| 1. |
- Van Asbroeck, Stephanie, et al.
(författare)
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Lifestyle and incident dementia: A COSMIC individual participant data meta-analysis
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279. ; 20:6, s. 3972-3986
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONThe LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODSWe combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTSA one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged <= 75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSIONModifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.
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| 2. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 3. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 20:2, s. 1239-1249
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Tidskriftsartikel (refereegranskat)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changesand those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaβeta Brain Research Center's Alzheimer's At-Risk Cohort [β-AARC]).UGOT p-tau217 showed high accuracy (area under the curve [AUC]=0.80-0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC=0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 4. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (β-AARC).UGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aβ pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC= 0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 5. |
- Pascoal, Tharick, et al.
(författare)
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Astrocyte reactivity influences the association of amyloid-β and tau biomarkers in preclinical Alzheimer's disease.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes are key to unleashing Aβ effects in pathological tau phosphorylation. In a large study ( n =1,016) across three cohorts, we tested whether astrocyte reactivity modulates the association of Aβ with plasma tau phosphorylation in CU people. We found that Aβ pathology was associated with increased plasma phosphorylated tau levels only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau-PET analysis revealed that tau tangles accumulated as a function of Aβ burden only in CU Ast+ individuals with a topographic distribution compatible with early AD. Our findings suggest that increased astrocyte reactivity is an important upstream event linking Aβ burden with initial tau pathology which might have implications for the biological definition of preclinical AD and for selecting individuals for early preventive clinical trials.
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| 6. |
- Peters, Ruth, et al.
(författare)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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