Browsing by Subject "Dementia"

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  • Strandberg, Timo; Tienari, Pentti (2019)
    Amyloiditeoriaa on jouduttu katsomaan uudesta näkökulmasta.
  • Rantalainen, Ville; Lahti, Jari; Kajantie, Eero; Tienari, Pentti; Eriksson, Johan G.; Raikkonen, Katri (2019)
    We tested if the epsilon 4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms. APOE epsilon 4 predicted higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI] 1.76, 7.70) across all statistical models, and when adjusted for rs405509 and rs440446. The number of minor alleles in rs405509 or rs440446 was not associated with dementia risk (hazard ratios
  • Korhonen, Kaarina; Tarkiainen, Lasse; Leinonen, Taina; Einiö, Elina; Martikainen, Pekka (2022)
    Background Depression is associated with an increased dementia risk, but the nature of the association in the long-term remains unresolved, and the role of sociodemographic factors mainly unexplored. Aims To assess whether a history of clinical depression is associated with dementia in later life, controlling for observed sociodemographic factors and unobserved factors shared by siblings, and to test whether gender, educational level and marital status modify the association. Method We conducted a national cohort study of 1 616 321 individuals aged 65 years or older between 2001 and 2018 using administrative healthcare data. A history of depression was ascertained from the national hospital register in the period 15-30 years prior to dementia follow-up. We used conventional and sibling fixed-effects Cox regression models to analyse the association between a history of depression, sociodemographic factors and dementia. Results A history of depression was related to an adjusted hazard ratio of 1.27 (95% CI 1.23-1.31) for dementia in the conventional Cox model and of 1.55 (95% CI 1.09-2.20) in the sibling fixed-effects model. Depression was related to an elevated dementia risk similarly across all levels of education (test for interaction, P = 0.84), but the association was weaker for the widowed than for the married (P = 0.003), and stronger for men than women (P = 0.006). The excess risk among men attenuated following covariate adjustment (P = 0.10). Discussion This study shows that a history of depression is consistently associated with later-life dementia risk. The results support the hypothesis that depression is an aetiological risk factor for dementia.
  • Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J.; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G.; Sääksjärvi, Katri; Shipley, Martin J.; Singh-Manoux, Archana; Gerszten, Robert E.; Wang, Thomas J.; Havulinna, Aki S.; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M. Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S.; Kivimäki, Mika; van Duijn, Cornelia M.; Seshadri, Sudha; Salomaa, Veikko (2018)
    Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
  • Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H. (2018)
    Background: Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline, in adults. Method: The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. Results: In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. Conclusions: The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. (C) 2018 Published by Elsevier Inc.
  • Nazu, Nazma Akter; Wikström, Katja; Lamidi, Marja-Leena; Lindström, Jaana; Tirkkonen, Hilkka; Rautiainen, Päivi; Laatikainen, Tiina (2020)
    Aims: To compare the quality of diabetes care among type 2 diabetes patients with and without mental disorders during six-year follow-up in North Karelia, Finland. Methods: All type 2 diabetes patients (n = 10190) were analysed using the electronic health records data from 2011-12 to 2015-16. The diabetes care was evaluated using the measurement activity and the achievement of the treatment targets for HbA1c and LDL. Results: Monitoring of HbA1c and LDL levels improved among all patient groups, except the dementia patients. The proportion of those achieving the HbA1c target declined and those achieving the LDL target improved in all patient groups. Differences in the changes of achievement of the target HbA1c level among patients with dementia and depression were observed when compared with those having only type 2 diabetes. Conclusions: This study highlights the challenge of glucose level management as the age and comorbidities of the patients related to the care and achievements of the treatment targets. Mental disorders that are likely to affect patients' adherence to medication and other treatments should be taken into account and more support for self-care should be provided to such patients. Improvement in the achievement of LDL target address the progress in the prevention of macrovascular complications. (C) 2020 The Authors. Published by Elsevier B.V.
  • Ylilauri, Maija P. T.; Hantunen, Sari; Lonnroos, Eija; Salonen, Jukka T.; Tuomainen, Tomi-Pekka; Virtanen, Jyrki K. (2022)
    Purpose To investigate if dairy, meat, and fish intakes associate with dementia and cognitive performance. Methods We included 2497 dementia-free men from Eastern Finland, aged 42-60 years in 1984-1989 at the baseline examinations. Data on cognitive tests [Mini Mental State Exam (MMSE), trail making test (TMT), verbal fluency test (VFL), selective reminding test (SRT), and Russell's adaptation of the visual reproduction test (VRT)] at the 4-year re-examinations were available for 482 men and on the ApoE phenotype for 1259 men. Data on dementia events were obtained by linkage to national health registers. Diet was assessed with baseline 4-day food records. Cox regression and analysis of covariance were used for analyses. Results During a mean 22-year follow-up, 337 men had a dementia diagnosis. Among the foods, only cheese intake associated with dementia risk (hazard ratio in the highest vs. the lowest quartile = 0.72, 95% confidence interval = 0.52-0.99, P-trend = 0.05). In the cognitive tests, higher non-fermented dairy and milk intakes associated with worse verbal fluency (VFT). Higher processed red meat intake associated with worse verbal (SRT) and visual memory (VRT), whereas higher unprocessed red meat intake associated with better general cognitive functioning (MMSE) and processing speed and executive functioning (TMT). Higher fish intake associated with better verbal memory (SRT). Among APOE-epsilon 4 carriers, especially non-fermented dairy intake associated with higher risk of dementia outcomes, and higher fish intake indicated better cognitive performance. Conclusion Although higher intake of some food groups associated with cognitive performance, we found little evidence for associations with dementia risk.
  • Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Antikainen, Riitta; Hulkkonen, Juha; Koikkalainen, Juha; Kemppainen, Nina; Lötjönen, Jyrki; Levälahti, Esko; Parkkola, Riitta; Pippola, Pauliina; Rinne, Juha; Strandberg, Timo; Tuomilehto, Jaakko; Vanninen, Ritva; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (BioMed Central, 2019)
    Abstract Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures. Methods FINGER targeted 1260 older individuals from the general Finnish population. Participants were 60–77 years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2 years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12). Results No significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer’s disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization group × time × cortical thickness interaction coefficient was 0.198 (p = 0.021). A similar trend was observed for higher hippocampal volume (group × time × hippocampus volume interaction coefficient 0.1149, p = 0.085). Conclusions The FINGER MRI exploratory sub-study did not show significant differences between the intervention and control groups on changes in regional brain volumes, regional cortical thicknesses, or WML volume after 2 years in at-risk elderly without substantial impairment. The cognitive benefits on processing speed of the FINGER intervention may be more pronounced in individuals with fewer structural brain changes on MRI at baseline. This suggests that preventive strategies may be more effective if started early, before the occurrence of more pronounced structural brain changes. Trial registration ClinicalTrials.gov, NCT01041989 . Registered January 5, 2010.
  • FINGER Study Grp; Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Antikainen, Riitta; Hulkkonen, Juha; Koikkalainen, Juha; Levälahti, Esko; Parkkola, Riitta; Pippola, Pauliina; Rinne, Juha; Strandberg, Timo; Tuomilehto, Jaakko; Vanninen, Ritva; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (2019)
    BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures.MethodsFINGER targeted 1260 older individuals from the general Finnish population. Participants were 60-77years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12).ResultsNo significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer's disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization groupxtimexcortical thickness interaction coefficient was 0.198 (p=0.021). A similar trend was observed for higher hippocampal volume (groupxtimexhippocampus volume interaction coefficient 0.1149, p=0.085).ConclusionsThe FINGER MRI exploratory sub-study did not show significant differences between the intervention and control groups on changes in regional brain volumes, regional cortical thicknesses, or WML volume after 2years in at-risk elderly without substantial impairment. The cognitive benefits on processing speed of the FINGER intervention may be more pronounced in individuals with fewer structural brain changes on MRI at baseline. This suggests that preventive strategies may be more effective if started early, before the occurrence of more pronounced structural brain changes.Trial registrationClinicalTrials.gov, NCT01041989. Registered January 5, 2010.
  • Kaivola, Karri; Kiviharju, Anna; Jansson, Lilja; Rantalainen, Ville; Eriksson, Johan G.; Strandberg, Timo E.; Laaksovirta, Hannu; Renton, Alan E; Traynor, Bryan J.; Myllykangas, Liisa; Tienari, Pentti (2019)
    The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.
  • FINGER Study Grp; Stephen, Ruth; Ngandu, Tiia; Liu, Yawu; Peltonen, Markku; Antikainen, Riitta; Kemppainen, Nina; Laatikainen, Tiina; Lötjönen, Jyrki; Rinne, Juha; Strandberg, Timo; Tuomilehto, Jaakko; Vanninen, Ritva; Soininen, Hilkka; Kivipelto, Miia; Solomon, Alina (2021)
    The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60-77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer's disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group x CAIDE change interaction beta coefficient = -0.40, p = .02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies.
  • van der Lee, Sven J.; Teunissen, Charlotte E.; Pool, Rene; Shipley, Martin J.; Teumer, Alexander; Chouraki, Vincent; van Lent, Debora Melo; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A.; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; van Dijk, Ko Willems; Weinhold, Leonie; Ikram, M. Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P. Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E.; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E. M.; Vasan, Ramachandran S.; Maier, Wolfgang; Peeters, Carel F. W.; Grabe, Hans Joergen; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayse; Boomsma, Dorret I.; van der Flier, Wiesje M.; Amin, Najaf; van Duijn, Cornelia M. (2018)
    Introduction: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. Methods: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. Results: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Discussion: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
  • Hale, Jo Mhairi; Schneider, Daniel C.; Mehta, Neil K.; Myrskylä, Mikko (2020)
    Prior studies have analyzed the burden of cognitive impairment, but often use potentially biased prevalence-based methods or measure only years lived with impairment, without estimating other relevant metrics. We use the Health and Retirement Study (1998–2014; n = 29,304) and the preferred incidence-based Markov-chain models to assess three key measures of the burden of cognitive impairment: lifetime risk, mean age at onset, and number of years lived impaired. We analyze both mild and severe cognitive impairment (dementia) and gender, racial/ethnic, and educational variation in impairment. Our results paint a multi-dimensional picture of cognitive health, presenting the first comprehensive analysis of the burden of cognitive impairment for the U.S. population age 50 and older. Approximately two out of three Americans experience some level of cognitive impairment at an average age of approximately 70 years. For dementia, lifetime risk for women (men) is 37% (24%) and mean age at onset 83 (79) years. Women can expect to live 4.2 years with mild impairment and 3.2 with dementia, men 3.5 and 1.8 years. A critical finding is that for the most advantaged groups (i.e., White and/or higher educated), cognitive impairment is both delayed and compressed toward the very end of life. In contrast, despite the shorter lives of disadvantaged subgroups (Black and/or lower educated), they experience a younger age of onset, higher lifetime risk, and more years cognitively impaired. For example, men with at least an Associate degree have 21% lifetime dementia risk, compared to 35% among men with less than high school education. White women have 6 years of cognitively-impaired life expectancy, compared to 12 and 13 years among Black women and Latinas. These educational and racial/ethnic gradients highlight the very uneven burden of cognitive impairment. Further research is required to identify the mechanisms driving these disparities in cognitive impairment.
  • Korpioja, Anita; Krüger, Johanna; Hurme-Niiranen, Anri; Solje, Eino; Katisko, Kasper; Lipponen, Joonas; Lehtilahti, Maria; Remes, Anne M.; Majamaa, Kari; Kytövuori, Laura (2022)
    Introduction: The biallelic repeat expansion (AAGGG)(exp) in RFC1 causes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recently, cognitive impairment has been reported in patients with CANVAS and a broader neurodegenerative process associated with RFC1 has been suggested. Furthermore, rare cases of multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis or CANVAS with features of dementia with Lewy bodies have been found. Objective: We hypothesized that the biallelic (AAGGG)(exp) is associated with neurodegeneration manifested as cognitive symptoms and that atypical RFC1 disease may be found among patients with cognitive disorder. Methods: Clinical data on nine patients with biallelic (AAGGG()exp) were reviewed and 564 patients with Alz-heimer's disease or frontotemporal dementia (FTD) were investigated for biallelic RFC1 (AAGGG)(exp). Results: Five patients with biallelic (AAGGG)(exp) were found with a cognitive impairment and in four of them the phenotype resembled FTD. However, biallelic (AAGGG)(exp) was not detected among patients with Alzheimer's disease or FTD. Conclusion: Cognitive impairment is a feature in patients with the biallelic (AAGGG)(exp), but the pathogenic expansion seems to be rare in patients with dementia. Studies on patients with diverse phenotypes would be useful to further explore the involvement of RFC1 in neuronal degeneration and to identify atypical phenotypes, which should be taken into account in clinical practice.
  • Sarkamo, Teppo (2018)
    Music has the capacity to engage auditory, cognitive, motor, and emotional functions across cortical and subcortical brain regions and is relatively preserved in aging and dementia. Thus, music is a promising tool in the rehabilitation of aging-related neurological illnesses, such as stroke and Alzheimer disease. As the population ages and the incidence and prevalence of these illnesses rapidly increases, music-based interventions that are enjoyable and effective in the everyday care of the patients are needed. In addition to formal music therapy, musical leisure activities, such as music listening and singing, which patients can do on their own or with a caregiver, are a promising way to support psychological well-being during aging and in neurological rehabilitation. This review article provides an overview of current evidence on the cognitive, emotional, and neural effects of musical leisure activities both during normal aging and in the rehabilitation and care of stroke patients and people with dementia. (C) 2017 Elsevier Masson SAS. All rights reserved.
  • Könönen, Maija (2020)
    This essay explores the various ways of talking about senility and how the two competing (or, possibly, complementing) discourses-the biomedical dementia discourse and the discourse of senility as part of "normal" aging-affect our perception of and attitudes toward old age. Moreover, I explore the role of fiction in articulating senility. As my approach combines critical gerontology with narratological analysis, it belongs to the burgeoning domain of literary gerontology, a discipline that embraces various literary genres from fiction to nonfiction. This double perspective of literary studies and cultural gerontology makes it possible to examine senility as a historically and culturally specific concept and phenomenon. My aim is to demonstrate with two examples from contemporary Russian short prose (Nina Katerli's story "Na dva golosa" [In Two Voices] and Nina Sadur's story "Stul" [The Chair]) how a literary work can be related to prevailing cultural, sociological, and medical discourses on and norms of aging. With tools of narratology I shed light on the literary devices deployed in the stories to articulate the experience of senility from the viewpoint of the elderly protagonists themselves.
  • Raggi, Martina; Dugravot, Aline; Valeri, Linda; Machado-Fragua, Marcos D.; Dumurgier, Julien; Kivimaki, Mika; Sabia, Severine; Singh-Manoux, Archana (2022)
    Background There is consistent evidence of social inequalities in dementia but the mechanisms underlying this association remain unclear. We examined the role of smoking in midlife in socioeconomic differences in dementia at older ages.Methods Analyses were based on 9951 (67% men) participants, median age 44.3 [IQR=39.6, 50.3] years at baseline in 1985-1988, from the Whitehall II cohort study. Socioeconomic position (SEP) and smoking (smoking status (cur-rent, ex-, never-smoker), pack years of smoking, and smoking history score (combining status and pack-years)) were measured at baseline. Counterfactual mediation analysis was used to examine the contribution of smoking to the association between SEP and dementia.Findings During a median follow-up of 31.6 (IQR 31.1, 32.6) years, 628 participants were diagnosed with dementia and 2110 died. Analyses adjusted for age, sex, ethnicity, education, and SEP showed smokers (hazard ratio [HR] 1.36 [95% CI 1.10-1.68]) but not ex-smokers (HR 0.95 [95% CI 0.79-1.14]) to have a higher risk of dementia compared to never-smokers; similar results for smoking were obtained for pack-years of smoking and smoking history score. Mediation analysis showed low SEP to be associated with higher risk of dementia (HRs between 1.97 and 2.02, depending on the measure of smoking in the model); estimate for the mediation effect was 16% for smoking status (Indirect Effect HR 1.09 [95% CI 1.03-1.15]), 7% for pack-years of smoking (Indirect Effect HR 1.03 [95% CI 1.01 -1.06]) and 11% for smoking history score (Indirect Effect HR 1.06 [95% CI 1.02-1.10]). Interpretation Our findings suggest that part of the social inequalities in dementia is mediated by smoking.Funding NIHCopyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) The Health 2022;23: Published https://doi.org/10.1016/j. lanepe.2022.100516
  • Barreto, Philipe de Souto; Maltais, Lois; Rosendahl, Erik; Vellas, Bruno; Bourdel-Marchasson, Isabelle; Lamb, Sarah E.; Pitkälä, Kaisu; Rolland, Yves (2021)
    Background: To study the effects of exercise on falls, fractures, hospitalizations, and death in people with dementia. Method: We conducted an individual-level patient data meta-analysis of 7 randomized controlled trials (RCTs). We looked for studies from the reference list of previous systematic reviews and undertook an electronic search for articles published between 2013 and 2019 in Ageline, CENTRAL, PsycINFO, PubMed, and SportsDiscus. Main (binary) outcome measures were the risk of mortality, hospitalization, faller, multiple faller, injurious faller, and fractures. Secondary (count) outcomes were the incident rates of hospitalizations, falls, and injurious falls. Results: From the 1314 participants, 771 were allocated to the exercise group and 543 to the control group. The number of cases regarding the main outcome measures in exercisers and controls were, respectively: 45 (5.8%) and 31 (5.7%) deaths; 102 (14.4%) and 65 (13.4%) participants hospitalized; 221 (34.4%) and 175 (41.3%) had at least 1 fall; 128 (20.2%) and 92 (21.7%) had multiple falls; 78 (24.8%) and 92 (29.3%) had injurious falls; and 19 (2.9%) and 15 (3.5%) had suffered a fracture. Two-step meta-analysis found no effects of exercise on any outcome. One-step meta-analysis found exercise reduced the risk of falls (odds ratio 0.75; 95% CI: 0.57-0.99). Exploratory analysis showed exercise decreased the rate of incident falls in participants with the lowest functional ability (incident rate ratio 0.48; 95% CI: 0.30-0.79). Conclusions: Although the 2-step meta-analysis suggests exercise does not have an effect on the outcomes, 1-step meta-analysis suggested that exercise may reduce fall risk. Data from further high-quality RCTs are still needed.
  • El-Khoury, Riyad; Kaulio, Eveliina; Lassila, Katariina A.; Crowther, Damian C.; Jacobs, Howard T.; Rustin, Pierre (2016)
    Mitochondrial dysfunction has been widely associated with the pathology of Alzheimer's disease, but there is no consensus on whether it is a cause or consequence of disease, nor on the precise mechanism(s). We addressed these issues by testing the effects of expressing the alternative oxidase AOX from Ciona intestinalis, in different models of AD pathology. AOX can restore respiratory electron flow when the cytochrome segment of the mitochondrial respiratory chain is inhibited, supporting ATP synthesis, maintaining cellular redox homeostasis and mitigating excess superoxide production at respiratory complexes I and III. In human HEK293-derived cells, AOX expression decreased the production of beta-amyloid peptide resulting from antimycin inhibition of respiratory complex III. Because hydrogen peroxide was neither a direct product nor substrate of AOX, the ability of AOX to mimic antioxidants in this assay must be indirect. In addition, AOX expression was able to partially alleviate the short lifespan of Drosophila models neuronally expressing human beta-amyloid peptides, whilst abrogating the induction of markers of oxidative stress. Our findings support the idea of respiratory chain dysfunction and excess ROS production as both an early step and as a pathologically meaningful target in Alzheimer's disease pathogenesis, supporting the concept of a mitochondrial vicious cycle underlying the disease. (C) 2016 The Authors. Published by Elsevier Inc.