Browsing by Subject "DEMENTIA"

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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.
  • Kuuluvainen, Liina; Pöyhönen, Minna; Pasanen, Petra; Siitonen, Maija; Rummukainen, Jaana; Tienari, Pentti J.; Paetau, Anders; Myllykangas, Liisa (2017)
    Mutations in the progranulin (GRN) gene represent about 5-10% of frontotemporal lobar degeneration (FTLD). We describe a proband with a novel GRN mutation c.687T>A, p.(Tyr229*), presenting with dyspraxia, dysgraphia, and dysphasia at the age of 60 and a very severe FTLD neuropathological phenotype with TDP43 inclusions. The nephew of the proband had signs of dementia and personality changes at the age of 60 and showed similar but milder FTLD pathology. Three other family members had had early-onset dementia. Gene expression studies showed decreased GRN gene expression in mutation carriers' blood samples. In conclusion, we describe a novel GRN, p.(Tyr229*) mutation, resulting in haploinsufficiency of GRN and a severe neuropathologic FTLD phenotype.
  • Yu, Nancy Y.; Bieder, Andrea; Raman, Amitha; Mileti, Enrichetta; Katayama, Shintaro; Einarsdottir, Elisabet; Fredholm, Bertil B.; Falk, Anna; Tapia-Paez, Isabel; Daub, Carsten O.; Kere, Juha (2017)
    Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 mu M and 10 mu M), over a period of 9 h. We found dosage-dependent activation of immediate early genes after 1 h. Neuronal projection development processes were up-regulated and negative regulation of axon extension processes were down-regulated at 3 h. In addition, genes involved in extracellular matrix organization, response for wound healing, and regulation of immune system processes were down-regulated by caffeine at 3 h. This study identified novel genes within the neuronal projection guidance pathways that respond to acute caffeine stimulation and suggests potential mechanisms for the effects of caffeine on neuronal cells.
  • Sauna-aho, Oili; BjelogrlicLaakso, Nina; Rautava, Päivi; Arvio, Maria (2020)
    Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The aim of our longitudinal study was to describe ageing-related cognitive changes in men with FXS. Method A neuropsychologist determined the raw scores (RSs) of 19 men with FXS twice with the Leiter International Performance Scale at an average interval of 22 years. The ages of the participants at baseline ranged from 16 to 50 (mean 27) years. Results At follow-up, the RSs improved in two men, remained the same in two men and declined in 15 men. Overall, the RS of the study group deteriorated by an average 4 points in RSs (p <.001). Conclusion Cognitive ageing in men with FXS started earlier than that in men in the general population; in many cases, cognitive ageing in men with FXS began before middle age, usually without any medical or other underlying cause.
  • Kok, Eloise H.; Savola, Sara; Raunio, Anna; Oinas, Minna; Tuimala, Jarno; Polvikoski, Tuomo; Kero, Mia; Kaivola, Karri; Tienari, Pentti J.; Paetau, Anders; Myllykangas, Liisa (2021)
  • Annanmaki, Tua; Palmu, Kirsi; Murros, Kari; Partanen, Juhani (2017)
    The diagnosis of cognitive impairment and dementia often occurring with Parkinson's disease (PD) is still based on the clinical picture and neuropsychological examination. Ancillary methods to detect cognitive decline in these patients are, therefore, needed. Alterations in the latencies and amplitudes of evoked response potential (ERP) components N100 and P200 have been described in PD. Due to limited number of studies their relation to cognitive deficits in PD remains obscure. The present study was designed to examine if alterations in the N100- and P200-potentials associate with neuropsychological impairment in PD. EEG-ERP was conducted to 18 PD patients and 24 healthy controls. The patients underwent a thorough neuropsychological evaluation. The controls were screened for cognitive impairment with Consortium to Establish Alzheimer's disease (CERAD)-testing and a normal result were required to be included in the study. The N100-latency was prolonged in the patients compared to the controls (p = 0.05). In the patients, the N100 latency correlated significantly with a visual working memory task (p = 0.01). Also N100 latency was prolonged and N100 amplitude habituation diminished in the patients achieving poorly in this task. We conclude that prolonged N100-latency and diminished amplitude habituation associate with visual working memory impairment in PD.
  • Weichert, I.; Romero-Ortuno, R.; Tolonen, J.; Soe, T.; Lebus, C.; Choudhury, S.; Nadarajah, C. V.; Nanayakkara, P.; Orru, M.; Di Somma, S. (2018)
    What is known and objectiveDrugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. MethodsThis is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. Results and discussion21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naive patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR=1.82, 95% CI for OR: 1.36-2.45, P What is new and conclusionThere was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.
  • Leskinen, Heidi; Tringham, Maaria; Karjalainen, H.; Iso-Touru, T.; Hietaranta-Luoma, Hanna-Leena; Marnila, P.; Pihlava, J.-M.; Hurme, T.; Puolijoki, H.; Åkerman, K.; Mäkinen, Sari; Sandell, Mari; Vähäkangas, K.; Tahvonen, R.; Rokka, Susanna; Hopia, Anu (2022)
    Introduction: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer’s disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common. Methods: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire. Results: APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele. Conclusions: The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.
  • Janssen, Niels; Handels, Ron L.; Wimo, Anders; Antikainen, Riitta; Laatikainen, Tiina; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia; Evers, Silvia M. A. A.; Verhey, Frans R. J.; Ngandu, Tiia (2022)
    Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n= 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.
  • 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.
  • Salminen, K. S.; Suominen, M. H.; Soini, H.; Kautiainen, H.; Savikko, N.; Saarela, R. K. T.; Muurinen, S.; Pitkälä, K. H. (2019)
    ObjectivesWe evaluated the associations between nutritional status and health-related quality-of-life (HRQoL) among older long-term care residents in Helsinki.Design and participantsAll 3767 older (65 years) long-term care residents in Helsinki in 2017 were invited to participate in this cross-sectional study. After refusals and exclusions of residents without sufficient information, 2160 residents remained.MeasurementsData on characteristics, nutritional status (Mini Nutritional Assessment, MNA) and HRQoL (15D) were collected by trained nurses.ResultsOf the participants, 64% were at-risk of malnutrition and 18% suffered from malnutrition. Residents in the malnourished group were more dependent in activities of daily living (ADL) functioning, suffered more often from dementia, had lower cognitive level, used less medications, and were eating more often inadequately. HRQoL was statistically significantly associated with MNA total score in both female and male residents. There was a curvilinear correlation between MNA and 15D score in females: 0.50 (95% CI 0.46 to 0.53) and males: 0.56 (95% CI 0.50 to 0.61). In partial correlation analysis, all dimensions of 15D, except for sleeping and breathing, were positively associated with MNA score. In these analyses no significant differences emerged between males and females when the results were adjusted for age and dementia.ConclusionsNutrition plays an important role in HRQoL among older long-term care residents.
  • Lampinen, Riikka; Gorova, Veronika; Avesani, Simone; Liddell, Jeffrey R.; Penttilä, Elina; Zavodna, Tana; Krejcik, Zdenek; Lehtola, Juha-Matti; Saari, Toni; Kalapudas, Juho; Hannonen, Sanna; Lopponen, Heikki; Topinka, Jan; Koivisto, Anne M.; White, Anthony R.; Giugno, Rosalba; Kanninen, Katja M. (2022)
    Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.
  • Kaivola, Karri; Kiviharju, Anna; Jansson, Lilja; Rantalainen, Ville; Eriksson, Johan G.; Strandberg, Timo E.; Laaksovirta, Hannu; Renton, Alan E; Traynor, Bryan J.; Myllykangas, Liisa; Tienari, Pentti (2019)
    The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.
  • Hakala, JO; Pahkala, K; Juonala, M; Salo, P; Kahonen, M; Hutri-Kahonen, N; Lehtimaki, T; Laitinen, TP; Jokinen, E; Taittonen, L; Tossavainen, P; Viikari, JSA; Raitakari, OT; Rovio, SP (2021)
    Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (beta=-0.262 SD [95% CI, -0.520 to -0.005]) and serum total cholesterol (beta=-0.214 SD [95% CI, -0.365 to -0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (beta=-0.407 SD [95% CI, -0.708 to -0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning (P for trend=0.008; 3 cardiovascular risk factors: beta=-0.390 SD [95% CI, -0.691 to -0.088]), with visual processing and sustained attention (P for trend Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.
  • Rovio, Suvi P.; Pahkala, Katja; Nevalainen, Jaakko; Juonala, Markus; Salo, Pia; Kahonen, Mika; Hutri-Kahonen, Nina; Lehtimaki, Terho; Jokinen, Eero; Laitinen, Tomi; Taittonen, Leena; Tossavainen, Paivi; Viikari, Jorma S. A.; Rinne, Juha O.; Raitakari, Olli T. (2017)
    BACKGROUND In adults, high blood pressure (BP), adverse serum lipids, and smoking associate with cognitive deficits. The effects of these risk factors from childhood on midlife cognitive performance are unknown. OBJECTIVES This study sought to investigate the associations between childhood/adolescence cardiovascular risk factors and midlife cognitive performance. METHODS From 1980, a population-based cohort of 3,596 children (baseline age: 3 to 18 years) have been followed for 31 years in 3- to 9-year intervals. BP, serum lipids, body mass index, and smoking were assessed in all follow-ups. Cumulative exposure as the area under the curve for each risk factor was determined in childhood (6 to 12 years), adolescence (12 to 18 years), and young adulthood (18 to 24 years). In 2011, cognitive testing was performed in 2,026 participants aged 34 to 49 years. RESULTS High systolic BP, elevated serum total-cholesterol, and smoking from childhood were independently associated with worse midlife cognitive performance, especially memory and learning. The number of early life risk factors, including high levels (extreme 75th percentile for cumulative risk exposure between ages 6 and 24 years) of systolic BP, total-cholesterol, and smoking associated inversely with midlife visual and episodic memory and visuospatial associative learning (-0.140 standard deviations per risk factor, p <0.0001) and remained significant after adjustment for contemporaneous risk factors. Individuals with all risk factors within recommended levels between ages 6 and 24 years performed 0.29 standard deviations better (p = 0.006) on this cognitive domain than those exceeding all risk factor guidelines at least twice. This difference corresponds to the effect of 6 years aging on this cognitive domain. CONCLUSIONS Cumulative burden of cardiovascular risk factors from childhood/adolescence associate with worse midlife cognitive performance independent of adulthood exposure. (C) 2017 by the American College of Cardiology Foundation.
  • Jokanovic, Natali; Kautiainen, Hannu; Bell, J. Simon; Tan, Edwin C. K.; Pitkälä, Kaisu H. (2019)
    BackgroundOne quarter of residents in long-term care facilities (LTCFs) have a diagnosis of CHD or stroke and over half use at least one preventative cardiovascular medication. There have been no studies that have investigated the longitudinal change in secondary preventative cardiovascular medication use in residents in LTCFs over time.ObjectiveThe aim of this study was to investigate the change in cardiovascular medication use among residents with coronary heart disease (CHD) and prior stroke in nursing homes (NHs) and assisted living facilities (ALFs) in Finland over time, and whether this change differs according to dementia status.MethodsThree comparable cross-sectional audits of cardiovascular medication use among residents aged 65years and over with CHD or prior stroke in NHs in 2003 and 2011 and ALFs in 2007 and 2011 were compared. Logistic regression analyses adjusted for gender, age, mobility, cancer and length of stay were performed to examine the effect of study year, dementia and their interaction on medication use.ResultsCardiovascular medication use among residents with CHD (NHs: 89% vs 70%; ALFs: 89% vs 84%) and antithrombotic medication use among residents with stroke (NHs: 72% vs 63%; ALFs: 78% vs 69%) declined between 2003 and 2011 in NHs and 2007 and 2011 in ALFs.Decline in the use of diuretics, nitrates and digoxin were found in both groups and settings. Cardiovascular medication use among residents with CHD and dementia declined in NHs (88% [95% CI 85-91] in 2003 vs 70% [95% CI 64-75] in 2011) whereas there was no change among people without dementia. There was no change in cardiovascular medication use among residents with CHD in ALFs with or without dementia over time. Antithrombotic use was lower in residents with dementia compared with residents without dementia in NHs (p
  • Pitkala, Kaisu H.; Strandberg, Timo E. (2022)
    Randomised controlled trials (RCTs) usually provide the best evidence for treatments and management. Historically, older people have often been excluded from clinical medication trials due to age, multimorbidity and disabilities. The situation is improving, but still the external validity of many trials may be questioned. Individuals participating in trials are generally less complex than many patients seen in geriatric clinics. Recruitment and retention of older participants are particular challenges in clinical trials. Multiple channels are needed for successful recruitment, and especially individuals experiencing frailty, multimorbidity and disabilities require support to participate. Cognitive decline is common, and often proxies are needed to sign informed consent forms. Older people may fall ill or become tired during the trial, and therefore, special support and empathic study personnel are necessary for the successful retention of participants. Besides the risk of participants dropping out, several other pitfalls may result in underestimating or overestimating the intervention effects. In nonpharmacological trials, imperfect blinding is often unavoidable. Interventions must be designed intensively and be long enough to reveal differences between the intervention and control groups, as control participants must still receive the best normal care available. Outcome measures should be relevant to older people, sensitive to change and targeted to the specific population in the trial. Missing values in measurements are common and should be accounted for when designing the trial. Despite the obstacles, RCTs in geriatrics must be promoted. Reliable evidence is needed for the successful treatment, management and care of older people.
  • Hale, Jo Mhairi; Schneider, Daniel C.; Mehta, Neil K.; Myrskylä, Mikko (2020)
    Prior studies have analyzed the burden of cognitive impairment, but often use potentially biased prevalence-based methods or measure only years lived with impairment, without estimating other relevant metrics. We use the Health and Retirement Study (1998–2014; n = 29,304) and the preferred incidence-based Markov-chain models to assess three key measures of the burden of cognitive impairment: lifetime risk, mean age at onset, and number of years lived impaired. We analyze both mild and severe cognitive impairment (dementia) and gender, racial/ethnic, and educational variation in impairment. Our results paint a multi-dimensional picture of cognitive health, presenting the first comprehensive analysis of the burden of cognitive impairment for the U.S. population age 50 and older. Approximately two out of three Americans experience some level of cognitive impairment at an average age of approximately 70 years. For dementia, lifetime risk for women (men) is 37% (24%) and mean age at onset 83 (79) years. Women can expect to live 4.2 years with mild impairment and 3.2 with dementia, men 3.5 and 1.8 years. A critical finding is that for the most advantaged groups (i.e., White and/or higher educated), cognitive impairment is both delayed and compressed toward the very end of life. In contrast, despite the shorter lives of disadvantaged subgroups (Black and/or lower educated), they experience a younger age of onset, higher lifetime risk, and more years cognitively impaired. For example, men with at least an Associate degree have 21% lifetime dementia risk, compared to 35% among men with less than high school education. White women have 6 years of cognitively-impaired life expectancy, compared to 12 and 13 years among Black women and Latinas. These educational and racial/ethnic gradients highlight the very uneven burden of cognitive impairment. Further research is required to identify the mechanisms driving these disparities in cognitive impairment.
  • Alenius, Minna; Koskinen, Sanna; Hallikainen, Ilona; Ngandu, Tiia; Lipsanen, Jari; Sainio, Päivi; Tuulio-Henriksson, Annamari; Hänninen, Tuomo (2019)
    Background/Aims: To detect cognitive decline in older adults, measures of verbal fluency and verbal memory are widely used. Less is known about performance in these measures in younger persons or according to education level and gender. We investigated cognitive performance according to age, education and gender among cognitively healthy adults aged 30-100 years. Methods: The study population comprised 4,174 cognitively healthy persons participating in the nationally representative Finnish Health 2011 survey. Cognitive assessment included verbal fluency, word list memory, word list recall and word list savings from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: Total variance in the cognitive test performance explained by age, education and gender varied from 12.3 to 31.2%. A decreasing trend in cognitive performance existed in all subtests by advancing age, with differences appearing between 50 and 55 years. Persons with the highest-education level performed best for all measures. For the participants <55 years, education explained part of the variance, while age and gender did not. Conclusions: When assessing cognition, age and education should be accounted for in more detail in research and clinical practice. Additionally, the cohort effect and its potential impact on the renewal cycle of future normative values for cognitive tests should be considered. (C) 2019 The Author(s) Published by S. Karger AG, Basel
  • Alenius, Minna; Hokkanen, Laura; Koskinen, Sanna; Hallikainen, Ilona; Hänninen, Tuomo; Karrasch, Mira; Raivio, Minna M.; Laakkonen, Marja-Liisa; Krüger, Johanna; Suhonen, Noora-Maria; Kivipelto, Miia; Ngandu, Tiia (2022)
    We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer's disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010-2013 (aged 60-81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.