| 1. |
- Allison, Samantha L, et al.
(författare)
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Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age.
- 2021
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 102, s. 151-160
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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.
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| 2. |
- Boström, Fredrik, et al.
(författare)
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CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.
- 2008
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:8, s. 1265-1271
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.
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| 3. |
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| 4. |
- Chiesa, Patrizia A, et al.
(författare)
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Association of brain network dynamics with plasma biomarkers in subjective memory complainers.
- 2020
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 88, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- Using a single integrated analysis, we examined the relationship between brain networks and molecular pathways in a cohort of elderly individuals at risk for Alzheimer's disease. In 205 subjective memory complainers (124 females, mean age: 75.7 ± 3.4), individual functional connectome was computed for a total of 3081 functional connections (set A) and 6 core plasma biomarkers of Alzheimer's disease (set B) were assessed. Partial least squares correlation analysis identified one dimension of population covariation between the 2 sets (p < 0.006), which we named bioneural mode. Five core plasma biomarkers and 190 functional connections presented bootstrap ratios greater than the critical value |1.96|. T-tau protein showed a trend toward significance (bootstrap resampling = 1.64). The salience, the language, the visuospatial, and the default mode networks were the strongest significant networks. We detected a strong association between network dynamics and core pathophysiological blood biomarkers. Innovative composite biomarkers, such as the bioneural mode, are promising to provide outcomes and better inform drug development and clinical practice for neurodegenerative diseases.
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| 5. |
- Glodzik, Lidia, et al.
(författare)
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Alzheimer's disease markers, hypertension, and gray matter damage in normal elderly.
- 2012
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 33:7
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Tidskriftsartikel (refereegranskat)abstract
- It is not well known whether Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are associated with brain damage in cognitively normal elderly. The combined influence of CSF biomarkers and hypertension (HTN) on the gray matter (GM) is also not well described. One hundred fifteen cognitively healthy subjects (mean age 62.6 ± 9.5%, 62% women) received clinical assessment, a high resolution magnetic resonance imaging (MRI), and a lumbar puncture. The CSF levels of total tau (t-tau), hyperphosphorylated tau (p-tau(231)), amyloid beta (Aβ42/Aβ40), p-tau(231)/Aβ42, and t-tau/Aβ42 were dichotomized as "high" and "low" based on accepted cut off values. Statistical parametric mapping was used to examine MRI scans for regional GM density, studied as a function of the CSF markers, HTN, and combination of both. Global and medial temporal lobe (MTL) GM was also assessed. Voxel based morphometry revealed that higher t-tau was associated with lower GM density in the precunei. Subjects with higher p-tau(231) and p-tau(231)/Aβ42 had less GM in temporal lobes. Low Aβ42/Aβ40 was related to less GM in the thalami, caudate, and midbrain. Subjects with hypertension showed more GM atrophy in the cerebellum, occipital, and frontal regions. Simultaneous presence of elevated CSF AD biomarkers and HTN was associated with more GM atrophy than either marker individually, but no interaction effects were identified. In conclusion, in normal elderly CSF tau markers were associated predominantly with lower GM estimates in structures typically affected early in the AD process. In this presymptomatic stage when no cognitive impairment is present, AD biomarkers and HTN have additive effects on gray matter damage.
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| 6. |
- Glodzik, Lidia, et al.
(författare)
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Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly.
- 2014
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 35:1
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Tidskriftsartikel (refereegranskat)abstract
- In hypertension (HTN), cerebral blood flow regulation limits are changed, and the threshold for blood pressure (BP) at which perfusion is safely maintained is higher. This shift may increase the brain's vulnerability to lower BP in subjects with vascular disease. We investigated whether longitudinal reduction in mean arterial pressure (MAP) was related to changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. The relationships among MAP, memory decline, and hippocampal atrophy were also examined. Seventy-seven subjects (age 63.4 ± 9.4, range 44-86 years; education 16.9 ± 2.1, range 10-22 years; 60% women) were assessed twice, 2 ± 0.5 years apart. At both time points, all subjects underwent full medical and neuropsychological evaluations, lumbar punctures, and magnetic resonance imaging examinations. Twenty-five subjects had HTN. Hyper- and normotensive subjects did not differ in their CSF biomarkers, hippocampal volumes (HipVs), or memory scores at baseline. In the entire study group, the increase in tau phosphorylated at threonine 181 (p-tau181) was associated with a decline in verbal episodic memory (β = -0.30, p = 0.01) and HipV reduction (β = -0.27, p = 0.02). However, longitudinal decrease in MAP was related to memory decline (β = 0.50, p = 0.01) and an increase in p-tau181 (β = -0.50, p = 0.01) only in subjects with HTN. Our findings suggest that the hypertensive group may be sensitive to BP reductions.
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| 7. |
- Glodzik, Lidia, et al.
(författare)
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Phosphorylated tau 231, memory decline and medial temporal atrophy in normal elders.
- 2011
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 32:12, s. 2131-41
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Tidskriftsartikel (refereegranskat)abstract
- Little is known whether cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) can predict both memory decline and associated longitudinal medial temporal lobe (MTL) gray matter (GM) reductions in cognitively healthy individuals. Fifty-seven normal elderly subjects received comprehensive evaluation at baseline and 2 years later. The baseline phosphorylated tau(231) (p-tau(231)), total tau, the amyloid beta (Aβ) Aβ42/Aβ40, t-tau/Aβ42 and p-tau(231)/Aβ42 ratios were examined as predictors of memory change and reductions in the global and MTL GM, determined from T1-weighted MRI. Twenty out of 57 participants experienced reduced memory performance at follow-up. The group with decreased memory performance showed higher baseline p-tau(231) (Z=-2.2, p=0.03), lower Aβ42/Aβ40 (t=-2.2 [55], p=0.04) and greater longitudinal MTL GM reductions (t([52])=-2.70, p=0.01). Higher baseline p-tau(231) was also associated with the absolute decrease in memory scores (rho=-0.30, p=0.02) and with longitudinal MTL GM reduction (F([2,52])=4.4, p=0.04, age corrected). Our results indicate that in normal individuals, elevated p-tau(231), a marker of neurofibrillary pathology is related to both a decrease in declarative memory and progressive atrophy of the MTL, suggesting its diagnostic potential in preclinical stage.
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| 8. |
- Guerreiro, Rita, et al.
(författare)
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Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 38, s. 7-214
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Tidskriftsartikel (refereegranskat)abstract
- The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
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| 9. |
- Hansson, Oskar, et al.
(författare)
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Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:2, s. 165-73
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify preclinical Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments ((133)Xe method) were performed in 70 patients with MCI who were cognitively stable for 4-6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for beta-amyloid(1-42), total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P<0.0001). Subjects with pathological levels of both CSF tau and beta-amyloid(1-42) were also at high risk of developing AD (hazard ratio 13.4, P<0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 (P<0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.
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| 10. |
- Hansson, Oskar, et al.
(författare)
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Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment.
- 2010
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:3, s. 357-67
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD). However, studies on Abeta in plasma are contradictory, and show very marginal differences between patients and controls. Here, we analyzed plasma samples using a new multiplex immunoassay for simultaneous analysis of Abeta(1-40), Abeta(n-40), Abeta(1-42), and Abeta(n-42). The plasma samples were obtained at baseline from two independent cohorts of patients with mild cognitive impairment (MCI) and age-matched controls. In the first cohort, 41% of the 117 MCI cases converted to AD during a clinical follow-up period of 4-7 years. In the second cohort, 14% of the 110 MCI subjects developed AD during a clinical follow-up period of 2-4 years. None of the plasma Abeta isoforms differed between MCI patients that subsequently developed AD and healthy controls or stable MCI patients. The Cox proportional hazards model did not reveal any differences in the probability of progression from MCI to AD related to plasma Abeta levels. In contrast, low levels of Abeta(1-42) in CSF were strongly associated with increased risk of future AD. The absence of a change in plasma Abeta in incipient AD, despite the marked change in CSF, may be explained by the lack of a correlation between the levels of Abeta(1-42) in CSF and plasma. In conclusion, the results show that CSF biomarkers are better predictors of progression to AD than plasma Abeta isoforms.
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