| 1. |
- Law, Lena L, et al.
(författare)
-
Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer's disease.
- 2018
-
Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 10, s. 188-195
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected invivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD-related pathological changes. Consequently, the aim of this study was to cross-sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late-middle-aged adults at risk for AD.Eighty-five cognitively healthy late-middle-aged adults (age=64.31years, 61.2% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They wore an accelerometer (ActiGraph GT3X+) for one week to record free-living PA, yielding measures of sedentariness and various intensities of PA (i.e., light, moderate, and vigorous). They also underwent lumbar puncture to collect CSF, from which Aβ42, total tau, and phosphorylated tau were immunoassayed. Regression analyses were used to examine the association between accelerometer measures and CSF biomarkers, adjusting for age, sex, and other relevant covariates.Engagement in moderate PA was associated with higher Aβ42 (P=.008), lower total tau/Aβ42 (P=.006), and lower phosphorylated tau/Aβ42 (P=.030). In contrast, neither light nor vigorous PA was associated with any of the biomarkers. Increased sedentariness was associated with reduced Aβ42 (P=.014).In this cohort, moderate PA, but not light or vigorous, was associated with a favorable AD biomarker profile, while sedentariness was associated with greater Aβ burden. These findings suggest that a physically active lifestyle may play a protective role against the development of AD.
|
|
| 2. |
- Allison, Samantha L, et al.
(författare)
-
Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age.
- 2021
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 102, s. 151-160
-
Tidskriftsartikel (refereegranskat)abstract
- This study examined the effect of neurodegeneration, and its interaction with Alzheimer's disease (AD) cerebrospinal fluid biomarkers, on longitudinal verbal learning and memory performance in cognitively unimpaired (CU) late middle-aged adults. Three hundred and forty-two CU adults (cognitive baseline mean age=58.4), with cerebrospinal fluid and structural MRI, completed 2-10 (median=5) cognitive assessments. Learning and memory were assessed using the Rey Auditory Verbal Learning Test (RAVLT). We used sequential comparison of nested linear mixed effects models to analyze the data. Model selection preserved a significant ptau181/Aβ42×global atrophy×age interaction; individuals with less global atrophy and lower ptau181/Aβ42 levels had less learning and delayed recall decline than individuals with more global atrophy and/or higher levels of ptau181/Aβ42. The hippocampal volume×age×ptau181/Aβ42 interaction was not significant. Findings suggest that in a sample of CU late middle-aged adults, individuals with AD biomarkers, global atrophy, or both evidence greater verbal learning and memory decline than individuals without either risk factor.
|
|
| 3. |
- Jonaitis, Erin M, et al.
(författare)
-
Measuring longitudinal cognition: Individual tests versus composites.
- 2019
-
Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 11, s. 74-84
-
Tidskriftsartikel (refereegranskat)abstract
- Longitudinal cohort studies of cognitive aging must confront several sources of within-person variability in scores. In this article, we compare several neuropsychological measures in terms of longitudinal error variance and relationships with biomarker-assessed brain amyloidosis (Aβ).Analyses used data from the Wisconsin Registry for Alzheimer's Prevention. We quantified within-person longitudinal variability and age-related trajectories for several global and domain-specific composites and their constituent scores. For a subset with cerebrospinal fluid or amyloid positron emission tomography measures, we examined how Aβ modified cognitive trajectories.Global and theoretically derived composites exhibited lower intraindividual variability and stronger age × Aβ interactions than did empirically derived composites or raw scores from single tests. For example, the theoretical executive function outperformed other executive function scores on both metrics.These results reinforce the need for careful selection of cognitive outcomes in study design, and support the emerging consensus favoring composites over single-test measures.
|
|
| 4. |
- Racine, Annie M, et al.
(författare)
-
Association of longitudinal white matter degeneration and cerebrospinal fluid biomarkers of neurodegeneration, inflammation and Alzheimer’s disease in late-middle-aged adults
- 2019
-
Ingår i: Brain imaging and behavior. - : Springer Science and Business Media LLC. - 1931-7565 .- 1931-7557. ; 13:1, s. 41-52
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is characterized by substantial neurodegeneration, including both cortical atrophy and loss of underlying white matter fiber tracts. Understanding longitudinal alterations to white matter may provide new insights into trajectories of brain change in both healthy aging and AD, and fluid biomarkers may be particularly useful in this effort. To examine this, 151 late-middle-aged participants enriched with risk for AD with at least one lumbar puncture and two diffusion tensor imaging (DTI) scans were selected for analysis from two large observational and longitudinally followed cohorts. Cerebrospinal fluid (CSF) was assayed for biomarkers of AD-specific pathology (phosphorylated-tau/Aβ42 ratio), axonal degeneration (neurofilament light chain protein, NFL), dendritic degeneration (neurogranin), and inflammation (chitinase-3-like protein 1, YKL-40). Linear mixed effects models were performed to test the hypothesis that biomarkers for AD, neurodegeneration, and inflammation, or two-year change in those biomarkers, would be associated with worse white matter health overall and/or progressively worsening white matter health over time. At baseline in the cingulum, phosphorylated-tau/Aβ42 was associated with higher mean diffusivity (MD) overall (intercept) and YKL-40 was associated with increases in MD over time. Two-year change in neurogranin was associated with higher mean diffusivity and lower fractional anisotropy overall (intercepts) across white matter in the entire brain and in the cingulum. These findings suggest that biomarkers for AD, neurodegeneration, and inflammation are potentially important indicators of declining white matter health in a cognitively healthy, late-middle-aged cohort.
|
|
| 5. |
|
|
| 6. |
- Schultz, Stephanie A, et al.
(författare)
-
Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD.
- 2017
-
Ingår i: Neurology. - 1526-632X. ; 88:17, s. 1650-1658
-
Tidskriftsartikel (refereegranskat)abstract
- To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers.Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. β-Amyloid 42 (Aβ42), Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aβ42/Aβ40 and tau/Aβ42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF.A higher PRS was associated with lower Aβ42/Aβ40 (p < 0.001), higher t-tau/Aβ42 (p = 0.012), and higher p-tau/Aβ42 (p = 0.040). Furthermore, we observed PRS × CRF interactions for Aβ42/Aβ40 (p = 0.003), t-tau/Aβ42 (p = 0.003), and p-tau/Aβ42 (p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF.In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD.
|
|
| 7. |
- Schultz, Stephanie A, et al.
(författare)
-
Cardiorespiratory Fitness Attenuates the Influence of Amyloid on Cognition.
- 2015
-
Ingår i: Journal of the International Neuropsychological Society : JINS. - 1469-7661. ; 21:10, s. 841-50
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841-850).
|
|
| 8. |
- Bruno, Davide, et al.
(författare)
-
The recency ratio is related to CSF amyloid beta 1-42 levels in MCI-AD.
- 2019
-
Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 34:3, s. 415-419
-
Tidskriftsartikel (refereegranskat)abstract
- As anti-amyloid therapeutic interventions shift from enrolling patients with Alzheimer's disease (AD) dementia to individuals with pre-clinical disease, the need for sensitive measures that allow for non-invasive, fast, disseminable, and cost-effective identification of preclinical status increases in importance. The recency ratio (Rr) is a memory measure that relies on analysis of serial position performance, which has been found to predict cognitive decline and conversion to early mild cognitive impairment (MCI). The aim of this study was to test Rr's sensitivity to cerebrospinal fluid (CSF) levels of the core AD biomarkers in individuals with MCI-AD and controls.Baseline data from 126 (110 controls and 16 MCI-AD) participants from the Wisconsin Alzheimer's Disease Research Center were analysed. Partial correlations adjusting for demographics were carried out between CSF measure of amyloid beta (Aβ40, Aβ42, and the 40/42 ratio) and tau (total and phosphorylated), and memory measures (Rr, delayed recall, and total recall) derived from the Rey's Auditory Verbal Learning Test.Results indicated that Rr was the most sensitive memory score to Aβ42 levels in MCI-AD, while no memory score correlated significantly with any biomarker in controls.This study shows that Rr is a sensitive cognitive index of underlying amyloid β pathology in MCI-AD.
|
|
| 9. |
- Clark, Lindsay R, et al.
(författare)
-
Age-accelerated cognitive decline in asymptomatic adults with CSF β-amyloid.
- 2018
-
Ingår i: Neurology. - 1526-632X. ; 90:15
-
Tidskriftsartikel (refereegranskat)abstract
- Compare cognitive and hippocampal volume trajectories in asymptomatic middle-aged and older adults with positive CSF markers of β-amyloid (Aβ) or tau to adults without an Alzheimer disease (AD)-associated biomarker profile.Three hundred ninety-two adults enrolled in a longitudinal cohort study (Wisconsin Registry for Alzheimer's Prevention or Wisconsin Alzheimer's Disease Research Center) completed a lumbar puncture and at least 2 biennial or annual neuropsychological evaluations. Cutoffs for Aβ42, total tau, and phosphorylated tau were developed via receiver operating characteristic curve analyses on a sample of 78 participants (38 dementia, 40 controls). These cutoffs were applied to a separate sample of 314 cognitively healthy adults (mean age at CSF collection = 61.5 years), and mixed-effects regression analyses tested linear and quadratic interactions of biomarker group × age at each visit on cognitive and hippocampal volume outcomes.Two hundred fifteen participants (69%) were biomarker negative (preclinical AD stage 0), 46 (15%) were Aβ+ only (preclinical AD stage 1), 25 (8%) were Aβ+ and tau+ (preclinical AD stage 2), and 28 (9%) were tau+ only. Both stage 1 and stage 2 groups exhibited greater rates of linear decline on story memory and processing speed measures, and nonlinear decline on list-learning and set-shifting measures compared to stage 0. The tau+ only group did not significantly differ from stage 0 in rates of cognitive decline.In an asymptomatic at-risk cohort, elevated CSF Aβ (with or without elevated tau) was associated with greater rates of cognitive decline, with the specific pattern of decline varying across cognitive measures.
|
|
| 10. |
- Kim, Won Hwa, et al.
(författare)
-
Cerebrospinal fluid biomarkers of neurofibrillary tangles and synaptic dysfunction are associated with longitudinal decline in white matter connectivity: A multi-resolution graph analysis.
- 2019
-
Ingår i: NeuroImage. Clinical. - : Elsevier BV. - 2213-1582. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- In addition to the development of beta amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) involves the loss of connecting structures including degeneration of myelinated axons and synaptic connections. However, the extent to which white matter tracts change longitudinally, particularly in the asymptomatic, preclinical stage of AD, remains poorly characterized. In this study we used a novel graph wavelet algorithm to determine the extent to which microstructural brain changes evolve in concert with the development of AD neuropathology as observed using CSF biomarkers. A total of 118 participants with at least two diffusion tensor imaging (DTI) scans and one lumbar puncture for CSF were selected from two observational and longitudinally followed cohorts. CSF was assayed for pathology specific to AD (Aβ42 and phosphorylated-tau), neurodegeneration (total-tau), axonal degeneration (neurofilament light chain protein; NFL), and synaptic degeneration (neurogranin). Tractography was performed on DTI scans to obtain structural connectivity networks with 160 nodes where the nodes correspond to specific brain regions of interest (ROIs) and their connections were defined by DTI metrics (i.e., fractional anisotropy (FA) and mean diffusivity (MD)). For the analysis, we adopted a multi-resolution graph wavelet technique called Wavelet Connectivity Signature (WaCS) which derives higher order representations from DTI metrics at each brain connection. Our statistical analysis showed interactions between the CSF measures and the MRI time interval, such that elevated CSF biomarkers and longer time were associated with greater longitudinal changes in white matter microstructure (decreasing FA and increasing MD). Specifically, we detected a total of 17 fiber tracts whose WaCS representations showed an association between longitudinal decline in white matter microstructure and both CSF p-tau and neurogranin. While development of neurofibrillary tangles and synaptic degeneration are cortical phenomena, the results show that they are also associated with degeneration of underlying white matter tracts, a process which may eventually play a role in the development of cognitive decline and dementia.
|
|
