%0 Journal Article %J J Alzheimers Dis %D 2023 %T Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population. %A Larsson, LE %A Wang, Rui %A Cederholm, Tommy %A Wiggenraad, Fleur %A Rydén, Marie %A Hagman, Göran %A Hellénius, Mai-Lis %A Kivipelto, Miia %A Thunborg, Charlotta %X

BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities.

OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients.

METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied.

RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92).

CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

%B J Alzheimers Dis %V 96 %P 777-788 %8 2023 Nov 07 %G eng %N 2 %R 10.3233/JAD-221186 %0 Journal Article %J J Alzheimers Dis %D 2020 %T Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia. %A Pekkala, Timo %A Hall, Anette %A Mangialasche, Francesca %A Kemppainen, Nina %A Mecocci, Patrizia %A Ngandu, Tiia %A Rinne, Juha O %A Soininen, Hilkka %A Tuomilehto, Jaakko %A Kivipelto, Miia %A Solomon, Alina %X

We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOEɛ4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.

%B J Alzheimers Dis %V 76 %P 1243-1248 %8 2020 Aug 18 %G eng %N 4 %R 10.3233/JAD-200145 %0 Journal Article %J J Alzheimers Dis %D 2019 %T Self and Informant Memory Reports in FINGER: Associations with Two-Year Cognitive Change. %A Vaskivuo, Laura %A Hokkanen, Laura %A Hänninen, Tuomo %A Antikainen, Riitta %A Bäckman, Lars %A Laatikainen, Tiina %A Paajanen, Teemu %A Stigsdotter-Neely, Anna %A Strandberg, Timo %A Tuomilehto, Jaakko %A Soininen, Hilkka %A Kivipelto, Miia %A Ngandu, Tiia %X

BACKGROUND: Subjective memory complaints (SMCs) may be the first sign of cognitive decline in aging.

OBJECTIVE: To examine whether SMCs reported by oneself and informant predict cognitive change over 2 years among at-risk elderly people, and to determine the relationship of different types of SMCs (prospective and retrospective memory complaints) and change in cognitive function.

METHODS: This investigation is part of the FINGER project, which is a multicenter randomized controlled trial aiming at preventing cognitive decline in cognitively healthy older adults with increased risk of dementia. A subsample of 303 control-group participants (aged 60-80 years) and their informants (n = 261) rated the frequency of SMCs, using the Prospective and Retrospective Memory Questionnaire (PRMQ). Cognitive performance was measured at baseline and at 1- and 2-year follow-up visits using a neuropsychological test battery.

RESULTS: Participants who reported more SMCs improved less in global cognition, executive function, and memory during the subsequent 2 years in the fully-adjusted analyses. Self-reported retrospective memory problems predicted less improvement in all cognitive domains, whereas prospective memory problems did not. Informant-reported memory problems were not linked to subsequent change in cognition.

CONCLUSION: Our results indicate that self-reported SMCs, measured with PRMQ, predict future cognitive change in several cognitive domains. By contrast, reports by informants were not linked to changes in cognition. Among cognitively healthy at-risk elderly individuals, the persons themselves observe more easily problems relevant for their future cognitive trajectories than their informants.

%B J Alzheimers Dis %V 71 %P 785-795 %8 2019 Oct 1 %G eng %N 3 %R 10.3233/JAD-190133 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Combining Cognitive, Genetic, and Structural Neuroimaging Markers to Identify Individuals with Increased Dementia Risk. %A Payton, Nicola M %A Kalpouzos, Grégoria %A Rizzuto, Debora %A Fratiglioni, Laura %A Kivipelto, Miia %A Bäckman, Lars %A Laukka, Erika J %X

BACKGROUND: Cognitive and biological markers have shown varying degrees of success in identifying persons who will develop dementia.

OBJECTIVE: To evaluate different combinations of cognitive and biological markers and identify prediction models with the highest accuracy for identifying persons with increased dementia risk.

METHODS: Neuropsychological assessment, genetic testing (apolipoprotein E -APOE), and structural magnetic resonance imaging (MRI) were performed for 418 older individuals without dementia (60-97 years) from a population-based study (SNAC-K). Participants were followed for six years.

RESULTS: Cognitive, genetic, and MRI markers were systematically combined to create prediction models for dementia at six years. The most predictive individual markers were perceptual speed or carrying at least one APOEɛ4 allele (AUC = 0.875). The most predictive model (AUC = 0.924) included variables from all three modalities (category fluency, general knowledge, any ɛ4 allele, hippocampal volume, white matter-hyperintensity volume).

CONCLUSION: This study shows that combining markers within and between modalities leads to increased predictivity for future dementia. However, minor increases in predictive value should be weighed against the cost of additional tests in larger-scale screening.

%B J Alzheimers Dis %V 64 %P 533-542 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29889068?dopt=Abstract %R 10.3233/JAD-180199 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults: The HATICE Trial. %A Barbera, Mariagnese %A Mangialasche, Francesca %A Jongstra, Susan %A Guillemont, Juliette %A Ngandu, Tiia %A Beishuizen, Cathrien %A Coley, Nicola %A Brayne, Carol %A Andrieu, Sandrine %A Richard, Edo %A Soininen, Hilkka %A Kivipelto, Miia %K Aged %K Aged, 80 and over %K Cardiovascular Diseases %K Cognitive Dysfunction %K Counseling %K Europe %K Exercise %K Female %K Healthy Aging %K Humans %K Internet %K Life Style %K Male %K Practice Guidelines as Topic %K Risk Factors %K Telemedicine %X

BACKGROUND: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults.

OBJECTIVE: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries.

METHODS: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention.

RESULTS: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country.

CONCLUSION: Despite differences in CVR management within the countries considered, it was possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.

%B J Alzheimers Dis %V 62 %P 649-663 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29480185?dopt=Abstract %R 10.3233/JAD-170858 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition. %A Stephen, Ruth %A Liu, Yawu %A Ngandu, Tiia %A Rinne, Juha O %A Kemppainen, Nina %A Parkkola, Riitta %A Laatikainen, Tiina %A Paajanen, Teemu %A Hänninen, Tuomo %A Strandberg, Timo %A Antikainen, Riitta %A Tuomilehto, Jaakko %A Keinänen Kiukaanniemi, Sirkka %A Vanninen, Ritva %A Helisalmi, Seppo %A Levälahti, Esko %A Kivipelto, Miia %A Soininen, Hilkka %A Solomon, Alina %X

BACKGROUND: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile.

OBJECTIVES: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures.

METHODS: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation.

RESULTS: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (β-coefficient -0.29, p = 0.001) and hippocampal volume (β-coefficient -0.28, p = 0.003), lower cortical thickness (β-coefficient -0.19, p = 0.042), and poorer cognition (β-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p < 0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15, 95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation.

CONCLUSIONS: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.

%B J Alzheimers Dis %V 59 %P 695-705 %G eng %N 2 %R 10.3233/JAD-170092 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Baseline Telomere Length and Effects of a Multidomain Lifestyle Intervention on Cognition: The FINGER Randomized Controlled Trial. %A Sindi, Shireen %A Ngandu, Tiia %A Hovatta, Iiris %A Kåreholt, Ingemar %A Antikainen, Riitta %A Hänninen, Tuomo %A Levälahti, Esko %A Laatikainen, Tiina %A Lindström, Jaana %A Paajanen, Teemu %A Peltonen, Markku %A Khalsa, Dharma Singh %A Wolozin, Benjamin %A Strandberg, Timo %A Tuomilehto, Jaakko %A Soininen, Hilkka %A Kivipelto, Miia %A Solomon, Alina %X

Leukocyte telomere length (LTL) is a biomarker of aging, and it is associated with lifestyle. It is currently unknown whether LTL is associated with the response to lifestyle interventions. The goal is to assess whether baseline LTL modified the cognitive benefits of a 2-year multidomain lifestyle intervention (exploratory analyses). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2-year randomized controlled trial including 1,260 people at risk of cognitive decline, aged 60-77 years identified from the general population. Participants were randomly assigned to the lifestyle intervention (diet, exercise, cognitive training, and vascular risk management) and control (general health advice) groups. Primary outcome was change in cognition (comprehensive neuropsychological test battery). Secondary outcomes were changes in cognitive domains: memory, executive functioning, and processing speed. 775 participants (392 control, 383 intervention) had baseline LTL (peripheral blood DNA). Mixed effects regression models with maximum likelihood estimation were used to analyze change in cognition as a function of randomization group, time, baseline LTL, and their interaction. Intervention and control groups did not significantly differ at baseline. Shorter LTL was related to less healthy baseline lifestyle. Intervention benefits on executive functioning were more pronounced among those with shorter baseline LTL (p-value for interaction was 0.010 adjusted for age and sex, and 0.007 additionally adjusted for baseline lifestyle factors). The FINGER intervention cognitive benefits were more pronounced with shorter baseline LTL, particularly for executive functioning, indicating that the multidomain lifestyle intervention was especially beneficial among higher-risk individuals.

%B J Alzheimers Dis %V 59 %P 1459-1470 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/28777749?dopt=Abstract %R 10.3233/JAD-170123 %0 Journal Article %J J Alzheimers Dis %D 2017 %T BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function. %A Håkansson, Krister %A Ledreux, Aurélie %A Daffner, Kirk %A Terjestam, Yvonne %A Bergman, Patrick %A Carlsson, Roger %A Kivipelto, Miia %A Winblad, Bengt %A Granholm, Ann-Charlotte %A Mohammed, Abdul Kadir H %X

Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.

%B J Alzheimers Dis %V 55 %P 645-657 %G ENG %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27716670?dopt=Abstract %R 10.3233/JAD-160593 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Development of a Late-Life Dementia Prediction Index with Supervised Machine Learning in the Population-Based CAIDE Study. %A Pekkala, Timo %A Hall, Anette %A Lötjönen, Jyrki %A Mattila, Jussi %A Soininen, Hilkka %A Ngandu, Tiia %A Laatikainen, Tiina %A Kivipelto, Miia %A Solomon, Alina %X

BACKGROUND AND OBJECTIVE: This study aimed to develop a late-life dementia prediction model using a novel validated supervised machine learning method, the Disease State Index (DSI), in the Finnish population-based CAIDE study.

METHODS: The CAIDE study was based on previous population-based midlife surveys. CAIDE participants were re-examined twice in late-life, and the first late-life re-examination was used as baseline for the present study. The main study population included 709 cognitively normal subjects at first re-examination who returned to the second re-examination up to 10 years later (incident dementia n = 39). An extended population (n = 1009, incident dementia 151) included non-participants/non-survivors (national registers data). DSI was used to develop a dementia index based on first re-examination assessments. Performance in predicting dementia was assessed as area under the ROC curve (AUC).

RESULTS: AUCs for DSI were 0.79 and 0.75 for main and extended populations. Included predictors were cognition, vascular factors, age, subjective memory complaints, and APOE genotype.

CONCLUSION: The supervised machine learning method performed well in identifying comprehensive profiles for predicting dementia development up to 10 years later. DSI could thus be useful for identifying individuals who are most at risk and may benefit from dementia prevention interventions.

%B J Alzheimers Dis %V 55 %P 1055-1067 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27802228?dopt=Abstract %R 10.3233/JAD-160560 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Estradiol and Cognition in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Cohort Study. %A Imtiaz, Bushra %A Tolppanen, Anna Maija %A Solomon, Alina %A Soininen, Hilkka %A Kivipelto, Miia %X

Cardiovascular Risk factors, Aging and Dementia (CAIDE) is a Finnish population-based study. 731 cognitively normal women had self-reported hormone therapy (HT) data in 1998 as: no use, use ≤5 years, and >5 years. Information on type of HT was only available from 1995-1998 (Prescription Register). Cognition was assessed in 1998 and 2005-2008. Long-term (>5 years) HT use, especially use of estradiol alone among women having hysterectomy with bilateral oophorectomy, was associated with better episodic memory in 1998, but not in 2005-2008. Although a strong evidence for protective effect of estradiol on cognition was not observed in our study, improved global cognition among long-term users suggests that long-term postmenopausal HT may be beneficial for some cognitive domains.

%B J Alzheimers Dis %V 56 %P 453-458 %8 2017 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27983549?dopt=Abstract %R 10.3233/JAD-160643