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- Babulal, Ganesh M, et al.
(författare)
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Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.
- 2019
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:2, s. 292-312
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.
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| 2. |
- Mielke, Michelle M, et al.
(författare)
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Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease.
- 2014
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 35:11, s. 2486-94
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Tidskriftsartikel (refereegranskat)abstract
- Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but invivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with AβX-38 (r= 0.312, p= 0.003), AβX-40 (r= 0.327, p= 0.002), and T-tau (r= 0.313, p= 0.003) but not with AβX-42 (r= 0.171, p= 0.106) or p-tau (r= 0.086, p= 0.418). All sphingomyelin species correlated (most p < 0.001) with all Aβ species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest invivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Aβ and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis.
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| 3. |
- Teunissen, Charlotte E, et al.
(författare)
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Blood-based biomarkers for Alzheimer's disease: towards clinical implementation.
- 2022
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Ingår i: The Lancet. Neurology. - 1474-4465 .- 1474-4422. ; 21:1, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- For many years, blood-based biomarkers for Alzheimer's disease seemed unattainable, but recent results have shown that they could become a reality. Convincing data generated with new high-sensitivity assays have emerged with remarkable consistency across different cohorts, but also independent of the precise analytical method used. Concentrations in blood of amyloid and phosphorylated tau proteins associate with the corresponding concentrations in CSF and with amyloid-PET or tau-PET scans. Moreover, other blood-based biomarkers of neurodegeneration, such as neurofilament light chain and glial fibrillary acidic protein, appear to provide information on disease progression and potential for monitoring treatment effects. Now the question emerges of when and how we can bring these biomarkers to clinical practice. This step would pave the way for blood-based biomarkers to support the diagnosis of, and development of treatments for, Alzheimer's disease and other dementias.
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| 4. |
- Tian, Qu, et al.
(författare)
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Association of Dual Decline in Memory and Gait Speed With Risk for Dementia Among Adults Older Than 60 Years A Multicohort Individual-Level Meta-analysis
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Question Is a decline in both memory and gait speed with aging associated with a higher risk of dementia than no decline or a decline in memory or gait only in older adults? Findings In this meta-analysis of 6 studies including 8699 participants from the United States and Europe, a decline in both memory and gait was associated with 6.28 times higher risk of developing dementia than no decline. Meaning Older adults without dementia with parallel declines in memory and gait are associated with high risk of developing dementia and may be a group to target for prevention. This meta-analysis assesses whether parallel declines in memory and gait speed among older adults, compared with those who experience no decline or decline in either memory or gait speed only, are associated with risk of developing dementia. Importance Dual decline in both memory and gait speed may characterize a group of older individuals at high risk for future dementia. Objective To assess the risk of dementia in older persons who experience parallel declines in memory and gait speed compared with those who experience no decline or decline in either memory or gait speed only. Design, Setting, and Participants A multicohort meta-analysis was performed of 6 prospective cohort studies conducted between 1997 and 2018 in the United States and Europe. Participants were 60 years or older, had an initial gait speed of more than 0.6 m/s (ie, free of overt dismobility), with repeated measures of memory and gait speed before dementia diagnosis during a mean follow-up of 6.6 to 14.5 years. Within each study, participants were divided into 4 groups: memory decline only, gait speed decline only, dual decline, or no decline (hereafter referred to as usual agers). Gait decline was defined as a loss of 0.05 m/s or more per year; memory decline was defined as being in the cohort-specific lowest tertile of annualized change. Main Outcomes and Measures Risk of incident dementia according to group membership was examined by Cox proportional hazards regression with usual agers as the reference, adjusted for baseline age, sex, race/ethnicity, educational level, study site, and baseline gait speed and memory. Results Across the 6 studies of 8699 participants, mean age ranged between 70 and 74 years and mean gait speed ranged between 1.05 and 1.26 m/s. Incident dementia ranged from 5 to 21 per 1000 person-years. Compared with usual agers, participants with only memory decline had 2.2 to 4.6 times higher risk for developing dementia (pooled hazard ratio, 3.45 [95% CI, 2.45-4.86]). Those with only gait decline had 2.1 to 3.6 times higher risk (pooled hazard ratio, 2.24 [95% CI, 1.62-3.09]). Those with dual decline had 5.2 to 11.7 times the risk (pooled hazard ratio, 6.28 [95% CI, 4.56-8.64]). Conclusions and Relevance In this study, dual decline of memory and gait speed was associated with increased risk of developing dementia among older individuals, which might be a potentially valuable group for preventive or therapeutic interventions. Why dual decline is associated with an elevated risk of dementia and whether these individuals progress to dementia through specific mechanisms should be investigated by future studies.
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| 7. |
- Mielke, Michelle M, et al.
(författare)
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Comparison of variables associated with cerebrospinal fluid neurofilament, total-tau, and neurogranin.
- 2019
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 15:11, s. 1437-1447
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Tidskriftsartikel (refereegranskat)abstract
- Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total-tau [T-tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging-Alzheimer's Association Research Framework.We examined, in a community-based population (N=777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays.Multiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status.Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.
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| 8. |
- Kern, Silke, et al.
(författare)
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Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.
- 2019
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 76:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau).To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations.The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid.Risk of MCI.At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI.Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
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