Publications by authors named "Raimo Sulkava"

101 Publications

Melatonin receptor type 1A gene linked to Alzheimer's disease in old age.

Sleep 2018 07;41(7)

Department of Health, Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.

Disruption of the circadian rhythms is a frequent preclinical and clinical manifestation of Alzheimer's disease. Furthermore, it has been suggested that shift work is a risk factor for Alzheimer's disease. Previously, we have reported association of intolerance to shift work (job-related exhaustion in shift workers) with a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A) and linked to MTNR1A brain expression levels. Here, we studied association of that variant with clinical and neuropathological Alzheimer's disease in a Finnish whole-population cohort Vantaa 85+ (n = 512, participants over 85 years) and two follow-up cohorts. Rs12506228A was associated with clinical Alzheimer's disease (p = 0.000073). Analysis of post-mortem brain tissues showed association with higher amount of neurofibrillary tangles (p = 0.0039) and amyloid beta plaques (p = 0.0041). We then followed up the associations in two independent replication samples. Replication for the association with clinical Alzheimer's disease was detected in Kuopio 75+ (p = 0.012, n = 574), but not in the younger case-control sample (n = 651 + 669). While melatonin has been established in regulation of circadian rhythms, an independent role has been also shown for neuroprotection and specifically for anti-amyloidogenic effects. Indeed, in vitro, RNAi mediated silencing of MTNR1A increased the amyloidogenic processing of amyloid precursor protein (APP) in neurons, whereas overexpression decreased it. Our findings suggest variation close to MTNR1A as a shared genetic risk factor for intolerance to shift work and Alzheimer's disease in old age. The genetic associations are likely to be mediated by differences in MTNR1A expression, which, in turn, modulate APP metabolism.
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http://dx.doi.org/10.1093/sleep/zsy103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047434PMC
July 2018

Insulin Resistance Predicts Cognitive Decline: An 11-Year Follow-up of a Nationally Representative Adult Population Sample.

Diabetes Care 2017 06 5;40(6):751-758. Epub 2017 Apr 5.

National Institute for Health and Welfare, Turku, Finland.

Objective: The aim of this study was to examine whether insulin resistance, assessed by HOMA of insulin resistance (HOMA-IR), is an independent predictor of cognitive decline.

Research Design And Methods: The roles of HOMA-IR, fasting insulin and glucose, HbA, and hs-CRP as predictors of cognitive performance and its change were evaluated in the Finnish nationwide, population-based Health 2000 Health Examination Survey and its 11-year follow-up, the Health 2011 study ( = 3,695, mean age at baseline 49.3 years, 55.5% women). Categorical verbal fluency, word-list learning, and word-list delayed recall were used as measures of cognitive function. Multivariate linear regression analysis was performed and adjusted for previously reported risk factors for cognitive decline.

Results: Higher baseline HOMA-IR and fasting insulin levels were independent predictors of poorer verbal fluency performance ( = 0.0002 for both) and of a greater decline in verbal fluency during the follow-up time ( = 0.004 for both). Baseline HOMA-IR and insulin did not predict word-list learning or word-list delayed recall scores. There were no interactions between HOMA-IR and apolipoprotein E ε4 () genotype, hs-CRP, or type 2 diabetes on the cognitive tests. Fasting glucose and hs-CRP levels at baseline were not associated with cognitive functioning.

Conclusions: Our results show that higher serum fasting insulin and insulin resistance predict poorer verbal fluency and a steeper decline in verbal fluency during 11 years in a representative sample of an adult population. Prevention and treatment of insulin resistance might help reduce cognitive decline later in life.
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http://dx.doi.org/10.2337/dc16-2001DOI Listing
June 2017

Common Genetic Variation Near Melatonin Receptor 1A Gene Linked to Job-Related Exhaustion in Shift Workers.

Sleep 2017 Jan;40(1)

Department of Health, Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.

Study Objectives: Tolerance to shift work varies; only some shift workers suffer from disturbed sleep, fatigue, and job-related exhaustion. Our aim was to explore molecular genetic risk factors for intolerance to shift work.

Methods: We assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey, and carried out a genome-wide association study (GWAS) using Illumina's Human610-Quad BeadChip (n = 176). The most significant findings were further studied in three groups of Finnish shift workers (n = 577). We assessed methylation in blood cells with the Illumina HumanMethylation450K BeadChip, and examined gene expression levels in the publicly available eGWAS Mayo data.

Results: The second strongest signal identified in the GWAS (p = 2.3 × 10E-6) was replicated in two of the replication studies with p < .05 (p = 2.0 × 10E-4 when combining the replication studies) and indicated an association of job-related exhaustion in shift workers with rs12506228, located downstream of the melatonin receptor 1A gene (MTNR1A). The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and suggestively associated with changes in DNA methylation in the 5' regulatory region of MTNR1A.

Conclusions: These findings suggest that a variant near MTNR1A may be associated with job-related exhaustion in shift workers. The risk variant may exert its effect via epigenetic mechanisms, potentially leading to reduced melatonin signaling in the brain. These results could indicate a link between melatonin signaling, a key circadian regulatory mechanism, and tolerance to shift work.
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http://dx.doi.org/10.1093/sleep/zsw011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806557PMC
January 2017

Genome-wide association study of neocortical Lewy-related pathology.

Ann Clin Transl Neurol 2015 Sep 18;2(9):920-31. Epub 2015 Aug 18.

Molecular Neurology, Research Program Unit, Biomedicum, University of Helsinki Helsinki, Finland ; Department of Neurology, Helsinki University Central Hospital Helsinki, Finland.

Objective: Dementia with Lewy bodies is an α-synucleinopathy characterized by neocortical Lewy-related pathology (LRP). We carried out a genome-wide association study (GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over.

Methods: LRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study (CFAS) material was used for replication (51 cases and 131 controls).

Results: By analyzing 327,010 markers the top signal was obtained at the HLA-DPA1/DPB1 locus (P = 1.29 × 10(-7)); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10(-5). Two loci were marked by multiple markers, 2p21 (P = 3.9 × 10(-6), upstream of the SPTBN1 gene), and HLA-DPA1/DPB1; these were tested in the CFAS material. Single marker (P = 0.0035) and haplotype (P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA-DPA1/DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA-DPA1/DPB1 markers as well as the 15q14 marker rs8037309.

Interpretation: We identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an α-synuclein binding protein and a component of Lewy bodies. The HLA-DPA1/DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with α-synuclein in a yeast model.
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http://dx.doi.org/10.1002/acn3.231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574809PMC
September 2015

Insulin resistance is associated with poorer verbal fluency performance in women.

Diabetologia 2015 Nov 15;58(11):2545-53. Epub 2015 Aug 15.

National Institute for Health and Welfare (THL), Turku, Finland.

Aims/hypothesis: Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association.

Methods: The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests.

Results: Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02).

Conclusions/interpretation: To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.
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http://dx.doi.org/10.1007/s00125-015-3715-4DOI Listing
November 2015

Impact of missing data mechanism on the estimate of change: a case study on cognitive function and polypharmacy among older persons.

Clin Epidemiol 2015 4;7:169-80. Epub 2015 Feb 4.

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.

Longitudinal studies typically suffer from incompleteness of data. Attrition is a major problem in studies of older persons since participants may die during the study or are too frail to participate in follow-up examinations. Attrition is typically related to an individual's health; therefore, ignoring it may lead to too optimistic inferences, for example, about cognitive decline or changes in polypharmacy. The objective of this study is to compare the estimates of level and slope of change in 1) cognitive function and 2) number of drugs in use between the assumptions of ignorable and non-ignorable missingness. This study demonstrates the usefulness of latent variable modeling framework. The results suggest that when the missing data mechanism is not known, it is preferable to conduct analyses both under ignorable and non-ignorable missing data assumptions.
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http://dx.doi.org/10.2147/CLEP.S72918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323142PMC
February 2015

Use of antidepressants among community-dwelling persons with Alzheimer's disease: a nationwide register-based study.

Int Psychogeriatr 2015 Apr 21;27(4):669-72. Epub 2014 Nov 21.

Kuopio Research Centre of Geriatric Care,University of Eastern Finland,Kuopio,Finland.

Background: Antidepressants are used to treat depression and behavioral symptoms in Alzheimer's disease (AD), although their effectiveness has been questioned and evidence about the risks is accumulating. The objective of this study was to compare antidepressant use among persons with and without AD in Finland.

Methods: The Social Insurance Institution of Finland (SII) identified all persons with a verified diagnosis of AD in Finland on December 31, 2005. For each person with AD a comparison person matched for age, sex and region of residence was also identified. Data on reimbursed drug purchases in 2005 were extracted from the Finnish National Prescription Register (FNPR). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for antidepressant use.

Results: The study sample comprised of 28,089 matched pairs of persons with and without AD (mean age 80.0 SD 6.8, 32.2% men).The prevalence of antidepressant use was higher among persons with AD than without AD (29.4% vs. 10.7%, OR = 3.54; 95% CI: 3.38, 3.70). Among the persons with AD, the prevalence of antidepressant use increased with time since AD diagnosis but not with age. Overall, 90.4% of antidepressant users with AD were co-dispensed anti-dementia drugs.

Conclusions: The antidepressant use was three times more prevalent among persons with AD compared to those without. Though the antidepressant selection was largely consistent with clinical practice guidelines, the high prevalence of use warrants further investigation given the uncertain effectiveness and adverse events related to these drugs.
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http://dx.doi.org/10.1017/S1041610214002427DOI Listing
April 2015

Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium.

Am J Geriatr Psychiatry 2015 Apr 15;23(4):403-415. Epub 2014 Aug 15.

Trinity College Institute of Neuroscience, School of Biochemistry and Immunology, Trinity College Dublin, Republic of Ireland. Electronic address:

Background: Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk.

Methods: Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry.

Results: In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology.

Conclusion: A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology.
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http://dx.doi.org/10.1016/j.jagp.2014.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278840PMC
April 2015

Depressive symptoms and cardiovascular burden-related mortality among the aged.

Eur J Clin Invest 2014 May;44(5):486-92

Department of Clinical Neurophysiology, Helsinki University Central Hospital, Helsinki, Finland; Department of Internal Medicine, Lahti, Finland.

Background: Depressive symptoms have been linked to increased cardiovascular mortality among the elderly. This study was aimed to test the independent and additive predictive value of depressive symptoms and B-type natriuretic peptide (BNP), a marker of direct cardiovascular stress and a strong predictor of mortality, together with traditional cardiovascular risk markers on total and cardiovascular mortalities in a general elderly population.

Methods: A total of 508 subjects aged 75 or older participated in the study. The prognostic capacity of depressive symptoms and BNP in regard to total and cardiovascular mortalities was assessed with Cox regression analyses. Depressive symptoms were handled as a dichotomous variable based on the Zung self-rated depression scale score with a cut-off point of 40.

Results: The median follow-up time was 84 months with an interquartile range of 36-99 months. Depressive symptoms reflected susceptibility to all-cause (HR 1·60; 95% CI 1·26-2·04) and cardiovascular mortalities (HR 1·81; 95% CI 1·30-2·52) only in univariable analyses. When cardiovascular illnesses and risk markers were taken into account, depressive symptoms lost their significance as an independent predictor of mortality. BNP as a continuous variable was a significant predictor of both all-cause (HR 1·44; 95% CI 1·22-1·69) and cardiovascular mortalities (HR 1·79; 95% CI 1·44-2·22) in fully adjusted models including depressive symptoms as a covariate.

Conclusions: The prognostic capacity of depressive symptoms is closely linked to cardiovascular morbidity and has no independent power in an elderly general population. BNP remains a strong harbinger of death regardless of depressive symptoms status.
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http://dx.doi.org/10.1111/eci.12262DOI Listing
May 2014

Effects of comprehensive geriatric assessment-based individually targeted interventions on mobility of pre-frail and frail community-dwelling older people.

Geriatr Gerontol Int 2015 Jan 8;15(1):80-8. Epub 2014 Jan 8.

Social and Health Services, City of Kuopio, Kuopio, Finland; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Institute of Public Health and Clinical Nutrition, Department of Public Health, University of Eastern Finland, Kuopio, Finland.

Aim: To assess the effects of comprehensive geriatric assessment (CGA)-based individually targeted interventions on the ability to walk 400 m in pre-frail or frail and non-frail community-dwelling older people.

Methods: A subgroups analysis of a population-based comparative study, the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) was carried out in the city of Kuopio, Finland, from 2004 to 2007. This study was based on data from 2005 to 2007. The present analysis included 605 community-dwelling older adults aged ≥ 76 years (mean age 80.9, 70% women), 314 in the intervention and 291 in the control group. Frailty status was assessed in 2005. Mobility was assessed by self-reported ability to walk 400 m. The generalized estimating equation model with binary logistic regression was used to assess the treatment effect of the interventions on the ability to walk 400 m between 2005 and 2007.

Results: In 2005, 55% (n = 173) of the participants in the intervention group and 64% (n = 187) in the control group were pre-frail or frail. The intervention prevented the loss of ability to walk 400 m among pre-frail and frail persons (OR 0.74, 95% CI 0.59-0.93, P = 0.01). The treatment effect was not statistically significant among non-frail participants (OR 0.99, 95% CI 0.68-1.42, P = 0.94).

Conclusions: CGA-based individually targeted interventions were effective in preventing mobility limitations among pre-frail and frail older people.
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http://dx.doi.org/10.1111/ggi.12231DOI Listing
January 2015

Determinants for preventive oral health care need among community-dwelling older people: a population-based study.

Spec Care Dentist 2014 Jan-Feb;34(1):19-26. Epub 2013 Feb 28.

Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland; Clinical Pharmacology and Geriatric Pharmacotherapy Unit, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Social and Health Centre of Kuopio, Finland.

The aim was to study the determinants of preventive oral health care need among community-dwelling old people. The study population consisted of 165 participants, a subpopulation in the Geriatric Multidisciplinary Strategy for Good Care of Elderly People (GeMS) study. Fifty-five percent of the edentate participants with full dentures and 82% of the dentate had a need for preventive oral health care. In the total study population, the need for preventive care was associated with co-morbidity (measured by means of the Modified Functional Co-morbidity Index) odds ratios (OR) 1.2 (confidence intervals [CI] 1.0-1.5), being pre-frail or frail, OR 2.5 (CI 1.2-5.1), presence of natural teeth, OR 4.8 (CI 2.2-10.4), and among dentate participants, the use of a removable partial denture, OR 12.8 (CI 1.4-114.4). Primary care clinicians should be aware of the high need for preventive care and the importance of nonoral conditions as determinants of preventive oral health care need.
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http://dx.doi.org/10.1111/scd.12021DOI Listing
October 2015

B-type natriuretic peptide and severity of cognitive disorder.

Eur J Clin Invest 2013 Nov 17;43(11):1171-7. Epub 2013 Sep 17.

Department of Clinical Neurophysiology, Helsinki University Central Hospital, Helsinki, Finland; Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland.

Background: Natriuretic peptides have been linked to cognitive disorder in previous studies. The aim of this study was to examine the association between the severity of cognitive disorder and the levels of B-type natriuretic peptide (BNP) in an older general population.

Material And Methods: This study is a part of the larger population-based, multidisciplinary Kuopio 75+ health study. A total of 601 subjects aged 75 or older participated in the study. A subgroup of 126 individuals was diagnosed with cognitive disorder, and the severity of the disease was assessed. The participants were tested for BNP. Analysis of covariance was carried out to study the relationship between BNP and the stage of cognitive disorder.

Results: The association between the level of cognitive disorder and BNP resembled an inverse U-shaped curve, with higher levels of BNP observed among participants with mild cognitive disorder when compared to cognitively intact participants or counterparts with more severe cognitive disorder. This effect remained after adjustment for age (P = 0.02). However, association between BNP and level of cognitive disorder was lost in further adjustment with covariates connected to the levels of BNP.

Conclusion: The previously reported elevation of natriuretic peptides among individuals with diagnosed cognitive disorder was found only in people with milder stages of the disorder.
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http://dx.doi.org/10.1111/eci.12160DOI Listing
November 2013

Relationship between functional vision and balance and mobility performance in community-dwelling older adults.

Aging Clin Exp Res 2013 Oct 4;25(5):545-52. Epub 2013 Sep 4.

Department of Health Sciences, University of Jyväskylä, P.O. Box 35 (LL), FIN 40014, Jyväskylä, Finland,

Background And Aims: Vision is an important prerequisite for balance control and mobility. The role of objectively measured visual functions has been previously studied but less is known about associations of functional vision, that refers to self-perceived vision-based ability to perform daily activities. The aim of the study was to investigate the relationship between functional vision and balance and mobility performance in a community-based sample of older adults.

Methods: This study is part of a Geriatric Multidisciplinary Strategy for the Good Care of the Elderly project (GeMS). Participants (576) aged 76-100 years (mean age 81 years, 70 % women) were interviewed using a seven-item functional vision questionnaire (VF-7). Balance and mobility were measured by the Berg balance scale (BBS), timed up and go (TUG), chair stand test, and maximal walking speed. In addition, self-reported fear of falling, depressive symptoms (15-item Geriatric Depression Scale), cognition (Mini-Mental State Examination) and physical activity (Grimby) were assessed. In the analysis, participants were classified into poor, moderate, or good functional vision groups.

Results: The poor functional vision group (n = 95) had more comorbidities, depressed mood, cognition decline, fear of falling, and reduced physical activity compared to participants with moderate (n = 222) or good functional vision (n = 259). Participants with poor functional vision performed worse on all balance and mobility tests. After adjusting for gender, age, chronic conditions, and cognition, the linearity remained statistically significant between functional vision and BBS (p = 0.013), TUG (p = 0.010), and maximal walking speed (p = 0.008), but not between functional vision and chair stand (p = 0.069).

Conclusion: Poor functional vision is related to weaker balance and mobility performance in community-dwelling older adults. This highlights the importance of widespread assessment of health, including functional vision, to prevent balance impairment and maintain independent mobility among older population.
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http://dx.doi.org/10.1007/s40520-013-0120-zDOI Listing
October 2013

Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study.

Brain 2013 Sep;136(Pt 9):2707-16

Ageing Research Centre, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, 11330 Stockholm, Sweden.

Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged ≥85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-β and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and α-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-β accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or α-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged ≥85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.
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http://dx.doi.org/10.1093/brain/awt206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754457PMC
September 2013

Oral health intervention among community-dwelling older people: a randomised 2-year intervention study.

Gerodontology 2015 Mar 10;32(1):62-72. Epub 2013 Jul 10.

Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland; Clinical Pharmacology and Geriatric Pharmacotherapy Unit, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Social and Health Centre of Kuopio, Kuopio, Finland.

Objective: The aim of this study was to investigate the effects of a 2-year oral-health-promoting intervention on oral health behaviour and oral health among people aged 75 years or older.

Materials And Methods: In a 2-year randomised intervention study, 279 community-dwelling older people completed the study: 145 persons in an intervention group and 134 in a control group. Interviews and clinical oral examinations were performed at the beginning of the study and at a 2-year follow-up. Changes in oral health behaviour and oral health were used as outcomes.

Intervention: Oral health intervention included individually tailored instructions for oral and/or denture hygiene, relief of dry mouth symptoms, decrease of sugar-use frequency, use of fluoride, xylitol or antimicrobial products, and professional tooth cleaning.

Results: More participants in both the intervention and control groups had better dental and denture hygiene and were free of oral diseases or symptoms at the 2-year follow-up than at the baseline. The differences in changes in outcomes between the intervention and control groups were not statistically significant.

Conclusion: The results of this study showed that oral health of community-dwelling older people could be improved. Oral health improved in both groups, more among the participants in the intervention group compared with control group, but the effect attributed to oral-health-promoting intervention remained small.
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http://dx.doi.org/10.1111/ger.12067DOI Listing
March 2015

Effects of comprehensive health assessment and targeted intervention on chair rise capacity in active and inactive community-dwelling older people.

Gerontology 2013 21;59(4):324-7. Epub 2013 Mar 21.

Social and Health Services, City of Kuopio, Kuopio, Finland.

Background: Being able to rise from a chair is an important daily life activity that requires sufficient lower extremity muscle power and postural control.

Objective: To assess the effects of an individually tailored intervention on the chair rise capacity of active and inactive community-dwelling older men and women.

Methods: This study included a community-based sample of ≥75-year-olds who were randomized into intervention (n = 299) and control (n = 260) groups. The intervention started in 2004 and ended in December 2006; all the participants of the intervention group received individually targeted physical activity counseling annually and had an opportunity to participate in supervised strength and balance training once a week. Chair rise tests were conducted annually. The mixed model of linear regression was used for unadjusted measurements and age, and the Mini-Mental State Examination and functional comorbidity index adjusted comparisons of effects of the intervention.

Results: The intervention improved the chair rise capacity in physically active women (adjusted mean difference -1.67 s, 95% confidence interval -3.21 to -0.13, p = 0.02). There was no improvement in inactive women or in men, regardless of their physical activity level.

Conclusion: Intervention showed a positive effect on the chair rise capacity of physically active community-dwelling older women.
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http://dx.doi.org/10.1159/000347197DOI Listing
February 2014

Effects of comprehensive geriatric intervention on physical performance among people aged 75 years and over.

Aging Clin Exp Res 2012 Aug;24(4):331-8

Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Background And Aims: We studied the effects of comprehensive geriatric assessment and multifactorial intervention on physical performance among older people.

Methods: In a 3-year geriatric development project with an experimental design, 668 participants aged 75-98 were assigned to intervention (n=348) or control (n=320) groups. The intervention group received comprehensive geriatric assessment with an individually targeted intervention for 2 years. The outcome measures - performance in the Timed Up-and-Go (TUG), 10-meter walking and Berg Balance Scale tests - were gathered annually during the intervention and the 1-year follow-up after it.

Results: With linear mixed models, over the 2-year intervention period, the intervention group was found to be improved in the balance (p<0.001) and walking speed (p<0.001) tests, and maintained performance in the TUG test (p<0.001), compared with the control group. The results remained significant 1 year post-intervention.

Conclusions: Comprehensive geriatric assessment and individually targeted multifactorial intervention had positive effects on physical performance, potentially helping to maintain mobility and prevent disability in old age.
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http://dx.doi.org/10.1007/BF03325264DOI Listing
August 2012

Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population.

Neurobiol Aging 2013 May 24;34(5):1518.e1-3. Epub 2012 Oct 24.

Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.

Pathogenic mutations of the APP gene, leading to early-onset Alzheimer's disease (AD) have been known for more than 20 years. Recently, it was discovered that APP mutations might also be protective. A rare variant A673T reportedly protects against AD and age-related cognitive impairment and might functionally inhibit proteolytic cleavage at the β-secretase site of APP. We sequenced APP exon 16 in a population-based sample of 515 Finnish subjects aged 85 or older. Neuropathologic data were available in 274. We found the A673T variant in 1 subject (0.2%), who lived until age 104.8 years (second highest age-at-death in the cohort). Neuropathologic analysis showed little beta-amyloid pathology (Consortium to Establish a Registry for Alzheimer's Disease score 0). Some vascular amyloid was detected in meningeal arteries suggesting that vascular β-amyloid accumulation might be less inhibited than the parenchymal. She was demented at the age of 104, most likely because of hippocampal sclerosis. The low amount of parenchymal β-amyloid pathology at the age of 104.8 years supports the concept that the A673T variant protects the brain against β-amyloid pathology and AD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2012.09.017DOI Listing
May 2013

Intracerebral hemorrhage in the oldest old: a population-based study (vantaa 85+).

Front Neurol 2012 28;3:103. Epub 2012 Jun 28.

Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB Helsinki, Finland.

Aims: Very elderly subjects represent the fastest growing population in the world. Most of the recent studies on intracerebral hemorrhage (ICH) have been carried out on younger patients and/or preferably using novel radiological techniques. We investigated the prevalence, risk factors, and histopathological characteristics of the ICH in the oldest old.

Materials And Methods: The brains of 300 autopsied individuals (248 females, 52 males, mean age at death 92.4 ± 3.7 years) were investigated as part of the prospective population-based Vantaa 85+ study. After macroscopic investigation, the presence and extent of microscopic brain hemorrhages (MH) were analyzed by counting the number of iron containing macrophages (siderophages) by Prussian blue staining. Deposits with >5 siderophages were defined as MH+, forming a subgroup of MH. Genotyping of apolipoprotein E (APOE) and the analysis of microscopic (MI) or larger infarctions and cerebral amyloid angiopathy (CAA) were performed using standardized methods. Regression analysis was used to predict the presence of ICH, with and without co-localized CAA, and was adjusted for age at death and gender.

Results: The prevalence of macroscopic ICH was 2.3% in total; consisting of 1% large lobar hemorrhage (LH), 1% deep hemorrhage (DH), and 0.3% of subarachnoid hemorrhage (SAH). 62% had MH and 15.3% MH+. All MH+ lesions were found to be >2 mm wide. 55.9% of subjects with MH and 81.2% of those with MH+ showed MH/MH+ and CAA in the same brain region (MHCAA and MH+CAA, respectively). MH was associated with none of the neuropathological or clinical conditions, nor with the APOE carrier status. The subjects with MH+, MHCAA or MH+CAA carried the APOE ε4 allele more frequently than controls (OR 3.681, 3.291, 7.522, respectively). Siderophages in MH+CAA co-localized with CAA and with two-thirds of the MI in the tissue sections.

Conclusion: Macroscopic ICH was rare in the very elderly. MH was frequent and clinically insignificant. MH+ was rare but closely related with the APOE ε4 genotype and the presence of severe CAA and infarction.
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http://dx.doi.org/10.3389/fneur.2012.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449495PMC
October 2012

Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study.

Brain 2012 Sep 9;135(Pt 9):2809-16. Epub 2012 Aug 9.

Department of Public Health and Primary Care, University of Cambridge, UK.

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1-35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5-6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4-5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11-1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1-3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2-6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ε status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia.
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http://dx.doi.org/10.1093/brain/aws190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437024PMC
September 2012

The prognostic capacity of B-type natriuretic peptide on cognitive disorder varies by age.

Ann Med 2013 Feb 11;45(1):74-8. Epub 2012 Jun 11.

Department of Clinical Neurophysiology, Helsinki University Central Hospital, FI-00290 Helsinki, Finland.

Introduction: It is known that blood levels of natriuretic peptides associate with cognitive disorder among the middle-aged. We aimed to test whether this association is valid in an older population aged 75 years or older.

Methods: A total of 601 older subjects aged 75 or older participated in the study. A subgroup of 137 with a diagnosed cognitive disorder were tested for natriuretic peptides (ANP, NT-proANP, and BNP), and compared with age-matched controls (n = 464). The control group was followed-up for 5 years, and the association of the baseline BNP with the occurrence of cognitive impairment was studied.

Results: In the youngest age tertile (75-78 y), BNP was significantly associated with a diagnosed cognitive disorder when other factors with a known effect on natriuretic peptides were taken into account. In the oldest tertile (83-96 y), higher BNP values suggested the absence of cognitive dysfunction. ANP and NT-proANP did not associate with the presence of cognitive impairment. Among the control group, BNP predicted a cognitive disorder at follow-up, but only in the youngest tertile.

Conclusions: The previously found link between a high BNP concentration and cognitive disorder in older people is only valid among those aged less than 79 years.
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http://dx.doi.org/10.3109/07853890.2012.663929DOI Listing
February 2013

Salivary flow rate and risk of malnutrition - a study among dentate, community-dwelling older people.

Gerodontology 2013 Dec 14;30(4):270-5. Epub 2012 May 14.

Department of Periodontology, Institute of Dentistry, University of Oulu, Oulu, FinlandFinnish Student Health Service, Jyväskylä, FinlandKuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, FinlandSocial and Health Centre of Kuopio, Kuopio, FinlandUnit of Clinical Pharmacology and Geriatric Pharmacotherapy, Kuopio Research Centre for Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, FinlandInstitute of Dentistry, University of Oulu, Oulu, FinlandLeppävirta Health Centre, Leppävirta, FinlandDepartment of Geriatrics, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, FinlandDepartment of Neurology, Kuopio University Hospital, Kuopio, FinlandInstitute of Dentistry, University of Eastern finland, Kuopio, Finland.

Objective: To analyse the relation between unstimulated and stimulated salivary secretion and the risk of malnutrition among home-dwelling elderly people.

Background: Saliva has an important role in eating. Despite this, there are only a few studies on the role of salivary secretion in the development of malnutrition among elderly people.

Materials And Methods: The study population consisted of 157 subjects aged 75 or older. This was a part of GeMS study carried out in Kuopio, in eastern Finland. The data used in this study were collected by means of interviews and geriatric and oral clinical examinations. The risk of malnutrition was measured using the Mini Nutritional Assessment Short-Form. Logistic regression models were used to estimate odds ratios (OR) and their 95% Confidence Intervals (CI).

Results: Subjects with a low unstimulated salivary flow rate (<0.1 ml/min) or stimulated salivary flow rate (<1.0 ml/min) had no statistically significant increase in risk of malnutrition, OR: 1.3, CI: 0.5-3.9, OR: 1.5, CI: 0.5-4.2, respectively, when compared with those with a normal unstimulated and stimulated salivary flow rate.

Conclusion: Our results do not support the concept that low salivary secretion is an important risk factor for malnutrition among community-dwelling elders.
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http://dx.doi.org/10.1111/j.1741-2358.2012.00679.xDOI Listing
December 2013

Nutritional screening in a population-based cohort of community-dwelling older people.

Eur J Public Health 2013 Jun 25;23(3):405-9. Epub 2012 Apr 25.

Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.

Background: The risk of malnutrition is widely recognized in institutional settings but few studies have been conducted among community-dwelling older people. The objective of this study was to describe the nutritional status and factors associated with possible malnutrition among community-dwelling older people.

Methods: A randomly selected sample (n = 696) of persons aged ≥ 75 years were included in the study. Baseline information was obtained for nutritional status (mini nutritional assessment short-form MNA-SF), depressive symptoms (15-item geriatric depression scale), cognitive status (mini-mental state examination MMSE) and daily activities (Barthel ADL index and Lawton and Brody IADL scale), self-reported health, oral health and medication use. Univariate and multivariate regression analyses were conducted to identify demographical, clinical and functional factors associated with possible malnutrition.

Results: Of the 696 participants, 15% had possible malnutrition. In the univariate analysis, low MNA-SF scores were associated with advanced age, poor self-rated health, dry mouth/chewing problems, depressive symptoms and an increasing number of drugs in regular use. Higher albumin level, ADL, IADL and MMSE scores, and the ability to walk 400 m independently were inversely associated with possible malnutrition. In the multivariate analysis, dry mouth/chewing problems (OR 2.01, 95% CI: 1.14-3.54), IADL (OR 0.85, 95% CI: 0.75-0.96) and MMSE scores (OR 0.90, 95% 0.85-0.96) were independently associated with possible malnutrition.

Conclusion: Being at risk of malnutrition was common among community-dwelling older people. Problems with mouth, IADL and cognitive impairments were linked to possible nutritional risks.
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http://dx.doi.org/10.1093/eurpub/cks026DOI Listing
June 2013

Drug Burden Index and hospitalization among community-dwelling older people.

Drugs Aging 2012 May;29(5):395-404

Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.

Background: Medications with anticholinergic and sedative effects carry significant risks in older people. Adverse events arising from the use of these medications may also lead to hospitalization and contribute to length of stay. The Drug Burden Index (DBI) is a tool that measures a person's total exposure to medications with anticholinergic and sedative properties, using the principles of dose response and maximal effect. Cumulative anticholinergic and sedative drug burden measured using the DBI has been associated with clinically important outcomes in older people. The association between the DBI and hospitalization still remains relatively unknown.

Objective: The main aim of this study was to evaluate the relationship between DBI and hospitalization in a population-based sample of community-dwelling older Finns over a 1-year period.

Methods: The health status and medication use of 339 community-dwelling ≥75-year-old Finns were assessed in 2004. Data on hospitalizations over the following year were obtained from the national discharge register. Two different measures were used to assess hospitalizations in the study sample: (i) the proportion of hospitalized participants; and (ii) the number of hospital days per person-year. Estimates for the number of hospital days per person-year and rate ratios (RRs) with 95% confidence intervals (CIs) were calculated using Poisson or negative binomial regression analysis.

Results: A total of 127 participants (38%) were exposed to DBI medications; 27% had a low DBI (>0 to <1), and 11% had a high DBI (≥1). The number of hospital days per person-year was 7.9 (95% CI 7.6, 8.3) for the unexposed participants (DBI = 0) and 13.4 (95% CI 12.8, 14.1) for the exposed participants (DBI >1); the age, gender and co-morbidity adjusted RR of hospital days per person-year between the exposed and unexposed participants was 1.26 (95% CI 1.18, 1.35). Between the low and high DBI groups, the difference in the number of hospital days per person-year was insignificant (p = 0.42). In multivariate analyses, the number of regularly used medications (RR = 1.12 [95% CI 1.00, 1.26] per additional medication) and the measure of basic activities of daily living Barthel Index (RR = 0.94 [95% CI 0.88, 0.99] per increase) were independently associated with the use of hospital days.

Conclusion: Exposure to DBI medications was associated with a greater use of hospital days, but a cumulative dose-response relationship between DBI and hospitalization was not observed. The number of regularly used medications and functioning in the basic activities of daily living predicted hospital care utilization.
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http://dx.doi.org/10.2165/11631420-000000000-00000DOI Listing
May 2012

Physical activity at age of 20-64 years and mobility and muscle strength in old age: a community-based study.

J Gerontol A Biol Sci Med Sci 2012 Aug 6;67(8):905-10. Epub 2012 Mar 6.

Institute of Public Health and Clinical Nutrition, Department of Public Health, University of Eastern Finland, Kuopio, Finland.

Background: Physical activity in midlife has been related to lower mortality and better health in old age. The present study evaluated whether physical activity at age of 20-64 years was associated with mobility and muscle strength in old age.

Methods: A random sample of 1,000 persons was extracted from all the ≥75-year-old people living in Kuopio, Finland, and 679 community-dwelling participants were included in the present analyses. Data on health status, ability to walk outside or 400 m, and physical activity level were obtained through structured interviews. Participants' walking speed, grip strength, and knee extension strength were measured by physiotherapists. Relationship between physical activity at age of 20-64 years and old-age mobility and strength was assessed using logistic regression and covariance analyses.

Results: Of the 679 participants (mean age 80.8 years), 58.8% had been physically active at age of 20-64 years. Physical activity at that age was positively associated with ability to walk 400 m independently in old age (adjusted odds ratio 2.17, 95% confidence intervals: 1.25-3.77). Men who had been physically active at age of 20-64 years had greater walking speed (adjusted p = .01) and grip strength (adjusted p = .02) compared with physically inactive men. In women, the results did not differ statistically significantly.

Conclusions: Physical activity at age of 20-64 years was associated with better mobility in old age. It was also linked to better grip strength and walking speed in older men but not in women.
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http://dx.doi.org/10.1093/gerona/gls005DOI Listing
August 2012

Sedative load among community-dwelling people aged 75 years or older: association with balance and mobility.

J Clin Psychopharmacol 2012 Apr;32(2):218-24

Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.

Drugs with sedative properties are frequently used among older people. Sedative load is a measure of the cumulative effect of taking multiple drugs with sedative properties. The objective of this study was to investigate the association between sedative load and balance and mobility. A random sample of 1000 people 75 years or older was invited to participate. Seven hundred community-dwelling participants (mean age, 81.3 years; 69% women) were included in the present study. Demographic, diagnostic, and drug use data were elicited during nurse interviews in 2004. Balance and mobility were tested by physiotherapists. Sedative load was calculated using a previously published model for each participant by summing the sedative ratings of primary sedatives (rating 2) and drugs with sedation as a prominent adverse effect (rating 1). Analyses of covariance and logistic regression analyses were used to assess the association between sedative load and balance and mobility. Of the 700 participants, 21% (n = 147) had a sedative load of 1-2, and 8% (n = 58) had sedative load of 3 or greater. After adjusting for covariates, exposure to higher sedative load ranges was associated with slower walking speed (P = 0.0003), longer time to perform Timed Up and Go test (P = 0.005), and lower scores on Berg Balance Scale (P = 0.005), but not with self-reported ability to walk 400 m. In conclusion, having a higher sedative load was associated with impaired balance and mobility among community-dwelling older people. Clinicians should remain cognizant of this association and regularly reevaluate drug therapy prescribed to older people.
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http://dx.doi.org/10.1097/JCP.0b013e3182485802DOI Listing
April 2012

Associations of instrumental activities of daily living and handgrip strength with oral self-care among home-dwelling elderly 75+.

Gerodontology 2012 Jun 12;29(2):e135-42. Epub 2012 Jan 12.

Kuopio Research Centre of Geriatric Care, Unit of Clinical Pharmacology and Geriatric Pharmacotherapy, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Objective: To study the associations of instrumental activities of daily living (IADL) and the handgrip strength with oral self-care among dentate home-dwelling elderly people in Finland.

Materials And Methods: The study analysed data for 168 dentate participants (mean age 80.6 years) in the population-based Geriatric Multidisciplinary Strategy for Good Care of the Elderly (GeMS) study. Each participant received a clinical oral examination and structured interview in 2004-2005. Functional status was assessed using the IADL scale and handgrip strength was measured using handheld dynamometry.

Results: Study participants with high IADL (scores 7-8) had odds ratios (ORs) for brushing their teeth at least twice a day of 2.7 [95% confidence intervals (CI) 1.1-6.8], for using toothpaste at least twice a day of 2.0 (CI 0.8-5.2) and for having good oral hygiene of 2.8 (CI 1.0-8.3) when compared with participants with low IADL (scores ≤6). Participants in the upper tertiles of the handgrip strength had ORs for brushing the teeth at least twice a day of 0.9 (CI 0.4-1.9), for using the toothpaste at least twice a day of 0.9 (CI 0.4-1.8) and for good oral hygiene of 1.1 (CI 0.5-2.4) in comparison with the study subjects in the lowest tertile of handgrip strength.

Conclusion: The results of this study suggest that the functional status, measured by means of the IADL scale, but not handgrip strength, is an important determinant of oral self-care among the home-dwelling elderly.
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http://dx.doi.org/10.1111/j.1741-2358.2010.00427.xDOI Listing
June 2012

Sedative load among community-dwelling people aged 75 years and older: a population-based study.

Drugs Aging 2011 Nov;28(11):913-25

Kuopio Research Centre of Geriatric Care, Clinical Pharmacology and Geriatric Pharmacotherapy Unit, School of Pharmacy, Department of Geriatrics, Faculty of Health Sciences, University of Eastern Finland, and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.

Background: Drugs with sedative properties are among the most widely used drugs in community-dwelling older people. Use of sedative drugs has been associated with falls and fractures, cognitive and memory impairment and impaired physical function among older people. The sedative load model has been developed to quantify the cumulative effect of taking multiple drugs with sedative properties.

Objective: The objective of the study was to investigate factors associated with sedative load among community-dwelling older people, using data collected as part of the Finnish Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study.

Methods: The GeMS study was a randomized, comparative study that evaluated a model for geriatric assessment, care and rehabilitation using a study sample of 1000 persons aged≥75 years who were living in Kuopio, Finland. Of these, 700 people consented to participate and were community-dwelling. Demographic, diagnostic and drug use data (both regular and when-required drugs) were elicited during nurse interviews. For the current analysis, sedative load was computed using a previously published model, in which drugs taken on a regular and when-required basis were classified into one of four groups according to their sedative potential. Group 1 included primary sedatives (sedative rating 2) and group 2 included drugs with sedation as a prominent side effect (sedative rating 1). Each participant's sedative load was calculated by summing the sedative ratings of group 1 and 2 drugs. Logistic regression models were used to investigate factors associated with sedative load.

Results: Twenty-nine percent of participants (n=205) had a sedative load of ≥1 (i.e. used one or more drugs with sedative properties), and 22% (n=158) had a sedative load of ≥2 (i.e. used either one primary sedative or two drugs with sedation as a prominent adverse effect or preparations with a sedating component) when considering regularly used drugs. A sedative load of ≥2 that related to regularly used drugs was associated with female sex (odds ratio [OR] 1.65; 95% CI 1.02, 2.67), poor self-perceived health (OR 2.06; 95% CI 1.25, 3.38), impaired instrumental activities of daily living [IADL] (OR 1.89; 95% CI 1.18, 3.01) and often feeling lonely (OR 4.72; 95% CI 2.15, 10.40). The same factors remained significantly associated with a sedative load of ≥2 after drugs used on a when-required basis were included in the analyses.

Conclusions: The advantages of the sedative load model were that it included drugs with sedative properties prescribed for somatic diseases, described cumulative exposure to drugs that exert sedative effects through multiple mechanisms in the CNS, and incorporated a sedative rating for each drug. In an older population, female sex, impaired IADL, poor self-perceived health, and loneliness were associated with higher sedative load. Clinicians should remain cognizant of these factors when reviewing drug regimens and targeting interventions to optimize sedative use.
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http://dx.doi.org/10.2165/11597800-000000000-00000DOI Listing
November 2011

Effects of comprehensive geriatric assessment and targeted intervention on mobility in persons aged 75 years and over: a randomized controlled trial.

Clin Rehabil 2012 Apr 17;26(4):314-26. Epub 2011 Oct 17.

Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Finland.

Objective: To assess the effect of a comprehensive geriatric assessment and individually tailored intervention on mobility in older people. In addition, the effectiveness of the geriatric intervention was evaluated among a subgroup of persons with musculoskeletal pain.

Design: Three-year geriatric development project with randomized assignment to intervention and control group.

Setting: Research centre, community and assisted living facilities.

Participants: Seven hundred and eighty-one Finnish persons aged 75-98 years were assigned to an intervention (n = 404) or control (n = 377) group.

Intervention: A comprehensive geriatric assessment with a multifactorial intervention lasting two years. The intervention included individualized referrals, recommendations, physical activity counselling and supervised resistance training.

Measurements: Perceived limitation in walking 400m was gathered annually during the intervention and at the one-year post-intervention follow-up.

Results: The proportion of persons with mobility limitation at the beginning, at the two-year intervention and at the one-year post-intervention follow-up was 16%, 15%, 12% and 14%, respectively, in the intervention group. In the control group, the corresponding proportions were 19%, 18%, 23% and 26%. The treatment effect was significant at the end of the two-year intervention (odds ratio 0.82, 95% confidence interval 0.70-0.96, P = 0.013), and at the one-year post-intervention follow-up (0.84, 0.75-0.94, P = 0.002). The parallel positive effect of the intervention on mobility was even greater among persons with musculoskeletal pain.

Conclusion: The comprehensive geriatric assessment and individually tailored multifactorial intervention had a positive effect on mobility, underlining their importance in health promotion and disability prevention in older people.
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http://dx.doi.org/10.1177/0269215511423269DOI Listing
April 2012
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