Browsing by Subject "COGNITIVE IMPAIRMENT"

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  • Kaipainen, Aku L.; Pitkänen, Johanna; Haapalinna, Fanni; Jääskeläinen, Olli; Jokinen, Hanna; Melkas, Susanna; Erkinjuntti, Timo; Vanninen, Ritva; Koivisto, Anne M.; Lötjönen, Jyrki; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Julkunen, Valtteri (2021)
    Purpose Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial. Methods We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016. Results The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97-98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland-Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI. Conclusions MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated.
  • HATICE Grp; FINGER Grp; MAPT DSA Grp; Coley, Nicola; Ngandu, Tiia; Lehtisalo, Jenni; Soininen, Hilkka; Vellas, Bruno; Richard, Edo; Kivipelto, Miia; Andrieu, Sandrine; Laatikainen, Tiina; Strandberg, Timo (2019)
    Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
  • Kivimäki, Mika; Singh-Manoux, Archana; Batty, G. David; Sabia, Severine; Sommerlad, Andrew; Floud, Sarah; Jokela, Markus; Vahtera, Jussi; Beydoun, May A.; Suominen, Sakari B.; Koskinen, Aki; Väänänen, Ari; Goldberg, Marcel; Zins, Marie; Alfredsson, Lars; Westerholm, Peter J. M.; Knutsson, Anders; Nyberg, Solja T.; Sipilä, Pyry N.; Lindbohm, Joni V.; Pentti, Jaana; Livingston, Gill; Ferrie, Jane E.; Strandberg, Timo (2020)
    This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia. Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131x202f;415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers. Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131x202f;415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131x202f;415 participants (mean [SD] age, 43.0 [10.4] years; 80x202f;344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96x202f;591 participants with data on loss of consciousness, 10x202f;004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (= 65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of 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.
  • Akbaraly, Tasnime; Sexton, Claire; Zsoldos, Enika; Mahmood, Abda; Filippini, Nicola; Kerleau, Clarisse; Verdier, Jean-Michel; Virtanen, Marianna; Gabelle, Audrey; Ebmeier, Klaus P.; Kivimäki, Mika (2018)
    BACKGROUND: Diet quality is associated with brain aging outcomes. However, few studies have explored in humans the brain structures potentially affected by long-term diet quality. We examined whether cumulative average of the Alternative Healthy Eating Index 2010 (AHEI-2010) score during adult life (an 11-year exposure period) is associated with hippocampal volume. METHODS: Analyses were based on data from 459 participants of the Whitehall II imaging sub-study (mean age [standard deviation] (SD) = 59.6 [5.3] years in 2002-2004, 19.2% women). Multimodal magnetic resonance imaging examination was performed at the end of follow-up (2015-2016). Structural images were acquired using a high-resolution 3-dimensional T1-weighted sequence and processed with Functional Magnetic Resonance Imaging of the Brain Software Library (FSL) tools. An automated model-based segmentation and registration tool was applied to extract hippocampal volumes. RESULTS: Higher AHEI-2010 cumulative average score (reflecting long-term healthy diet quality) was associated with a larger total hippocampal volume. For each 1 SD (SD = 8.7 points) increment in AHEI-2010 score, an increase of 92.5 mm(3) (standard error = 42.0 mm(3)) in total hippocampal volume was observed. This association was independent of sociodemographic factors, smoking habits, physical activity, cardiometabolic health factors, cognitive impairment, and depressive symptoms, and was more pronounced in the left hippocampus than in the right hippocampus. Of the AHEI-2010 components, no or light alcohol consumption was independently associated with larger hippocampal volume. CONCLUSIONS: Higher long-term AHEI-2010 scores were associated with larger hippocampal volume. Accounting for the importance of hippocampal structures in several neuropsychiatric diseases, our findings reaffirm the need to consider adherence to healthy dietary recommendation in multi-interventional programs to promote healthy brain aging. (C) 2018 The Authors. 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.
  • Rajani, Rikesh M.; Ratelade, Julien; Domenga-Denier, Valerie; Hase, Yoshiki; Kalimo, Hannu; Kalaria, Raj N.; Joutel, Anne (2019)
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology ("pure" WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.
  • Jansson, A. H.; Savikko, N.; Kautiainen, H.; Roitto, H. -M.; Pitkälä, K. H. (2020)
  • Goldsteins, Gundars; Hakosalo, Vili; Jaronen, Merja; Keuters, Meike Hedwig; Lehtonen, Sarka; Koistinaho, Jari (2022)
    A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, ND have some fundamental common pathological mechanisms involving oxidative stress and neuroinflammation. The present review focuses on the major causes of central nervous system (CNS) redox homeostasis imbalance comprising mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial disturbances, leading to reduced mitochondrial function and elevated reactive oxygen species (ROS) production, are thought to be a major contributor to the pathogenesis of ND. ER dysfunction has been implicated in ND in which protein misfolding evidently causes ER stress. The consequences of ER stress ranges from an increase in ROS production to altered calcium efflux and proinflammatory signaling in glial cells. Both pathological pathways have links to ferroptotic cell death, which has been implicated to play an important role in ND. Pharmacological targeting of these pathological pathways may help alleviate or slow down neurodegeneration.
  • Claesson, Tor-björn; Putaala, Jukka; Shams, Sara; Salli, Eero; Gordin, Daniel; Liebkind, Ron; Forsblom, Carol; Summanen, Paula A.; Tatlisumak, Turgut; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2020)
    Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls. Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively. Results: Manual and automatic measurements correlated well (callosal area vs. volume: rho = 0.83, p <0.001 and mid-sagittal area vs. intracranial volume: rho = 0.82, p <0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002). Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1.
  • Perttilä, Niko M.; Öhman, Hanna; Strandberg, Timo E.; Kautiainen, Hannu; Raivio, Minna; Laakkonen, Marja-Liisa; Savikko, Niina; Tilvis, Reijo S.; Pitkälä, Kaisu H. (2018)
    Introduction No study has investigated how exercise modifies the effect of fall-related drugs (FRDs) on falls among people with Alzheimer's disease (AD). Objective The aim of this study was to investigate how exercise intervention and FRDs interact with fall risk among patients with AD. Methods In the FINALEX trial, community-dwelling persons with AD received either home-based or group-based exercise twice weekly for 1 year (n = 129); the control group received normal care (n = 65). The number of falls was based on spouses' fall diaries. We examined the incidence rate ratios (IRRs) for falls among both non-users and users of various FRDs (antihypertensives, psychotropics, drugs with anticholinergic properties [DAPs]) in both control and combined intervention groups. Results Between the intervention and control groups, there was no difference in the number of falls among those without antihypertensives or psychotropics. In the intervention group taking antihypertensives, the IRR was 0.5 falls/person-year (95% confidence interval [CI] 0.4-0.6), while in the control group, the IRR was 1.5 falls/person-year (95% CI 1.2-1.8) [p <0.001 for group, p = 0.067 for medication, p <0.001 for interaction]. Among patients using psychotropics, the intervention group had an IRR of 0.7 falls/person-year (95% CI 0.6-0.9), while the control group had an IRR of 2.0 falls/person-year (95% CI 1.6-2.5) [p <0.001 for group, p = 0.071 for medication, p <0.001 for interaction]. There was a significant difference in falls between the intervention and control groups not using DAPs (0.6, 95% CI 0.5-0.7; 1.2, 95% CI 1.0-1.4), and between the intervention and control groups using DAPs (1.1, 95% CI 0.8-1.3; 1.5, 95% CI 1.0-2.1) [p <0.001 for group, p = 0.014 for medication, p = 0.97 for interaction]. Conclusion Exercise has the potential to decrease the risk for falls among people with AD using antihypertensives and psychotropics.
  • Laakso, H. M.; Hietanen, M.; Melkas, S.; Sibolt, G.; Curtze, S.; Virta, M.; Ylikoski, R.; Pohjasvaara, T.; Kaste, M.; Erkinjuntti, T.; Jokinen, H. (2019)
    Background and purposeImpairment of executive functions (EFs) is a common cognitive symptom post-stroke and affects independence in daily activities. Previous studies have often relied on brief cognitive tests not fully considering the wide spectrum of EF subdomains. A detailed assessment of EFs was used to examine which of the subdomains and tests have the strongest predictive value on post-stroke functional outcome and institutionalization in long-term follow-up. MethodsA subsample of 62 patients from the Helsinki Stroke Aging Memory Study was evaluated with a battery of seven neuropsychological EF tests 3 months post-stroke and compared to 39 healthy control subjects. Functional impairment was evaluated with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living (IADL) scale at 3 months, and with the mRS at 15 months post-stroke. Institutionalization was reviewed from the national registers of permanent hospital admissions in up to 21-year follow-up. ResultsThe stroke group performed more poorly than the control group in multiple EF tests. Tests of inhibition, set shifting, initiation, strategy formation and processing speed were associated with the mRS and IADL scale in stroke patients. EF subdomain scores of inhibition, set shifting and processing speed were associated with functional outcome. In addition, inhibition was associated with the risk for earlier institutionalization. ConclusionsExecutive function was strongly associated with post-stroke functional impairment. In follow-up, poor inhibition was related to earlier permanent institutionalization. The results suggest the prognostic value of EF subdomains after stroke.
  • 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.
  • GBD 2016 Dementia Collaborators; Nichols, Emma; Szoeke, Cassandra E. I.; Vollset, Stein Emil; Kivimäki, Mika; Meretoja, Atte (2019)
    Background The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. Methods GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages). Findings In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages. Interpretation The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide. (C) 2018 The Author(s). Published by Elsevier Ltd.
  • Sipilä, Pyry N.; Heikkilä, Nelli; Lindbohm, Joni; Hakulinen, Christian; Vahtera, Jussi; Elovainio, Marko; Suominen, Sakari; Väänänen, Ari; Koskinen, Aki; Nyberg, Solja T.; Pentti, Jaana; Strandberg, Timo E.; Kivimäki, Mika (2021)
    Background Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods. Methods In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (>= 18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Social Support study, Dec 31, 2016, in the public sector study and the Still Working study, and Feb 7, 2018, in the replication cohort. Through record linkage to national hospital inpatient registers, we ascertained exposure to 925 infectious diseases (using the International Classification of Diseases 10th Revision codes) before dementia onset, and identified incident dementia from hospital records, medication reimbursement entitlements, and death certificates. Hazard ratios (HRs) for the associations of each infectious disease or disease group (index infection) with incident dementia were assessed by use of Cox proportional hazards models. We then repeated the analysis after excluding incident dementia cases that occurred during the first 10 years after initial hospitalisation due to the index infection. Findings From March 1, 1986, to an 1, 2005, 260 490 people were included in the primary cohort, and from Dec 19, 2006, to Oct 1, 2010, 485 708 people were included in the replication cohort. In the primary cohort analysis based on 3 947 046 person-years at risk (median follow-up 15.4 years [IQR 9- 8-21- 0]), 77108 participants had at least one hospital-treated infection before dementia onset and 2768 developed dementia. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR laHRI 1.48 [95% CI 1. 37-1- 60]) and replication cohort (2.60 [2. 38-2- 83]). The association remained when analyses were restricted to new dementia cases that occurred more than 10 years after infection (aHR 1.22 [95% CI 1.09-1.36] in the primary cohort, the replication cohort had insufficient follow-up data for this analysis), and when comorbidities and other dementia risk factors were considered. There was evidence of a dose-response association between the number of episodes of hospital-treated infections and dementia risk in both cohorts (p(trend) =0- 0007). Although the greatest dementia risk was seen for central nervous system (CNS) infections versus no infection (aHR 3.01 [95% CI 2- 07-4 center dot 37]), excess risk was also evident for extra-CNS infections (1.47 [1.36-1.59]). Although we found little difference in the infection-dementia association by type of infection, associations were stronger for vascular dementia than for Alzheimer's disease (aHR 2.09 [95% CI 1- 59-2- 75] versus aHR 1.20 [1.08-1.33] in the primary cohort and aHR 3.28 [2- 65-4 center dot 04] versus aHR 1.80 [1.53-2-13] in the replication cohort). Interpretation Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain. The absence of infection specificity combined with evidence of dose-response relationships between infectious disease burden and dementia risk support the hypothesis that increased dementia risk is driven by general inflammation rather than specific microbes. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
  • Kullberg-Turtiainen, Marjo; Vuorela, Kaisa; Huttula, Lilli; Turtiainen, Petri; Koskinen, Sanna (2019)
    Few long-term studies report late outcomes after severe traumatic brain injury. New rehabilitation techniques are needed for this heterogenous patient group. We present a dance intervention six and half years after an extreme severe TBI including excessive diffuse axonal injury, which disconnects the brain networks. Given the fact, that efficient brain function depends on the integrated operation of large-scale brain networks like default mode network (DMN), we created an intervention with multisensory and multimodal approach and goal-directed behavior. The intervention lasted four months including weekly one-hour dance lessons with the help of a physiotherapist and dance teacher. The measures included functional independence measure (FIM), repeated electroencephalogram (EEG) analysis of three subnets of DMN and clinical evaluations and observations. The results showed clear improvement after the intervention, and FIM stayed in elevated level during several years after the intervention. We present suggestion for further studies using larger patient groups.
  • Huhtaniska, Sanna; Jaaskelainen, Erika; Heikka, Tuomas; Moilanen, Jani S.; Lehtiniemi, Heli; Tohka, Jussi; Manjon, Jose V.; Coupe, Pierrick; Bjornholm, Lassi; Koponen, Hannu; Veijola, Juha; Isohanni, Matti; Kiviniemi, Vesa; Murray, Graham K.; Miettunen, Jouko (2017)
    High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning.
  • Lisboa, S. F.; Issy, A. C.; Biojone, C.; Montezuma, K.; Fattori, V.; Del-Bel, E. A.; Guimaraes, F. S.; Cunha, F. Q.; Verri, W. A.; Joca, S. R. L. (2018)
    Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse inhibition test (PPI), which provides an operational measure of sensorimotor gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion, a model predictive of antipsychotic activity; 3. resident intruder test, a model predictive of aggressive behavior. Furthermore, the animals were submitted to models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed impaired baseline PPI response, which was attenuated by D-amphetamine at a dose that did not modify PPI response in wild-type (WT) mice, suggesting a hypodopaminergic prefrontal cortex function in those mice. D-Amphetamine, however, induced hyperlocomotion in IL-18KO mice compared to their WT counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL-18KO mice presented increased basal levels of IL-1 beta levels in the hippocampus and TNF-alpha in the prefrontal cortex, suggesting an overcompensation of IL-18 absence by increased levels of other proinflammatory cytokines. Although no alteration was observed in the forced swimming or in the elevated plus maze tests in naive IL-18KO mice, these mice presented anxiogenic-like behavior after exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18 gene resembled features similar to symptoms observed in schizophrenia (positive and cognitive symptoms, aggressive behavior), in addition to increased susceptibility to stress. The IL-18KO model, therefore, could provide new insights into how changes in brain immunological homeostasis induce behavioral changes related to psychiatric disorders, such as schizophrenia.
  • Välimäki, Tarja; Koivisto, Anne; Kärkkäinen, Virve; Selander, Tuomas; Hongisto, Kristiina; Rusanen, Minna (2022)
    Objectives: Human-animal interactions have beneficial psychosocial and psychophysiological effects on individuals in both the presence and absence of medical health conditions. No previous prospective studies with long follow-up have investigated the effects of domestic pets on individuals with Alzheimer's disease (AD) who live at home. We examined the effects of pets on quality of life (QoL) and general well-being during a 5-year follow-up of home-dwelling persons with AD. Methods: In a prospective study including 223 patients with very mild (Clinical Dementia Rating Scale [CDR] 0.5) or mild (CDR 1) AD at baseline who participated in the ALSOVA study, 40 (18%) had a pet. Self- and proxy-rated QoL in AD quality of life-AD (QoL-AD), 15D, and self-rated visual analogic scale (VAS) were assessed annually for 3 years and after 5 years. The Mini-Mental State Examination, Neuropsychiatric Inventory, and CDR sum of boxes (CDR sum of boxes) were measured at the same visits. Results: A significant positive effect of pet ownership (p = 0.003, proxy-rated QoL-AD) on QoL was found over the entire follow-up. However, self-rated QoL-AD, 15D, and VAS did not significantly differ between pet owners and non-pet owners. Conclusions: The findings suggest that having a pet may support QoL in home-dwelling persons with AD. Self-rated or general QoL or well-being measurements are not an accurate method for studying QoL in individuals with dementia over time due to a lack of insight. Adding proxy-rated evaluations to this kind of study is recommended.
  • Iso-Markku, Paula; Waller, Katja; Kujala, Urho M.; Kaprio, Jaakko (2015)
    Introduction. Physical activity is associated with a decreased occurrence of dementia. In twins, we investigated the effect of persistent physical activity in adulthood on mortality due to dementia. Materials and methods. Physical activity was queried in 1975 and 1981 from the members of the older Finnish Twin Cohort (n = 2 1,791), who were aged 24-60 years at the end of 1981. The subjects were divided into three categories according to the persistence of their vigorous physical activity. Dementia deaths were followed up to the end of 2011. Results. During the 29-year follow-up, 353 subjects died of dementia. In individual-based analyses the age-and sex-adjusted hazard ratio (HR) was 0.65 (95% CI 0.43-0.98) for subjects partaking in vigorous physical activities in both 1975 and 1981 compared to those who were inactive in both years. No significant change was observed after adjusting for potential confounding factors. The corresponding HR for within-pair comparisons of the less active twin versus the more active co-twin was 0.48 (95% CI 0.17-1.32). The results for analyses of the volume of physical activity were inconclusive. Conclusions. Persistent vigorous leisure-time physical activity protects from dementia, and the effect appears to remain after taking into account childhood environment.