| 1. |
- Wuestefeld, Anika, et al.
(författare)
-
Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
-
Ingår i: Hippocampus. - 1050-9631.
-
Tidskriftsartikel (refereegranskat)abstract
- The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.
|
|
| 2. |
- Ashton, Nicholas J., et al.
(författare)
-
An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders.
- 2020
-
Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 16, s. 265-284
-
Forskningsöversikt (refereegranskat)abstract
- Cerebrospinal fluid analyses and neuroimaging can identify the underlying pathophysiology at the earliest stage of some neurodegenerative disorders, but do not have the scalability needed for population screening. Therefore, a blood-based marker for such pathophysiology would have greater utility in a primary care setting and in eligibility screening for clinical trials. Rapid advances in ultra-sensitive assays have enabled the levels of pathological proteins to be measured in blood samples, but research has been predominantly focused on Alzheimer disease (AD). Nonetheless, proteins that were identified as potential blood-based biomarkers for AD, for example, amyloid-β, tau, phosphorylated tau and neurofilament light chain, are likely to be relevant to other neurodegenerative disorders that involve similar pathological processes and could also be useful for the differential diagnosis of clinical symptoms. This Review outlines the neuropathological, clinical, molecular imaging and cerebrospinal fluid features of the most common neurodegenerative disorders outside the AD continuum and gives an overview of the current status of blood-based biomarkers for these disorders.
|
|
| 3. |
- Barthélemy, Nicolas R, et al.
(författare)
-
Highly Accurate Blood Test for Alzheimer's Disease Comparable or Superior to Clinical CSF Tests
-
Ingår i: Nature Medicine. - 1546-170X.
-
Tidskriftsartikel (refereegranskat)abstract
- With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area-under-the-curve (AUC) for both between 0.95-0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired sub-cohorts (BioFINDER-2: n=720; Knight ADRC: n=50), plasma %p-tau217 had an accuracy, positive predictive value and negative predictive value of 89-90% for Aβ PET and 87-88% for tau-PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two cut-off approach. Blood plasma %p-tau217 demonstrated performance clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.
|
|
| 4. |
- Bocancea, Diana I., et al.
(författare)
-
Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
- 2023
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:9, s. 3719-3734
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We employed a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET.In this multicenter study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease-dementia with baseline [18F]flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning.We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness.In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
|
|
| 5. |
- Groot, Colin, et al.
(författare)
-
Latent atrophy factors related to phenotypical variants of posterior cortical atrophy
- 2020
-
Ingår i: Neurology. - 1526-632X. ; 95:12, s. 1672-1685
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria (i.e., dorsal, ventral, dominant-parietal, and caudal) we assessed associations between latent atrophy factors and cognition. METHODS: We employed a data-driven Bayesian modeling framework based on latent Dirichlet allocation to identify latent atrophy factors in a multicenter cohort of 119 individuals with PCA (age 64 ± 7 years, 38% male, Mini-Mental State Examination 21 ± 5, 71% β-amyloid positive, 29% β-amyloid status unknown). The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, MRI scanner field strength, and whole-brain gray matter volume) and provides voxelwise probabilistic maps for a predetermined number of atrophy factors, allowing every individual to express each factor to a degree without a priori classification. Individual factor expressions were correlated to 4 PCA-specific cognitive domains (object perception, space perception, nonvisual/parietal functions, and primary visual processing) using general linear models. RESULTS: The model revealed 4 distinct yet partially overlapping atrophy factors: right-dorsal, right-ventral, left-ventral, and limbic. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the right-ventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-dorsal and right-ventral factors. However, individual participant profiles revealed that the large majority expressed multiple atrophy factors and had mixed clinical profiles with impairments across multiple domains, rather than displaying a discrete clinical-radiologic phenotype. CONCLUSION: Our results indicate that specific brain behavior networks are vulnerable in PCA, but most individuals display a constellation of affected brain regions and symptoms, indicating that classification into 4 mutually exclusive variants is unlikely to be clinically useful.
|
|
| 6. |
- Illán-Gala, Ignacio, et al.
(författare)
-
Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer's disease.
- 2021
-
Ingår i: Neurology. - 1526-632X. ; 96:5
-
Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically-diagnosed Alzheimer's disease (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses.We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-Tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression and survival and cortical thickness.Plasma NfL, but not plasma t-tau discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-Tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone.Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance than plasma t-tau in FTLD and AD.
|
|
| 7. |
- Leuzy, Antoine, et al.
(författare)
-
A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis
- 2021
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2295-2305
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer’s disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neurodegenerative diseases. Methods: A total of 1755 participants underwent tau PET using either [18F]flortaucipir (n = 975), [18F]RO948 (n = 493), or [18F]MK6240 (n = 287). SUVR values were calculated across four theory-driven ROIs and several tracer-specific data-driven (hierarchical clustering) regions of interest (ROIs). Diagnostic performance and cut-offs for ROIs were determined using receiver operating characteristic analyses and the Youden index, respectively. Results: Comparable diagnostic performance (area under the receiver operating characteristic curve [AUC]) was observed between theory- and data-driven ROIs. The theory-defined temporal meta-ROI generally performed very well for all three tracers (AUCs: 0.926–0.996). An SUVR value of approximately 1.35 was a common threshold when using this ROI. Conclusion: The temporal meta-ROI can be used for differential diagnosis of dementia patients with [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET with high accuracy, and that using very similar cut-offs of around 1.35 SUVR. This ROI/SUVR cut-off can also be applied across tracers to define tau positivity.
|
|
| 8. |
- Leuzy, Antoine, et al.
(författare)
-
Robustness of CSF Aβ42/40 and Aβ42/P-tau181 measured using fully automated immunoassays to detect AD-related outcomes
- 2023
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:7, s. 2994-3004
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (Aβ)42/Aβ40 or Aβ42/phosphorylated tau (p-tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)-related outcomes (i.e., Aβ-positron emission tomography [PET] visual read and AD neuropathology). Methods: We studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (Aβ-PET visual read as outcome). Using longitudinal variability in Aβ-negative controls, we identified a gray zone around cut-points where the risk of an inconsistent predicted outcome was >5%. Results: For Aβ42/Aβ40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For Aβ42/p-tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was ≈90% for both Aβ42/Aβ40 and Aβ42/p-tau181 using these cutoffs. Using Aβ-PET as an outcome, 8.7% of participants fell within a gray zone interval for Aβ42/Aβ40, compared to 4.5% for Aβ42/p-tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma Aβ42/40, the number of individuals within the gray zone was ≈1.5 to 3 times greater when using plasma Aβ42/40. Discussion: CSF Aβ42/p-tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys-based measure in clinical practice and trials.
|
|
| 9. |
- Maass, Anne, et al.
(författare)
-
Alzheimer's pathology targets distinct memory networks in the ageing brain
- 2019
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 142:8, s. 2492-2509
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer's disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20-93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer's disease dementia (65-95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer's disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = -3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = -0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer's disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer's disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function.
|
|
| 10. |
- Mattsson-Carlgren, Niklas, et al.
(författare)
-
Cerebrospinal fluid biomarkers in autopsy-confirmed Alzheimer disease and frontotemporal lobar degeneration
- 2022
-
Ingår i: Neurology. - 0028-3878. ; 98:11, s. 1137-1150
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To determine how fully automated Elecsys CSF immunoassays for β-amyloid (Aβ) and tau biomarkers and an ultrasensitive Simoa assay for neurofilament light chain (NFL) correlate with neuropathologic changes of Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We studied 101 patients with antemortem CSF and neuropathology data. CSF samples were collected a mean of 2.9 years before death (range 0.2–7.5 years). CSF was analyzed for Aβ40, Aβ42, total tau (T-tau), tau phosphorylated at amino acid residue 181 (P-tau), P-tau/Aβ42 and Aβ42/Aβ40 ratios, and NFL. Neuropathology measures included Thal phases, Braak stages, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) scores, AD neuropathologic change (ADNC), and primary and contributory pathologic diagnoses. Associations between CSF biomarkers and neuropathologic features were tested in regression models adjusted for age, sex, and time from sampling to death. Results CSF biomarkers were associated with neuropathologic measures of Aβ (Thal, CERAD score), tau (Braak stage), and overall ADNC. The CSF P-tau/Aβ42 and Aβ42/Aβ40 ratios had high sensitivity, specificity, and overall diagnostic performance for intermediate-high ADNC (area under the curve range 0.95–0.96). Distinct biomarker patterns were seen in different FTLD subtypes, with increased NFL and reduced P-tau/T-tau in FTLD–TAR DNA-binding protein 43 and reduced T-tau in progressive supranuclear palsy compared to other FTLD variants. Discussion CSF biomarkers, including P-tau, T-tau, Aβ42, Aβ40, and NFL, support in vivo identification of AD neuropathology and correlate with FTLD neuropathology.
|
|
| 11. |
- Ossenkoppele, Rik, et al.
(författare)
-
Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease : A Head-to-Head Comparison against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging
- 2021
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:8, s. 961-971
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures: Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P <.001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P <.001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P <.001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P =.71). Age (t = -2.28; P =.02), but not sex (t = 0.92; P =.36) or APOE genotype (t = 1.06; P =.29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.
|
|
| 12. |
- Ossenkoppele, Rik, et al.
(författare)
-
Assessment of Demographic, Genetic, and Imaging Variables Associated with Brain Resilience and Cognitive Resilience to Pathological Tau in Patients with Alzheimer Disease
- 2020
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:5, s. 632-642
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ϵ4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, Setting, an Participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main Outcomes and Measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ϵ4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β =-0.15, P =.02) and young patients (standardized β =-0.20, P =.006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P <.001) and global cortical thickness (standardized β = 0.23, P <.001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] =-0.235 [0.111], P =.03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and Relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.
|
|
| 13. |
- Ossenkoppele, Rik, et al.
(författare)
-
Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease
- 2020
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:2, s. 335-344
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
|
|
| 14. |
- Ossenkoppele, Rik, et al.
(författare)
-
The impact of demographic, clinical, genetic, and imaging variables on tau PET status
- 2021
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2245-2258
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.
|
|
| 15. |
- Pereira, Joana B., et al.
(författare)
-
Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults
- 2020
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. Methods: We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread. Results: We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas. Conclusions: These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.
|
|
| 16. |
- Provost, Karine, et al.
(författare)
-
Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts
- 2021
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2259-2271
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.
|
|
| 17. |
- Sexton, Claire E., et al.
(författare)
-
Novel avenues of tau research
- 2024
-
Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:3, s. 2240-2261
-
Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
|
|
| 18. |
- Singleton, Ellen H., et al.
(författare)
-
Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease
- 2020
-
Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvADbvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD
|
|
| 19. |
- Singleton, Ellen, et al.
(författare)
-
Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease
- 2021
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:8, s. 872-880
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a 'typical' memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7). Results: Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05). Conclusions: Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.
|
|
| 20. |
- Therriault, Joseph, et al.
(författare)
-
Biomarker-based staging of Alzheimer disease: rationale and clinical applications.
- 2024
-
Ingår i: Nature reviews. Neurology. - 1759-4766. ; 20:4, s. 232-244
-
Tidskriftsartikel (refereegranskat)abstract
- Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity ofAlzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.
|
|
| 21. |
- Thijssen, Elisabeth H, et al.
(författare)
-
Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.
- 2021
-
Ingår i: The Lancet. Neurology. - 1474-4465 .- 1474-4422. ; 20:9, s. 739-752
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes.In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18-99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test.Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, p<0·0001). Both p-tau217 and p-tau181 concentrations were increased in people with Alzheimer's disease syndromes (n=75, mean age 65 years [SD 10]) relative to cognitively unimpaired controls (n=118, mean age 61 years [SD 18]; AUC=0·98 [95% CI 0·95-1·00] for p-tau217, AUC=0·97 [0·94-0·99] for p-tau181; pdiff=0·31) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0·96 [0·92-1·00] for p-tau217, AUC=0·91 [0·82-1·00] for p-tau181; pdiff=0·22). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0·93 [0·91-0·96] for p-tau217, AUC=0·91 [0·88-0·94] for p-tau181; pdiff=0·01). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0·91 [0·88-0·94]) than was p-tau181 (n=214, AUC=0·89 [0·86-0·93]; pdiff=0·049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0·80 vs r=0·72; pdiff<0·0001, n=230).Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology.US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association.
|
|
| 22. |
- Wisse, Laura E.M., et al.
(författare)
-
Hippocampal subfield volumetry from structural isotropic 1 mm3 MRI scans : A note of caution
- 2021
-
Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 42:2, s. 539-550
-
Tidskriftsartikel (refereegranskat)abstract
- Spurred by availability of automatic segmentation software, in vivo MRI investigations of human hippocampal subfield volumes have proliferated in the recent years. However, a majority of these studies apply automatic segmentation to MRI scans with approximately 1 × 1 × 1 mm3 resolution, a resolution at which the internal structure of the hippocampus can rarely be visualized. Many of these studies have reported contradictory and often neurobiologically surprising results pertaining to the involvement of hippocampal subfields in normal brain function, aging, and disease. In this commentary, we first outline our concerns regarding the utility and validity of subfield segmentation on 1 × 1 × 1 mm3 MRI for volumetric studies, regardless of how images are segmented (i.e., manually or automatically). This image resolution is generally insufficient for visualizing the internal structure of the hippocampus, particularly the stratum radiatum lacunosum moleculare, which is crucial for valid and reliable subfield segmentation. Second, we discuss the fact that automatic methods that are employed most frequently to obtain hippocampal subfield volumes from 1 × 1 × 1 mm3 MRI have not been validated against manual segmentation on such images. For these reasons, we caution against using volumetric measurements of hippocampal subfields obtained from 1 × 1 × 1 mm3 images.
|
|
| 23. |
- Wood, Madeline E., et al.
(författare)
-
Sex differences in associations between APOE ε2 and longitudinal cognitive decline
- 2023
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:10, s. 4651-4661
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.
|
|
| 24. |
- Wuestefeld, Anika, et al.
(författare)
-
Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
- 2023
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 µm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.
|
|
