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The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60-77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer's disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group × CAIDE change interaction β coefficient = -0.40, p = .02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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.

Objective: We investigated the association between late-life cynical distrust and incident dementia and mortality (mean follow-up times of 8.4 and 10.4 years, respectively) in the Cardiovascular Risk Factors, Aging and Dementia Study., Methods: Cynical distrust was measured based on the Cook-Medley Scale and categorized into tertiles. Cognitive status was evaluated with a 3-step protocol including screening, clinical phase, and differential diagnostic phase. Dementia was diagnosed according to DSM-IV criteria. Complete data on exposure, outcome, and confounders were available from 622 persons (46 dementia cases) for the dementia analyses and from 1,146 persons (361 deaths) for the mortality analyses. Age, sex, systolic blood pressure, total cholesterol, fasting glucose, body mass index, socioeconomic background, smoking, alcohol use, self-reported health, and APOE genotype were considered as confounders., Results: Cynical distrust was not associated with dementia in the crude analyses, but those with the highest level of cynical distrust had higher risk of dementia after adjusting for confounders (relative risk 3.13; 95% confidence interval [CI] 1.15-8.55). Higher cynical distrust was associated with higher mortality in the crude analyses (hazard ratio 1.40; 95% CI 1.05-1.87) but the association was explained by confounders (adjusted hazard ratio 1.19; 95% CI 0.86-1.61)., Conclusions: Higher cynical distrust in late life was associated with higher mortality, but this association was explained by socioeconomic position, lifestyle, and health status. Association between cynical distrust and incident dementia became evident when confounders were considered. This novel finding suggests that both psychosocial and lifestyle-related risk factors may be modifiable targets for interventions. We acknowledge the need for larger replication studies., (© 2014 American Academy of Neurology.)

Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but α-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease., Objective: To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) and incidence of cognitive impairment in a population-based study., Design: A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders., Results: The risk of cognitive impairment was lower in subjects in the middle tertile of the γ-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-γ-tocopherol/γ-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of γ-tocopherol, β-tocotrienol, and total tocotrienols., Conclusions: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans., (© 2013.)

We assessed midlife blood pressure (BP), body mass index, total cholesterol, and their changes over time in relation to cortical thickness on magnetic resonance imaging 28 years later in 63 elderly at risk of dementia. Participants in the population-based Cardiovascular Risk Factors, Aging, and Dementia study were first examined at midlife. A first follow-up was conducted after 21 years, and a second follow-up after an additional 7 years. Magnetic resonance images from the second follow-up were analyzed using algorithms developed at McGill University, Montreal, Canada. Midlife hypertension was related to thinner cortex in several brain areas, including insular, frontal, and temporal cortices. In elderly with thinner insular cortex, there was a continuous decline in systolic BP and an increase in pulse pressure after midlife, while in elderly with thicker insular cortex the decline in systolic BP started at older ages, paralleled by a decline in pulse pressure. No associations were found between body mass index, cholesterol, or apolipoprotein E ε4 allele and cortical thickness in this group of elderly at risk individuals., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2‐year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well‐established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies. [ABSTRACT FROM AUTHOR]

Introduction: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at risk for dementia. Brain integrity was appraised throughout structural measures (magnetic resonance imaging, MRI) and amyloid accumulation (Pittsburgh compound B (PiB)-positron emission tomography, PiB-PET). Methods: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample – MRI (N = 126), PiB-PET (N = 41) – were included in a post hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer's disease signature (ADS) cortical thickness (FreeSurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the neuropsychological test battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, and occupational complexity, measures of brain integrity, and their interaction terms as predictors. Results: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association). Conclusions: Among individuals at risk for dementia, occupational complexity does not seem to contribute toward resilience against neuropathology. These exploratory findings require validation in larger populations. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to describe how the first phase of the coronavirus disease 2019 (COVID-19) pandemic affected older persons from the general Finnish population who are at risk of developing or have cognitive impairment, specifically, to describe whether participants experienced a change in risk factors that are relevant for the prevention of cognitive decline including diet, physical activity, access to medical care, socially and cognitively stimulating activities, and emotional health and well-being. Method: A postal survey was sent in June 2020 to 859 participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), an ongoing longitudinal study. The survey was developed to assess the effect of the COVID-19 pandemic and related infection-control measures on daily life, specifically commitment to distancing measures, access to health care and social services, daily activities, and changes in cognitive and social activities. Results: By September 2020, 613 (71%) participants responded (mean age = 77.7 years, 32% lived alone, and 80% had at least one chronic condition). Three quarters adopted some distancing practices during the first months of the pandemic. Older participants were more likely to practice total isolation than younger ones (29 vs. 19%; p = 0.003). Non-acute health-care visits were canceled for 5% of the participants who needed appointments, but cancellations in dental health care (43%), home aid (30%), and rehabilitative services (53%) were more common. Pandemic-related changes were reported in social engagements, for example, less contact with friends (55%) and family (31%), or less frequent attendance in cultural events (38%) or associations (25%), although remote contact with others increased for 40%. Feelings of loneliness increased for 21%, particularly those who were older (p = 0.023) or living alone (p < 0.001). Physical activity reduced for 34%, but dietary habits remained stable or improved. Pandemic-related changes in lifestyle and activities were more evident among those living alone. Conclusions: Finnish older persons generally reported less negative changes in lifestyles and behaviors during the pandemic than expected. Older people and those living alone seemed more susceptible to negative changes. It is important to compare how coping strategies may compare with other European countries to identify factors that may help older individuals to maintain healthy lifestyles during future waves of COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We evaluated the diagnostic potential of 24S-hydroxycholesterol (24OHC) in cerebrospinal fluid. At a memory clinic, we investigated subjects with subjective cognitive impairment (SCI, n = 33), mild cognitive impairment (MCI) patients (n = 27), MCI patients with later progression into Alzheimer dementia at follow up (n = 10), and patients with AD (n = 24). We also had a control group of healthy volunteers who did not later develop cognitive problems (n = 13). The fraction of the population with pathological levels of 24OHC was 8% in controls, 34% in SCI, 37% in MCI, 80% in MCI with progression, and 42% in AD. The corresponding fractions for T-tau, P-tau, and Aβ42 were lower in the case of SCI and MCI but higher in the case of controls and AD. In case of MCI with progression, the fraction of pathological levels of 24OHC and Aβ42 were 80% and 63% respectively. We also studied a population of old healthy subjects age 75-99 years (n = 25). The fraction of individuals in this population with pathological levels of 24OHC was 0% whereas the fraction of individuals with pathological level of at least one of the other three biomarkers was 40%. The diagnostic power of 24OHC in cerebrospinal fluid seems to be similar to or lower than that of the established biomarkers T-tau, P-tau, and Aβ42 in the diagnosis of established AD. Our data suggest that 24OHC may be more sensitive than the classical biomarkers in an early phase of the neurodegenerative process and a better marker for 'brain health' in old age. [ABSTRACT FROM AUTHOR]

Abstract: Evidence was recently presented from in vitro studies that 24S-hydroxycholesterol acts as a signalling molecule inducing apoE-mediated cholesterol efflux from astrocytoma cells, and that there is a direct effect of the oxysterol on apoE transcription, protein synthesis and secretion. Consistent with this mechanism, a significant correlation is demonstrated here between levels of apoE and 24S-hydroxycholesterol in cerebrospinal fluid from patients with Alzheimer''s disease and patients with mild cognitive impairment. Such a correlation was not found in control patients. There was no correlation between levels of apoE and cholesterol in cerebrospinal fluid from controls. The results are consistent with a close coupling between release of 24S-hydroxycholesterol and apoE secretion under conditions with neuronal degeneration. The levels of apoE in cerebrospinal fluid were also correlated to the levels of Tau and the possibility is discussed that the level of apoE in cerebrospinal fluid may be used as a marker of neurodegeneration. [Copyright &y& Elsevier]

The authors discuss research on risk prediction models for identification of individuals with increased risk of future cognitive impairment. They reference the study "Predicting the Risk of Mild Cognitive Impairment in the Mayo Clinic Study of Aging" by V. S. Pankratz and colleagues published in the journal "Neurology" in 2015. Topics covered include the growth in interest in dementia risk prediction as well as the prognostic models for dementia prevention.