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154. The effect of stimulation therapy and donepezil on cognitive function in Alzheimer’s disease. A community based RCT with a two-by-two factorial design

Author

Andersen Fred, Viitanen Matti, Halvorsen Dag S, Straume Bjørn, Wilsgaard Tom, and Engstad Torgeir A

Subjects
Alzheimer’s disease, Symptomatic treatment, Postponement of cognitive deterioration, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Progressive neurodegeneration in Alzheimer’s disease (AD) induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD. Method Design: A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added. Setting: Nine rural municipalities in Northern Norway. Participants: 187 participants 65 years and older with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. INTERVENTIONS: In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blindly to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period. Main outcome: Changes in MMSE sum score. Secondary outcome: Changes in ADAS-Cog and Clock Drawing Test. Results MMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo. Conclusion In rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results. Trial registration ClinicalTrials.gov (Identifier: NCT00443014). EudraCT database (no 2004-002613-37).

Published
2012
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155. NF‐E2‐related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin‐1 mutated Alzheimer's disease astrocytes

Author

Oksanen, Minna, primary, Hyötyläinen, Ida, additional, Trontti, Kalevi, additional, Rolova, Taisia, additional, Wojciechowski, Sara, additional, Koskuvi, Marja, additional, Viitanen, Matti, additional, Levonen, Anna‐Liisa, additional, Hovatta, Iiris, additional, Roybon, Laurent, additional, Lehtonen, Šárka, additional, Kanninen, Katja M., additional, Hämäläinen, Riikka H., additional, and Koistinaho, Jari, additional

Published
2019
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156. Midlife Insulin Resistance as a Predictor for Late-Life Cognitive Function and Cerebrovascular Lesions

Author

Toppala, Sini, primary, Ekblad, Laura L., additional, Lötjönen, Jyrki, additional, Helin, Semi, additional, Hurme, Saija, additional, Johansson, Jarkko, additional, Jula, Antti, additional, Karrasch, Mira, additional, Koikkalainen, Juha, additional, Laine, Hanna, additional, Parkkola, Riitta, additional, Viitanen, Matti, additional, and Rinne, Juha O., additional

Published
2019
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159. Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the Dementia Study in Northern Norway

Author

Halvorsen Dag S, Straume Bjørn, Viitanen Matti, Andersen Fred, and Engstad Torgeir A

Subjects
Geriatrics, RC952-954.6
Abstract

Abstract Background Inappropriate medical treatment of co-morbidities in Alzheimer's disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. Methods Setting: Nine rural municipalities with 70 000 inhabitants in Northern Norway. Participants: Participants with and without AD recruited in general practice and by population based screening. 187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression. Results A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1 ± 3.6 and 2.9 ± 2.4 respectively, p < 0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9 ± 3.9 and 4.5 ± 3.3, respectively, p < 0.001). Conclusions AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors.

Published
2011
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162. Recruitment methods in Alzheimer's disease research: general practice versus population based screening by mail

Author

Halvorsen Dag S, Viitanen Matti, Straume Bjørn, Engstad Torgeir A, Andersen Fred, Hykkerud Samuel, and Sjøbrend Kjell

Subjects
Medicine (General), R5-920
Abstract

Abstract Background In Alzheimer's disease (AD) research patients are usually recruited from clinical practice, memory clinics or nursing homes. Lack of standardised inclusion and diagnostic criteria is a major concern in current AD studies. The aim of the study was to explore whether patient characteristics differ between study samples recruited from general practice and from a population based screening by mail within the same geographic areas in rural Northern Norway. Methods An interventional study in nine municipalities with 70000 inhabitants was designed. Patients were recruited from general practice or by population based screening of cognitive function by mail. We sent a questionnaire to 11807 individuals ≥ 65 years of age of whom 3767 responded. Among these, 438 individuals whose answers raised a suspicion of cognitive impairment were invited to an extended cognitive and clinical examination. Descriptive statistics, chi-square, independent sample t-test and analyses of covariance adjusted for possible confounders were used. Results The final study samples included 100 patients recruited by screening and 87 from general practice. Screening through mail recruited younger and more self-reliant male patients with a higher MMSE sum score, whereas older women with more severe cognitive impairment were recruited from general practice. Adjustment for age did not alter the statistically significant differences of cognitive function, self-reliance and gender distribution between patients recruited by screening and from general practice. Conclusions Different recruitment procedures of individuals with cognitive impairment provided study samples with different demographic characteristics. Initial cognitive screening by mail, preceding extended cognitive testing and clinical examination may be a suitable recruitment strategy in studies of early stage AD. Clinical Registration ClinicalTrial.gov Identifier: NCT00443014

Published
2010
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176. Caring for a Person With Dementia on the Margins of Long-Term Care: A Perspective on Burden From 8 European Countries

Author

Sutcliffe, Caroline, Giebel, Clarissa, Bleijlevens, Michel, Lethin, Connie, Stolt, Minna, Saks, Kai, Soto, Maria E., Meyer, Gabriele, Zabalegui, Adelaida, Chester, Helen, Challis, David, Stephan, Astrid, Renom-Guiteras, Anna, Sauerland, Dirk, Bremer, Patrick, Hamers, Jan P.H., Afram, Basema, Beerens, Hanneke C., Verbeek, Hilde, Zwakhalen, Sandra M.G., Ruwaard, Dirk, Ambergen, Ton, Hallberg, Ingalill Rahm, Emilsson, Ulla Melin, Karlsson, Staffan, Jolley, David, Tucker, Sue, Bowns, Ian, Roe, Brenda, Burns, Alistair, Leino-Kilpi, Helena, Koskenniemi, Jaana, Suhonen, Riitta, Viitanen, Matti, Arve, Seija, Hupli, Maija, Tiit, Ene Margit, Leibur, Jelena, Raamat, Katrin, Armolik, Angelika, Toivari, Teija Tuula Marjatta, Navarro, Montserrat, Cabrera, Esther, Risco, Ester, Alvira, Carme, Farre, Marta, Miguel, Susana, Milhet, Agathe, Sourdet, Sandrine, Gillette, Sophie, and Vellas, Bruno

Subjects
human activities, humanities
Abstract

© 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine Objectives To explore associations between carer burden and characteristics of (1) the informal carer, (2) the person with dementia, and (3) the care support network in 8 European countries. Design Cross-sectional study. Setting People with dementia judged at risk of admission to long-term care (LTC) facilities in 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, United Kingdom). Participants A total of 1223 people with dementia supported by community services at home or receiving day care or respite care and their informal carers. Measurements Variables regarding the informal carer included familial relationship and living situation. Variables relating to the person with dementia included cognitive functioning (S-MMSE), neuropsychiatric symptoms (NPI-Q), depressive symptoms (Cornell depression scale), comorbidity (Charlson Comorbidity Index), and physical functioning (Katz Activity of Daily Living [ADL] Index). The care support network was measured using hours of caregiving (ADLs, instrumental ADLs [IADLs], supervision), additional informal care support, and service receipt (home care, day care). Experience of carer burden was recorded using the Zarit Burden Interview. Logistic regression analysis was used to determine factors associated with high carer burden. Results Carer burden was highest in Estonia (mean 39.7/88) and lowest in the Netherlands (mean 26.5/88). High burden was significantly associated with characteristics of the informal carer (family relationship, specifically wives or daughters), of the person with dementia (physical dependency in ADLs; neuropsychiatric symptoms, in particular nighttime behaviors and irritability), the care support network (hours of caregiving supervision; receipt of other informal care support) and country of residence. Conclusion A range of factors are associated with burden in informal carers of people with dementia judged to be on the margins of LTC. Support for informal carers needs to take account of gender differences. The dual challenges of distressed behaviors and difficulties in ADLs by the person with dementia may be addressed by specific nonpharmacological interventions focusing on both elements. The potential protective effect of additional informal support to carers highlights the importance of peer support or better targeted home support services. The implementation of appropriate and tailored interventions to reduce burden by supporting informal carers may enable people with dementia to remain at home for longer.

Published
2017

179. NF‐E2‐related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin‐1 mutated Alzheimer's disease astrocytes.

Author

Oksanen, Minna, Hyötyläinen, Ida, Trontti, Kalevi, Rolova, Taisia, Wojciechowski, Sara, Koskuvi, Marja, Viitanen, Matti, Levonen, Anna‐Liisa, Hovatta, Iiris, Roybon, Laurent, Lehtonen, Šárka, Kanninen, Katja M., Hämäläinen, Riikka H., and Koistinaho, Jari

Published
2020
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183. Effect of homogenised and pasteurised versus native cows' milk on gastrointestinal symptoms, intestinal pressure and postprandial lipid metabolism

Author

Nuora, Anu, primary, Tupasela, Tuomo, additional, Tahvonen, Raija, additional, Rokka, Susanna, additional, Marnila, Pertti, additional, Viitanen, Matti, additional, Mäkelä, Petri, additional, Pohjankukka, Jonne, additional, Pahikkala, Tapio, additional, Yang, Baoru, additional, Kallio, Heikki, additional, and Linderborg, Kaisa, additional

Published
2018
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184. Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGF β expression

Author

Panahi, Mahmod, primary, Yousefi Mesri, Naeimeh, additional, Samuelsson, Eva‐Britt, additional, Coupland, Kirsten G., additional, Forsell, Charlotte, additional, Graff, Caroline, additional, Tikka, Saara, additional, Winblad, Bengt, additional, Viitanen, Matti, additional, Karlström, Helena, additional, Sundström, Erik, additional, and Behbahani, Homira, additional

Published
2018
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185. Costs of Care of Agitation Associated With Dementia in 8 European Countries: Results From the RightTimePlaceCare Study

Author

Costa, Nadège, primary, Wübker, Ansgar, additional, De Mauléon, Adelaïde, additional, Zwakhalen, Sandra M.G., additional, Challis, David, additional, Leino-Kilpi, Helena, additional, Hallberg, Ingalill R., additional, Stephan, Astrid, additional, Zabalegui, Adelaida, additional, Saks, Kai, additional, Molinier, Laurent, additional, Wimo, Anders, additional, Vellas, Bruno, additional, Sauerland, Dirk, additional, Binot, Ingrid, additional, Soto, Maria E., additional, Meyer, Gabriele, additional, Renom Guiteras, Anna, additional, Bremer, Patrick, additional, Hamers, Jan P.H., additional, Afram, Basema, additional, Beerens, Hanneke C., additional, Bleijlevens, Michel H.C., additional, Verbeek, Hilde, additional, Ruwaard, Dirk, additional, Rahm Hallberg, Ingalill, additional, Emilsson, Ulla Melin, additional, Karlsson, Staffan, additional, Sutcliffe, Caroline, additional, Jolley, David, additional, Tucker, Sue, additional, Bowns, Ian, additional, Roe, Brenda, additional, Burns, Alistair, additional, Koskenniemi, Jaana, additional, Suhonen, Riitta, additional, Viitanen, Matti, additional, Arve, Seija, additional, Stolt, Minna, additional, Hupli, Maija, additional, Tiit, Ene-Margit, additional, Leibur, Jelena, additional, Raamat, Katrin, additional, Armolik, Angelika, additional, Marjatta Toivari, Teija Tuula, additional, Navarro, Montserrat, additional, Cabrera, Esther, additional, Risco, Ester, additional, Soto, Maria, additional, Milhet, Agathe, additional, Sourdet, Sandrine, additional, and Gillette, Sophie, additional

Published
2018
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186. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease

Author

Almkvist, Ove, Rodriguez-Vieitez, Elena, Thordardottir, Steinunn, Amberla, Kaarina, Axelman, Karin, Basun, Hans, Kinhult-Stahlbom, Anne, Lilius, Lena, Remes, Anne, Wahlund, Lars-Olof, Viitanen, Matti, Lannfelt, Lars, Graff, Caroline, Almkvist, Ove, Rodriguez-Vieitez, Elena, Thordardottir, Steinunn, Amberla, Kaarina, Axelman, Karin, Basun, Hans, Kinhult-Stahlbom, Anne, Lilius, Lena, Remes, Anne, Wahlund, Lars-Olof, Viitanen, Matti, Lannfelt, Lars, and Graff, Caroline

Abstract

Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.

Published
2017
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187. Oral Glucose Tolerance Test Predicts Episodic Memory Decline: A 10-Year Population-Based Follow-up Study.

Author

Toppala, Sini, Ekblad, Laura L., Viitanen, Matti, Rinne, Juha O., and Jula, Antti

Abstract

Objective: To examine if the 2-h value of an oral glucose tolerance test (OGTT) can predict cognitive decline.Research Design and Methods: This study is based on a subpopulation of the Finnish population-based Health 2000 Survey and its follow-up, the Health 2011 study. Altogether, 961 individuals aged 45-74 (mean 55.6 years; 55.8% women) underwent OGTT in 2001-2002. Categorical verbal fluency, word-list learning, and word-list delayed recall were tested at baseline and at follow-up in 2011. Statistical analyses were performed with multivariable linear models adjusted for previously reported risk factors for cognitive decline.Results: A higher 2-h glucose value in the OGTT at baseline predicted worse performance (slope: -0.08; P = 0.01) and greater decline (slope: -0.07; P = 0.007) in the word-list delayed recall test after 10 years.Conclusions: Our results indicate that higher 2-h glucose values in the OGTT predict a decline in episodic memory after 10 years. [ABSTRACT FROM AUTHOR]

Published
2021
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189. Frailty, walking ability and self-rated health in predicting institutionalization: an 18-year follow-up study among Finnish community-dwelling older people

Author

Viljanen, Anna, Salminen, Marika, Irjala, Kerttu, Korhonen, Päivi, Wuorela, Maarit, Isoaho, Raimo, Kivelä, Sirkka-Liisa, Vahlberg, Tero, Viitanen, Matti, Löppönen, Minna, and Viikari, Laura

Abstract

Background: In clinical practice, there is a need for an instrument to screen older people at risk of institutionalization. Aims: To analyze the association of frailty, walking-ability and self-rated health (SRH) with institutionalization in Finnish community-dwelling older people. Methods: In this prospective study with 10- and 18-year follow-ups, frailty was assessed using FRAIL Scale (FS) (n= 1087), Frailty Index (FI) (n= 1061) and PRISMA-7 (n= 1055). Walking ability was assessed as self-reported ability to walk 400 m (n= 1101). SRH was assessed by a question of general SRH (n= 1105). Cox regression model was used to analyze the association of the explanatory variables with institutionalization. Results: The mean age of the participants was 73.0 (range 64.0‒97.0) years. Prevalence of institutionalization was 40.8%. In unadjusted models, frailty was associated with a higher risk of institutionalization by FS in 10-year follow-up, and FI in both follow-ups. Associations by FI persisted after age- and gender-adjustments in both follow-ups. By PRISMA-7, frailty predicted a higher risk of institutionalization in both follow-ups. In unadjusted models, inability to walk 400 m predicted a higher risk of institutionalization in both follow-ups and after adjustments in 10-year follow-up. Poor SRH predicted a higher risk of institutionalization in unadjusted models in both follow-ups and after adjustments in 10-year follow-up. Discussion: Simple self-reported items of walking ability and SRH seemed to be comparable with frailty indexes in predicting institutionalization among community-dwelling older people in 10-year follow-up. Conclusions: In clinical practice, self-reported walking ability and SRH could be used to screen those at risk.

Published
2021
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192. PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease

Author

Oksanen, Minna, primary, Petersen, Andrew J., additional, Naumenko, Nikolay, additional, Puttonen, Katja, additional, Lehtonen, Šárka, additional, Gubert Olivé, Max, additional, Shakirzyanova, Anastasia, additional, Leskelä, Stina, additional, Sarajärvi, Timo, additional, Viitanen, Matti, additional, Rinne, Juha O., additional, Hiltunen, Mikko, additional, Haapasalo, Annakaisa, additional, Giniatullin, Rashid, additional, Tavi, Pasi, additional, Zhang, Su-Chun, additional, Kanninen, Katja M., additional, Hämäläinen, Riikka H., additional, and Koistinaho, Jari, additional

Published
2017
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195. [P3-101]: MULTI-INFARCT DEMENTIA OF SWEDISH TYPE IS CAUSED BY 3’UTR COL4A1 MUTATION

Author

Siitonen, M., primary, Hanson, A. Börjesson, additional, Pasanen, P., additional, Bras, Jose T., additional, Kern, S., additional, Kern, J., additional, Andersen, O., additional, Stanescu, H., additional, Kleta, R., additional, Baumann, M., additional, Kalaria, Raj N., additional, Kalimo, H., additional, Singleton, Andrew, additional, Hardy, John, additional, Myllykangas, Liisa, additional, Viitanen, Matti, additional, and Guerreiro, Rita, additional

Published
2017
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197. [P3-170]: HUMAN IPSC-DERIVED ALZHEIMER's DISEASE ASTROCYTES RECAPITULATE DISEASE-RELATED PHENOTYPES

Author

Oksanen, Minna, primary, Petersen, Andrew J., additional, Puttonen, Katja, additional, Hämäläinen, Riikka H., additional, Lehtonen, Šárka, additional, Leskelä, Stina, additional, Shakirzyanova, Anastasia, additional, Naumenko, Nikolay, additional, Viitanen, Matti, additional, Rinne, Juha O., additional, Kanninen, Katja, additional, Haapasalo, Annakaisa, additional, Tavi, Pasi, additional, Zhang, Su-Chun, additional, and Koistinaho, Jari, additional

Published
2017
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199. Multi-infarct dementia of Swedish type is caused by a 3’UTR mutation of COL4A1

Author

Siitonen, Maija, primary, Börjesson-Hanson, Anne, additional, Pöyhönen, Minna, additional, Ora, Ari, additional, Pasanen, Petra, additional, Bras, Jose, additional, Kern, Silke, additional, Kern, Jürgen, additional, Andersen, Oluf, additional, Stanescu, Horia, additional, Kleta, Robert, additional, Baumann, Marc, additional, Kalaria, Rajesh, additional, Kalimo, Hannu, additional, Singleton, Andy, additional, Hardy, John, additional, Viitanen, Matti, additional, Myllykangas, Liisa, additional, and Guerreiro, Rita, additional

Published
2017
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