| 1. |
- Kivimäki, Mika, et al.
(författare)
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Body mass index and risk of dementia : Analysis of individual-level data from 1.3 million individuals
- 2018
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 14:5, s. 601-609
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. Methods: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. Results: Hazard ratios per 5-kg/m(2) increase in BMI for dementia were 0.71 (95% confidence interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. Conclusions: The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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| 2. |
- 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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| 3. |
- Lill, Christina M., et al.
(författare)
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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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| 4. |
- Lunde, Kristin Aaser, et al.
(författare)
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Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 14:10, s. 1293-1301
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionBoth polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.MethodsFour hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.ResultsA total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.DiscussionGBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.
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| 5. |
- Lövheim, Hugo, et al.
(författare)
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Herpes simplex infection and the risk of Alzheimer's disease : a nested case-control study
- 2015
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Ingår i: Alzheimer's & Dementia. - : Elsevier BV. - 1552-5260 .- 1552-5279. ; 11:6, s. 587-592
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD).METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays.RESULTS: In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019).CONCLUSION: Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.
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| 6. |
- Lövheim, Hugo, et al.
(författare)
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Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:7, s. 778-782
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)—central in the pathogenesis of AD—is a logical candidate, but studies to date have produced conflicting results on its utility.Methods: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNO-BIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42.Results: Plasma concentrations of free Aβ40 and Aβ42 did not differ between preclinical AD cases and dementia-free controls, in the full sample or in subgroups defined according to sex and age group (<60 and ≥ 60 years). The interval between sampling and AD diagnosis did not affect the results. Aβ concentrations did not change in the years preceding AD diagnosis among individuals for whom longitudinal samples were available.Discussion: Plasma concentrations of free Aβ could not predict the development of clinical AD, and Aβ concentrations did not change in the years preceding AD diagnosis in this sample. These results indicate that free plasma Aβ is not a useful biomarker for the identification of individuals at risk of developing clinical AD.
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| 7. |
- Lövheim, Hugo, et al.
(författare)
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Reactivated herpes simplex infection increases the risk of Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 11:6, s. 593-599
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies have suggested a link between herpes simplex virus (HSV) type 1 and the development of Alzheimer's disease (AD).METHODS: The present analysis included 3432 persons (53.9% women, mean age at inclusion 62.7 ± 14.4 years) with a mean follow-up time of 11.3 years. The number of incident AD cases was 245. Serum samples were analyzed for anti-HSV antibodies (immunoglobulin (Ig)G and IgM) by enzyme-linked immunosorbent assays.RESULTS: The presence of anti-HSV IgG antibodies was not associated with an increased risk for AD, controlled for age and sex (hazard ratio, HR, 0.993, P = .979). However, the presence of anti-HSV IgM at baseline was associated with an increased risk of developing AD (HR 1.959, P = .012).CONCLUSION: Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.
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| 8. |
- Mohr, Wiebke, et al.
(författare)
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Key components of person-centered care for people with dementia : A systematic review of interventions to design a patient preference study
- 2021
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Ingår i: Alzheimer's & Dementia. - : Alzheimer's Association. - 1552-5260 .- 1552-5279. ; 17:S7, s. e052134-
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: To provide Person-Centered Care (PCC) for People with Dementia (PwD), patient's stated preferences must be known. Data about stated care-preferences among PwD are limited. This study aimed to identify key components of PCC for PwD by a systematic review of PCC-interventions, to inform the construction of a decision model for PwD-preference elicitation.METHOD: A protocol was registered with PROSPERO (CRD42021225084). A search of the concepts Dementia, Person-Centered Care, and Intervention was performed in PubMed, EMBASE, and Web of Science in Nov2020. Study selection was based on 2-stage screening against eligibility criteria, limited to randomized controlled trials (RCT) and nonrandomized controlled study (NRS) designs. Risk of bias was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB2) and the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Information about authors, interventions, and outcomes were extracted and entered into an "Effects Table". The identified PCC-interventions were thus synthesized into intervention categories to form key components of PCC.RESULT: Searches identified 1781 records. 19 studies (15 RCT, 4 NRS) were included after screening. The quality of the studies varied between low to moderate. The individual interventions covered a wide range of non-pharmacological, psychosocial offers, oftentimes bundled in multi-component intervention-sets. Nine intervention categories, i.e. key components of PCC to inform the construction of a decision model for PwD-preference elicitation, emerged from data synthesis: sensory enhancement/relaxation, social contact, cognitive training, validation and reminiscence, physical activities, environmental adjustments, caregiver training and support, care organization and daily living assistance. Effect measures included i.a. agitation, quality of life, antipsychotic use, depression, neuropsychiatric symptoms and behavior, with mixed results concerning the effect of the PCC interventions. All studies were conducted in nursery home or hospital settings.CONCLUSION: Nine intervention categories as key components of PCC to inform the construction of a decision model for PwD-preference elicitation could be identified. As the findings were limited to nursery home and hospital settings, community-dwelling PwD and the primary care-setting should find greater consideration for future investigations on PCC interventions and patient preference studies.
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| 9. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Elevated plasma neurofilament light in aging reflects brain white-matter alterations but does not predict cognitive decline or Alzheimer's disease
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWe investigated neurofilament light (NFL) accumulation in normal aging as well as in preclinical and clinical Alzheimer's disease (AD) and assessed individual differences in NFL load in relation to cognition and brain white-matter integrity. MethodsWe analyzed longitudinal data covering 30 years (1988-2017). Cognitive testing was done up to six times. Plasma NFL was quantified for controls and 142 cases who developed AD over time, and longitudinal changes in NFL were quantified for 100 individuals with three brain-imaging sessions. ResultsLongitudinal analyses revealed age-related NFL increases with marked variability. AD cases had elevated NFL levels, while no significant group differences were seen in the preclinical phase. Variability in NFL levels showed non-significant correlations with cognition but was associated with brain white matter. DiscussionOur findings suggest that elevated blood NFL, likely reflecting brain white-matter alterations, characterizes clinical AD, while NFL levels do not predict age-related cognitive impairment or impending AD.
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| 10. |
- Rosenberg, Anna, et al.
(författare)
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Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics : The FINGER trial
- 2018
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Ingår i: Alzheimer's & Dementia. - New York : Elsevier. - 1552-5260 .- 1552-5279. ; 14:3, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses.Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia.
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