev.
PUBLISHED: 07-03-2013
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Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.
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Sociodemographic determinants of diet quality of the EU elderly: a comparative analysis in four countries.
Public Health Nutr
PUBLISHED: 05-09-2013
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OBJECTIVE: To investigate the sociodemographic determinants of diet quality of the elderly in four EU countries. DESIGN: Cross-sectional study. For each country, a regression was performed of a multidimensional index of dietary quality v. sociodemographic variables. SETTING: In Finland, Finnish Household Budget Survey (1998 and 2006); in Sweden, SNAC-K (2001-2004); in the UK, Expenditure & Food Survey (2006-07); in Italy, Multi-purpose Survey of Daily Life (2009). SUBJECTS: One- and two-person households of over-50s (Finland, n 2994; UK, n 4749); over-50 s living alone or in two-person households (Italy, n 7564); over-60 s (Sweden, n 2023). RESULTS: Diet quality among the EU elderly is both low on average and heterogeneous across individuals. The regression models explained a small but significant part of the observed heterogeneity in diet quality. Resource availability was associated with diet quality either negatively (Finland and UK) or in a non-linear or non-statistically significant manner (Italy and Sweden), as was the preference for food parameter. Education, not living alone and female gender were characteristics positively associated with diet quality with consistency across the four countries, unlike socio-professional status, age and seasonality. Regional differences within countries persisted even after controlling for the other sociodemographic variables. CONCLUSIONS: Poor dietary choices among the EU elderly were not caused by insufficient resources and informational measures could be successful in promoting healthy eating for healthy ageing. On the other hand, food habits appeared largely set in the latter part of life, with age and retirement having little influence on the healthiness of dietary choices.
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Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults.
Exp. Gerontol.
PUBLISHED: 04-25-2013
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Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but ?-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimers disease.
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A Change in Sleep Pattern May Predict Alzheimer Disease.
Am J Geriatr Psychiatry
PUBLISHED: 04-21-2013
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Sleep problems may adversely affect neuronal health. We examined a subjective report of change (reduced duration and/or depth) in sleep pattern in relation to subsequent risk of incident all-cause dementia and Alzheimer disease (AD) over 9 years.
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Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden.
Neurology
PUBLISHED: 04-17-2013
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To explore whether prevalence, survival, and incidence of dementia have changed from 1987-1994 to 2001-2008 in Stockholm, Sweden.
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Genetic effects on old-age cognitive functioning: a population-based study.
Psychol Aging
PUBLISHED: 01-02-2013
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Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ?4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.
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The Influence of Multimorbidity on Clinical Progression of Dementia in a Population-Based Cohort.
PLoS ONE
PUBLISHED: 01-01-2013
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Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia.
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Associations between White Matter Microstructure and Cognitive Performance in Old and Very Old Age.
PLoS ONE
PUBLISHED: 01-01-2013
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Increasing age is associated with deficits in a wide range of cognitive domains as well as with structural brain changes. Recent studies using diffusion tensor imaging (DTI) have shown that microstructural integrity of white matter is associated with cognitive performance in elderly persons, especially on tests that rely on perceptual speed. We used structural equation modeling to investigate associations between white matter microstructure and cognitive functions in a population-based sample of elderly persons (age ? 60 years), free of dementia, stroke, and neurological disorders (n = 253). Participants underwent a magnetic resonance imaging scan, from which mean fractional anisotropy (FA) and mean diffusivity (MD) of seven white matter tracts were quantified. Cognitive functioning was analyzed according to performance in five task domains (perceptual speed, episodic memory, semantic memory, letter fluency, and category fluency). After controlling for age, FA and MD were exclusively related to perceptual speed. When further stratifying the sample into two age groups, the associations were reliable in the old-old (?78 years) only. This relationship between white matter microstructure and perceptual speed remained significant after excluding persons in a preclinical dementia phase. The observed pattern of results suggests that microstructural white matter integrity may be especially important to perceptual speed among very old adults.
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Is midlife occupational physical activity related to disability in old age? The SNAC-Kungsholmen study.
PLoS ONE
PUBLISHED: 01-01-2013
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Leisure-time physical activity (PA) has been established to be related to more years lived without disability. However, less is known about the relationship between occupational PA and disability in old age. The aim of the study was 1) to investigate whether midlife occupational PA is related to late-life disability, and 2) to test the hypothesis that the association differs according to the occupational categories of blue and white collar work.
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Association of cardiovascular burden with mobility limitation among elderly people: a population-based study.
PLoS ONE
PUBLISHED: 01-01-2013
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Cardiovascular risk factors (CRFs) such as smoking and diabetes have been associated with mobility limitations among older adults. We seek to examine to what extent individual and aggregated CRFs and cardiovascular diseases (CVDs) are associated with mobility limitation.
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The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age.
Front Hum Neurosci
PUBLISHED: 01-01-2013
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Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimers disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 60-87 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 × 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r (2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE ?4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R (2) = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R (2) = 0.08) "risk" alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE ?4 carriers with additional TOMM40 "risk" alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
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Work-related stress may increase the risk of vascular dementia.
J Am Geriatr Soc
PUBLISHED: 12-16-2011
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To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimers disease (AD), and vascular dementia (VaD).
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Cost of disorders of the brain in Europe 2010.
Eur Neuropsychopharmacol
PUBLISHED: 09-15-2011
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The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.
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Education halves the risk of dementia due to apolipoprotein ?4 allele: a collaborative study from the Swedish brain power initiative.
Neurobiol. Aging
PUBLISHED: 08-14-2011
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A number of studies have explored the relationships of apolipoprotein E (APOE) genotype and education with dementia over the last decade. However, observations concerning the possible modifying effect of education on the APOE-dementia association are limited. The objective of this study was to test the hypothesis that education may decrease the risk of APOE ?4 on dementia. Pooled data from 3 major population-based studies in Northern Europe were used in this study, with a total of 3436 participants aged 65 and older derived from the Kungsholmen project and the Gothenburg Birth Cohort studies in Sweden, and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project in Finland. The main outcome measure was dementia, which was diagnosed in 219 persons according to standard criteria. APOE ?4 was associated with increased risk of dementia independent of the effect of education (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.4 for 1 ?4 carrier and OR, 3.7; 95% CI, 1.8-7.2 for 2 ?4 carriers). High education (8 years and more) was related to a lower dementia risk (OR, 0.5; 95% CI, 0.3-0.6). An interaction between education and APOE ?4 was observed. Compared with those with less education and no ?4, the odds of dementia among persons with low education who carried any ?4 allele was 2.7 (95% CI, 1.9-3.9), and 1.2 (0.7-1.8) if they had higher education. This study suggests that genetic (APOE ?4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE ?4 on dementia occurrence.
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Association of blood pressure and hypertension with the risk of Parkinson disease: the National FINRISK Study.
Hypertension
PUBLISHED: 05-02-2011
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Cardiovascular risk factors, such as diabetes mellitus and central obesity, have been associated with Parkinson disease (PD), but data on blood pressure and PD are lacking. We sought to examine the association of blood pressure and hypertension with the risk of PD among men and women. This study consisted of 7 surveys (1972-2002) on representative samples of the general population in Finland (National FINRISK Study). A total number of 59 540 participants (age 25 to 74 years; 51.8% women) who were free of PD and stroke at baseline were prospectively followed until December 31, 2006, to identify incident PD cases using the National Social Insurance Register database. Cox proportional hazards models were constructed to estimate the hazard ratio of PD associated with blood pressure. During a mean follow-up period of 18.8 years (SD: 10.2 years), 423 men and 371 women were ascertained to have developed PD. In women, compared with normotensive subjects (<130/80 mm Hg), the multivariable-adjusted hazard ratios of PD associated with high-normal blood pressure (130 to 139/80 to 89 mm Hg) and hypertension (?140/90 mm Hg or use of antihypertensive agents) were 1.63 (95% CI: 1.07 to 2.47) and 1.62 (95% CI: 1.09 to 2.42). There was no significant association between blood pressure and PD risk in men. The multivariable-adjusted hazard ratios of PD associated with use of antihypertensive agents were 1.08 (95% CI: 0.79 to 1.48) in men and 1.03 (95% CI: 0.76 to 1.38) in women. This study suggests that, in women, above-optimal blood pressure, including high-normal blood pressure and hypertension, is associated with an increased risk of PD. Optimal control of blood pressure in women may reduce the incidence of PD.
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The world of dementia beyond 2020.
J Am Geriatr Soc
PUBLISHED: 04-13-2011
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Counterpoised against dire projections of the tripling of the prevalence of dementia over the next 40 years are major developments in diagnostic biomarkers, neuroimaging, the molecular biology of Alzheimers disease (AD), epidemiology of risk and protective factors, and drug treatments-mainly targeting the amyloid pathway, tau protein, and immunotherapy-that may have the potential to modify the progression of AD. Drug combinations and presymptomatic treatments are also being investigated. Previous trials of dementia-modifying drugs have not shown benefit, and even if current Phase III trials prove successful, these drugs will not eradicate other dementias, could (if not curative) increase dementia duration and prevalence, and are unlikely to come onto the market before 2020. In the meantime, delaying the onset of dementia by even 2 years would have significant economic and societal effects. This article provides an overview of current achievements and potentials of basic and clinical research that might affect the development of dementia prevalence and care within the near future.
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Pain treatment in elderly persons with and without dementia: a population-based study of institutionalized and home-dwelling elderly.
Drugs Aging
PUBLISHED: 03-25-2011
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Several previous studies have reported an undertreatment of pain in elderly persons with dementia. It has also been suggested that persons with dementia may be at risk for inappropriate treatment of pain with psychotropics.
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Trajectories of cognitive decline following dementia onset: what accounts for variation in progression?
Dement Geriatr Cogn Disord
PUBLISHED: 02-11-2011
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Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified.
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Aging with multimorbidity: a systematic review of the literature.
Ageing Res. Rev.
PUBLISHED: 01-30-2011
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A literature search was carried out to summarize the existing scientific evidence concerning occurrence, causes, and consequences of multimorbidity (the coexistence of multiple chronic diseases) in the elderly as well as models and quality of care of persons with multimorbidity. According to pre-established inclusion criteria, and using different search strategies, 41 articles were included (four of these were methodological papers only). Prevalence of multimorbidity in older persons ranges from 55 to 98%. In cross-sectional studies, older age, female gender, and low socioeconomic status are factors associated with multimorbidity, confirmed by longitudinal studies as well. Major consequences of multimorbidity are disability and functional decline, poor quality of life, and high health care costs. Controversial results were found on multimorbidity and mortality risk. Methodological issues in evaluating multimorbidity are discussed as well as future research needs, especially concerning etiological factors, combinations and clustering of chronic diseases, and care models for persons affected by multiple disorders. New insights in this field can lead to the identification of preventive strategies and better treatment of multimorbid patients.
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Brain aging: lessons from community studies.
Nutr. Rev.
PUBLISHED: 11-25-2010
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Dementia is an acquired highly disabling syndrome common among elderly people. Alzheimers disease is the most frequent type of dementia, and its prevalence is rapidly increasing due to the aging of populations. Therefore, the need to find effective preventive means is pressing. Population studies allow identification of risk/protective factors for dementia/Alzheimers disease, thus leading to preventive strategies that can be implemented in the general population to reduce the incidence of this disorder. Presented here is an overview of the main findings of epidemiological studies on nutritional factors and nutrition-related pathological conditions, as related to dementia and Alzheimers disease.
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Onset and rate of cognitive change before dementia diagnosis: findings from two Swedish population-based longitudinal studies.
J Int Neuropsychol Soc
PUBLISHED: 11-17-2010
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We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.
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Accelerated progression from mild cognitive impairment to dementia in people with diabetes.
Diabetes
PUBLISHED: 08-16-2010
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The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia.
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Work-related exposure to extremely low-frequency magnetic fields and dementia: results from the population-based study of dementia in Swedish twins.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 07-09-2010
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We examined the association between extremely low-frequency magnetic fields (EMF) and the risk of dementia and Alzheimers disease using all 9,508 individuals from the Study of Dementia in Swedish Twins (HARMONY) with valid occupational and diagnostic data.
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A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations.
Brain Res.
PUBLISHED: 04-26-2010
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Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).
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Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study.
Int Psychogeriatr
PUBLISHED: 12-04-2009
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Brain atrophy in Alzheimers disease (AD) includes not only AD-specific brain atrophy but also the atrophy induced by normal aging. Atrophy of the hippocampus has been one diagnostic marker of AD, but it was also found to emerge in healthy adults, along with increasing age. It was reported that the important age when age-related shrinkage of the hippocampus starts was around the mid-40s. The aim is to study the aging atrophy speed and acceleration of brain atrophy in a cross-sectional database, to identify the age at which acceleration of hippocampal atrophy starts in non-demented elderly persons.
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APOE-related mortality: effect of dementia, cardiovascular disease and gender.
Neurobiol. Aging
PUBLISHED: 10-31-2009
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Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimers disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.
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Genetic and biochemical studies of SNPs of the mitochondrial A beta-degrading protease, hPreP.
Neurosci. Lett.
PUBLISHED: 10-07-2009
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Several studies suggest mitochondrial dysfunction as a possible mechanism underlying the development of Alzheimer disease (AD). There is data showing that amyloid-beta (A beta) peptide is present in AD brain mitochondria. The human presequence protease (hPreP) was recently shown to be the major mitochondrial A beta-degrading enzyme. We investigated if there is an increased susceptibility to AD, which can be attributed to genetic variation in the hPreP gene PITRM1 and if the proteolytic efficiency of recombinant hPreP variants is affected. When a total of 673 AD cases and 649 controls were genotyped for 18 single nucleotide polymorphisms (SNPs), no genetic association between any of the SNPs and the risk for AD was found. In contrast, functional analysis of four non-synonymous SNPs in hPreP revealed a decreased activity compared to wild type hPreP. Using A beta, the presequence of ATP synthase F(1)beta subunit and a fluorescent peptide as substrates, the lowest activity was observed for the hPreP(A525D) variant, corresponding to rs1224893, which displayed only 20-30% of wild type activity. Furthermore, the activity of all variants was restored by the addition of Mg(2+), suggesting an important role for this metal during proteolysis. In conclusion, our data suggest that genetic variation in the hPreP gene PITRM1 may potentially contribute to mitochondrial dysfunctions.
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Prevention of common neurodegenerative disorders in the elderly.
Exp. Gerontol.
PUBLISHED: 08-06-2009
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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. Alzheimers 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 Parkinsons disease.
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Low diastolic pressure and risk of dementia in very old people: a longitudinal study.
Dement Geriatr Cogn Disord
PUBLISHED: 07-29-2009
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Midlife high blood pressure is linked to late-life dementia. We sought to investigate the temporal relation of blood pressure to the risk of dementia and Alzhei-mers disease (AD) among older adults.
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Leisure activities in late life in relation to dementia risk: principal component analysis.
Dement Geriatr Cogn Disord
PUBLISHED: 06-27-2009
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To explore the underlying dimensions of a set of interrelated lifestyle factors and test the hypothesis that an active lifestyle may protect against dementia.
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Depression as a risk factor or prodromal feature for dementia? Findings in a population-based sample of Swedish twins.
Psychol Aging
PUBLISHED: 06-03-2009
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This study tested whether history of depression is associated with an increased likelihood of dementia, and whether a first depressive episode earlier in life is associated with increased dementia risk, or whether only depressive episodes close in time to dementia onset are related to dementia. Depression information came from national hospital discharge registries, medical history, and medical records. Dementia was diagnosed clinically. In case-control results, individuals with recent registry-identified depression were 3.9 times more likely than those with no registry-identified depression history to have dementia, whereas registry-identified depression earlier in life was not associated with dementia risk. Each 1-year increase in time between depression onset and dementia onset or equivalent age decreased the likelihood of dementia by 8.4%. In co-twin control analyses, twins with prior depression were 3.0 times more likely to have dementia than their nondepressed twin partners, with a similar age of depression gradient. These findings suggest that after partially controlling for genetic influences, late-life depression for many individuals may be a prodrome rather than a risk factor for dementia.
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Mentally stimulating activities at work during midlife and dementia risk after age 75: follow-up study from the Kungsholmen Project.
Am J Geriatr Psychiatry
PUBLISHED: 05-21-2009
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Previous research has suggested that mental stimulation in different life periods may protect against dementia or delay disease onset. This study aimed to explore the association between work complexity factors at midlife and dementia risk in late life under the hypothesis that high work complexity may modulate the increased dementia risk due to low education.
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Atrial fibrillation, stroke and dementia in the very old: a population-based study.
Neurobiol. Aging
PUBLISHED: 04-11-2009
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We explored the association of chronic AF with stroke, dementia and Alzheimers disease (AD) among community-dwelling elderly people. The study population consisted of 685 individuals from Stockholm (The Kungsholmen Project) who were aged 78 years and were free of dementia and clinical stroke. During the 6-year follow-up, 170 subjects developed dementia, and 86 persons experienced first-ever stroke. The incidence rate (per 1000 person-years) of dementia, AD and first-ever stroke was 72.3, 52.2, and 52.2 in persons with AF and 63.8, 54.6 and 30.6 in those without AF, respectively. AF was associated with the hazard ratio of 1.8 (95%CI, 1.0-3.4) for first-ever stroke, but not significantly associated with dementia or AD.
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Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study.
Diabetes
PUBLISHED: 03-31-2009
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We aimed to verify the association between diabetes and the risk of dementia, Alzheimers disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association.
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Patterns of chronic multimorbidity in the elderly population.
J Am Geriatr Soc
PUBLISHED: 02-12-2009
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To describe patterns of comorbidity and multimorbidity in elderly people.
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Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinsons disease?
J Neural Transm
PUBLISHED: 01-13-2009
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The key symptoms of Parkinsons disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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Does vascular burden contribute to the progression of mild cognitive impairment to dementia?
Dement Geriatr Cogn Disord
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To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimers disease (AD).
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Adherence to physical exercise recommendations in people over 65--the SNAC-Kungsholmen study.
Eur J Public Health
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There is limited knowledge regarding to what extent the older population meet the recommendations of physical exercise, especially fitness-enhancing exercise. This study assessed participation in health- and fitness-enhancing exercises in people aged >65, and explored to what extent the possible differences in meeting current recommendations differs by age, gender and education.
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Can chronic multimorbidity explain the age-related differences in strength, speed and balance in older adults?
Aging Clin Exp Res
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It is known that physical performance declines with age in general, however there remains much to be understood in terms of age-related differences amongst older adults across a variety of physical components (such as speed, strength and balance), and particularly in terms of the role played by multimorbidity of chronic diseases. We aimed to detect the age-related differences across four components of physical performance and to explore to what extent chronic diseases and multimorbidity may explain such differences.
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Lifestyle, social factors, and survival after age 75: population based study.
BMJ
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To identify modifiable factors associated with longevity among adults aged 75 and older.
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Methodological challenges in designing dementia prevention trials - the European Dementia Prevention Initiative (EDPI).
J. Neurol. Sci.
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Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia. However, evidence from randomised controlled trials (RCT) showing effectiveness of interventions aimed at these risk factors in preventing or postponing dementia onset is still lacking. Three large RCTs on multi-component interventions to prevent dementia (preDIVA, FINGER, MAPT) have been initiated in Europe to address these issues. Irrespective of some methodological differences, all three studies target cardiovascular and lifestyle related risk factors. Collaboration within the newly founded European Dementia Prevention Initiative (EDPI) will allow for a comprehensive exploration of optimal target population, intervention and outcome measures, which are currently unknown. Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample-size calculations for future multi-national clinical trials on dementia prevention. Interventions aiming at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems, without generating high additional costs or burden on participants or physicians. As the optimal age for intervention precedes the optimal age for outcome assessment, traditional trial designs might lead to suboptimal timing of either of the two. Separation of intervention and outcome assessment in time is a potential solution, but requires studies with very long follow-up. International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies. Founding of EDPI is an important first step in this direction.
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Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population.
Acta Radiol
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It is important to have a replicable easy method for monitoring atrophy progression in Alzheimers disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy.
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How can elderly apolipoprotein E ?4 carriers remain free from dementia?
Neurobiol. Aging
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Apolipoprotein E (APOE) ?4 is a major risk factor for Alzheimers disease (AD) and dementia, but not all ?4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to ?4. A cognitively intact cohort (n = 932, age ? 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the ?4 was 1.39 (1.11-1.76), while the risk was reduced when ?4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among ?4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The ?4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE ?4. The ?4 carriers with these characteristics appear to have similar dementia-free survival time to non-?4 carriers.
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The dimensionality of between-person differences in white matter microstructure in old age.
Hum Brain Mapp
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Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60-87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general.
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Dementia after age 75: survival in different severity stages and years of life lost.
Curr Alzheimer Res
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Dementia is a known predictor of mortality, but little is known about disease duration. We therefore aimed to investigate the impact of dementia on survival by estimating years lived with the disease, in total and in different severity stages, and by comparing dementia to other major chronic disorders such as cancer and cardiovascular disease (CVD). During a 7.4-year follow-up of the Kungsholmen project, 371 incident dementia cases of the 1,307 dementia-free persons, aged 75+ at baseline, were clinically diagnosed (DSM-III-R criteria). Diagnoses of cancer and CVD were obtained from the national Stockholm Inpatient Registry System, active since 1969. Disease duration, hazard ratio (HR), and potential years of life lost (PYLL) were derived from Kaplan-Meier survival estimation, the Cox model, and standard life-table analysis, respectively. Dementia was a significant predictor of mortality (HR=1.7; 95% CI: 1.47-1.92) after adjustment for several covariates including comorbidity, accounting for 16% of all deaths. The mean (?SD) survival time after dementia diagnosis was 4.1 (?2.6) years, and more than 2 years were spent in moderate (14-month) and severe (12-month) stages. Women with dementia lived longer than men, as they survived longer in the severe stage (2.1 vs. 0.5 years among 75-84-year-old women compared to coetaneous men). The PYLL were 3.4 for dementia, 3.6 for CVD, and 4.4 for cancer. We found a similar impact of dementia and CVD on survival, but following diagnosis, persons with dementia, and especially women, spent half of their remaining lives in the severe disabling stages of the disease.
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Preclinical cognitive trajectories differ for Alzheimers disease and vascular dementia.
J Int Neuropsychol Soc
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We investigated differences between Alzheimers disease (AD) and vascular dementia (VaD) from the appearance of the first cognitive symptoms, focusing on both time of onset and rate of accelerated decline for different cognitive functions before dementia diagnosis. Data from a longitudinal population-based study were used, including 914 participants (mean age = 82.0 years, SD = 5.0) tested with a cognitive battery (word recall and recognition, Block Design, category fluency, clock reading) on up to four occasions spanning 10 years. We fit a series of linear mixed effects models with a change point to the cognitive data, contrasting each dementia group to a control group. Significant age-related decline was observed for all five cognitive tasks. Relative to time of diagnosis, the preclinical AD persons deviated from the normal aging curve earlier (up to 9 years) compared to the preclinical VaD persons (up to 6 years). However, once the preclinical VaD persons started to decline, they deteriorated at a faster rate than the preclinical AD persons. The results have important implications for identifying the two dementia disorders at an early stage and for selecting cognitive tasks to evaluate treatment effects for persons at risk of developing AD and VaD.
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