•We compared the distribution of WMHs across eleven neurodegenerative disease groups.•Our results show greater WMH burden in all cognitively impaired and dementia groups compared with controls.•Women ...tended to have lower WMH loads than men.•There were consistent asymmetric patterns in frontal and occipital lobes.
White matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders.
Data included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimer’s dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinson’s disease (PD-CIE), cognitively impaired Parkinson’s disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women.
All cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH volumes than the left.
There were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.
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Abstract Background This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating ...procedures for magnetic resonance (MR)-based manual hippocampal segmentation. Methods The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. Results Agreement was significant on the inclusion of alveus/fimbria ( P = .021), whole hippocampal tail ( P = .013), medial border of the body according to visible morphology ( P = .0006), and on this combined set of features ( P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer’s disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. Discussion Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.
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Introduction
Cognitive decline in Alzheimer's disease is associated with amyloid beta (Aβ) accumulation, neurodegeneration, and cerebral small vessel disease, but the temporal relationships among ...these factors is not well established.
Methods
Data included white matter hyperintensity (WMH) load, gray matter (GM) atrophy and Alzheimer's Disease Assessment Scale‐Cognitive‐Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1–42) for 461 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships among baseline WMH, GM, and Aβ1–42 to changes in WMH, GM, Aβ1–42, and cognition at 1‐year follow‐up.
Results
Baseline WMHs and Aβ1–42 predicted WMH increase and GM atrophy. Baseline WMHs and Aβ1–42 predicted worsening cognition. Only baseline Aβ1–42 predicted change in Aβ1–42.
Discussion
Baseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1–42 predicted WMH increase, suggesting a potential role of amyloid in WM damage.
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Évaluation complète d’une étude de cohorte canadienne portant sur la démence et la neuro-dégénérescence. Contexte : L’évaluation globale de la neuro-dégénérescence et de la démence (COMPASS-ND), ...étude de cohorte du Consortium canadien en neuro-dégénérescence associée au vieillissement (CCNV), représente une initiative nationale visant à promouvoir la recherche portant sur la démence et à soutenir les programmes de recherche des équipes du CCNV. Totalisant 2310 sujets recrutés partout au pays, cette cohorte longitudinale regroupe des individus fortement « phénotypés » qui présentent diverses formes de démence et de pertes de mémoire légères. En plus de sujets âgés dont les fonctions cognitives sont intactes, ces 2310 sujets ont permis de valider les hypothèses formulées par les équipes du CCNV. Méthodes : Nous avons utilisé de nombreux documents pour décrire cette étude : le protocole de la COMPASS-ND ; la demande initiale de subvention ; le cinquième rapport d’étape semi-annuel du CCNV soumis aux Instituts de recherche en santé du Canada (IRSC) en décembre 2017 ; ainsi que d’autres documents produits à la suite de modifications consécutives à la mise en œuvre de ce projet. Résultats : L’étude de cohorte COMPASS-ND du CCNV inclut des participants de partout au Canada dont les divers états cognitifs sont associés à des maladies neurodégénératives ou au risque d’en souffrir. Ils feront l’objet d’un large éventail d’examens expérimentaux, cliniques, génétiques et d’imagerie afin d’aborder de manière spécifique les causes, le diagnostic, le traitement et la prévention de ces états cognitifs chez les personnes âgées. Les données obtenues à la suite d’évaluations cliniques et cognitives, ainsi que celles issues d’échantillons biologiques, d’imagerie cérébrale, de tests génétiques et de dons de cerveaux, seront utilisées pour tester les hypothèses générées par les équipes de recherche du CCNV et d’autres chercheurs canadiens. Cette étude constitue donc à ce jour l’étude canadienne la plus complète et la plus ambitieuse au sujet de la démence. La présentation des données initiales ayant eu lieu en 2018, la cohorte devrait atteindre sa taille maximale d’ici à 2020.Conclusion : La disponibilité des données de l’étude COMPASS-ND stimulera considérablement la recherche sur la démence au Canada au cours des prochaines années.
Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A ...terrestrial model for this is head‐down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14‐day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55–65 underwent baseline measurements, 14 days of −6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well‐being and aiding bedrest‐bound older adults. By outlining evidence‐based interventions, this research supports both space travellers and those enduring prolonged bedrest.
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•A new paradigm for performing post-mortem MRI-histology studies of the human brain.•MRI of the ex vivo brain after fixation of the body by perfusion.•We propose in situ fixation, ...allowing study of the brain with MRI for several months.•The proposed method preserves the in vivo anatomical features in the ex-vivo MRI.•The antigenicity of the tissue is well preserved after months of perfusion fixation.
MRI-histology correlation studies of the ex vivo brain mostly employ fresh, extracted (ex situ) specimens, aldehyde fixed by immersion, which has several disadvantages for MRI scanning (e.g. deformation of the organ). A minority of studies are done ex vivo-in situ (unfixed brain), requiring an MRI scanner readily available within a few hours of the time of death.
We propose a new technique, exploited by anatomists, for scanning the ex vivo brain: fixation by whole body perfusion, which implies fixation of the brain in situ. This allows scanning the brain surrounded by fluids, meninges, and skull, preserving the structural relationships of the brain in vivo.
To evaluate the proposed method, five heads perfused-fixed with a saturated sodium chloride solution were employed. Three sequences were acquired on a 1.5 T MRI scanner: T1weighted, T2weighted-FLAIR, and Gradient-echo. Histology analysis included immunofluorescence for myelin basic protein and neuronal nuclei.
All MRIs were successfully processed through a validated pipeline used with in vivo MRIs. All cases exhibited positive antigenicity for myelin and neuronal nuclei.
All scans registered to a standard neuroanatomical template in pseudo-Talairach space more accurately than an ex vivo-ex situ scan.
The time interval to scan the ex vivo brain in situ was increased to at least 10 months.
MRI and histology study of the ex vivo-in situ brain fixed by perfusion is an alternative approach that has important procedural and practical advantages over the two standard methods to study the ex vivo brain.
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This study examined childhood socioeconomic status (SES) as a predictor of later life cognitive decline. Data came from 519 participants in the Lothian Birth Cohort 1936 (LBC1936) study. SES measures ...at 11 years of age included parental educational attainment, father's occupational status, household characteristics and a composite measure of global childhood SES (i.e., a total of low SES childhood indicators). Cognitive abilities were assessed by the Mini-Mental State Exam at ages 69.8, 72.8 and 76.7 years. Most indicators of low childhood SES (i.e., father manual worker, less than secondary school father education, household overcrowding, exterior located toilet, and global childhood SES) did not predict cognitive decline between the ages of 69.8 and 76.7. Participants with less educated mothers showed an increase in cognitive decline (
= -0.132,
= 0.048, and CI = -0.80, -0.00). The relationship between maternal educational attainment and cognitive decline became non-significant when controlling for adult SES (i.e., participant educational attainment and occupation). Adult SES did not mediate the latter relationship. This study provides new evidence that childhood SES alone is not strongly associated with cognitive decline. New knowledge is critical to improving population health by identifying life span stages in which interventions might be effective in preventing cognitive decline.
•Higher reserve scores relate to activation of the right inferior temporal gyri.•Higher reserve scores relate to activation of the left occipital fusiform gyri.•The temporal activation moderates the ...effect of hippocampal volume on memory.•Recruitment of the temporal lobe protects against hippocampal atrophy.•Temporal activation supports cognitive reserve to sustains memory performance.
Cognitive reserve can be defined as a property of the brain that enables an individual to sustain cognitive performance in spite of age-related neural changes. This study uses brain imaging to identify which cognitive reserve mechanisms protect against the detrimental effect of hippocampal atrophy on associative memory.
The study included 108 older adults from the Quebec Consortium for the early identification of Alzheimer’s disease. They received a magnetic resonance imaging examination to measure memory-related activations and hippocampal volume. Participants also completed a reserve-proxy questionnaire, and received a comprehensive clinical assessment.
Higher scores on the reserve questionnaire were associated with more activation in the right inferior temporal and left occipital fusiform gyri. The activation of the right temporal gyrus moderated the relationship between the volume of the hippocampus and face-name memory. A smaller volume was associated with weaker memory in participants with lower activation, but not in those with greater activation.
Recruitment of the temporal lobe protects against the detrimental effect of hippocampal atrophy on associative memory and contributes to cognitive reserve.
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This systematic review examined the longitudinal association between amyloid-β (Aβ) accumulation and cognitive decline in cognitively healthy adults. It was conducted using the PubMed, Embase, ...PsycInfo, and Web of Science databases. The methodological quality of the selected articles was assessed. In fine, seventeen longitudinal clinical studies were included in this review. A minority (seven out of 17) of studies reported a statistically significant association or prediction of cognitive decline with Aβ change, measured by positron emission tomography (PET; n = 6) and lumbar puncture (n = 1), with a mean follow-up duration of 3.17 years for cognition and 2.99 years for Aβ. The studies reporting significant results with PET found differences in the frontal, posterior cingular, lateral parietal and global (whole brain) cortices as well as in the precuneus. Significant associations were found with episodic memory (n = 6) and global cognition (n = 1). Five of the seven studies using a composite cognitive score found significant results. A quality assessment revealed widespread methodological biases, such as failure to report or account for loss-to follow up and missing data, and failure to report p-values and effect sizes of non-significant results. Overall, the longitudinal association between Aβ accumulation and cognitive decline in preclinical Alzheimer’s disease remains unclear. The discrepancy in results between studies may be explained in part by the choice of neuroimaging technique used to measure Aβ change, the duration of longitudinal studies, the heterogeneity of the healthy preclinical population, and importantly, the use of a composite score to capture cognitive changes with increased sensitivity. More longitudinal studies with larger sample sizes are needed to elucidate this relationship.
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Abstract Background The promise of Alzheimer’s disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to ...widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer’s disease and thus represents the most rational target for an initial effort at standardization. Methods and Results The authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer’s Disease Centers–Alzheimer’s Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer’s Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark. Conclusions Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers.
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