| 1. |
- Vuorinen, Miika, et al.
(författare)
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Changes in vascular factors 28 years from midlife and late-life cortical thickness
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Mangialasche, Francesca, et al.
(författare)
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Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults
- 2013
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:12, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but a-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 (alpha-tocopherylquinone, 5-nitro-gamma-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 8 years 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 alpha-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-gamma-tocopherol/gamma-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of gamma-tocopherol, beta-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.
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| 3. |
- Thunborg, Charlotta, 1965-, et al.
(författare)
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Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : Springer Nature. - 1758-9193. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.
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| 4. |
- Wallin, Karin, et al.
(författare)
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Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later : a population based study
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 31:3, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOE epsilon 4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD.
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| 5. |
- Norgren, Jakob, et al.
(författare)
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Capillary blood tests may overestimate ketosis : triangulation between three different measures of beta-hydroxybutyrate
- 2020
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:2, s. e184-E188
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Tidskriftsartikel (refereegranskat)abstract
- The ketone body beta-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0-1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson's r = 0.99), BHBv (r = 0.91), and BHBc (r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64-0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.
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| 6. |
- Enache, Daniela, et al.
(författare)
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CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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| 7. |
- Adedeji, Dickson O., et al.
(författare)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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| 8. |
- Kivipelto, Miia, et al.
(författare)
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The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress
- 2013
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
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| 9. |
- Overton, Marieclaire, et al.
(författare)
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Sleep disturbances and change in multiple cognitive domains among older adults: a multicenter study of five Nordic cohorts
- 2024
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Ingår i: SLEEP. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 47:3
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: We examined and compared cross-sectional and longitudinal associations between self-reported sleep disturbances and various cognitive domains in five separate Nordic European longitudinal aging studies (baseline N = 5631, mean age = 77.7, mean follow-up = 4.16 years).Methods: Comparable sleep parameters across studies included reduced sleep duration/quality, insomnia symptoms (sleep latency, waking up at night, and early awakenings), short and long sleep duration, and daytime napping. The cognitive domains were episodic memory, verbal fluency, perceptual speed, executive functioning, and global cognition (aggregated measure). A series of mixed linear models were run separately in each study and then compared to assess the level and rate of change in cognitive functioning across each sleep disturbance parameter. Models were adjusted for age, sex, education, hypnotic usage, depressive symptoms, lifestyle factors, cardiovascular, and metabolic conditions. By using a coordinated analytic approach, comparable construct-level measurements were generated, and results from identical statistical models were qualitatively compared across studies.Results: While the pattern of statistically significant results varied across studies, subjective sleep disturbances were consistently associated with worse cognition and steeper cognitive decline. Insomnia symptoms were associated with poorer episodic memory and participants sleeping less or more than 7-8 hours had a steeper decline in perceptual speed. In addition, daytime napping (>2 hours) was cross-sectionally and longitudinally associated with all examined cognitive domains. Most observed associations were study-specific (except for daytime napping), and a majority of association estimates remained significant after adjusting for covariates.Conclusion: This rigorous multicenter investigation further supports the importance of sleep disturbance, including insomnia, long and short sleep duration, and daytime napping on baseline cognitive functioning and rate of change among older adults. These sleep factors may be targeted in future lifestyle interventions to reduce cognitive decline.
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| 10. |
- Solomon, Alina, et al.
(författare)
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Prevention of Alzheimer's Disease : Backward through the Lifespan
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33, s. s465-S469
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Forskningsöversikt (refereegranskat)abstract
- This is a brief summary of experiences from Finland related to Alzheimer's disease (AD) prevention research. The first signals that AD may have vascular modifiable risk factors came from studies on cardiovascular conditions and diabetes. Cardiovascular prevention projects such as North Karelia Project and WHO-MONICA in the 1970-1980s were focused on younger populations, which led to the idea of looking for risk factors as far back as middle age. Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) is one of the few studies in the world focusing on late-life cognition with a large and representative population-based cohort, baseline examination at midlife, and follow-up time up to three decades. Since 1998, it has identified several modifiable risk factors for cognitive impairment/dementia, and produced the first risk score for estimating dementia risk based on midlife profiles. The CAIDE Dementia Risk Score has been used to select participants in the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER). FINGER is an ongoing multicenter RCT involving 1,200 participants aged 60-77 years, and testing the effects of a two-year multi-domain intervention targeting several risk factors simultaneously. It started in September 2009 and will be completed at the end of 2013. The FINGER study is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
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