nucleus basalis of Meynert Dotaz Zobrazit nápovědu
The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer's disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39-77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.
- MeSH
- bílá hmota anatomie a histologie diagnostické zobrazování MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervové dráhy anatomie a histologie diagnostické zobrazování MeSH
- nucleus basalis Meynerti anatomie a histologie diagnostické zobrazování MeSH
- paměť fyziologie MeSH
- pars basalis telencephali anatomie a histologie diagnostické zobrazování MeSH
- pozornost fyziologie MeSH
- senioři MeSH
- sexuální faktory MeSH
- stárnutí fyziologie MeSH
- věkové faktory MeSH
- zobrazování difuzních tenzorů * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Vědecké spisy Vysokého učení technického v Brně. PhD Thesis ; sv. 20
31 s. : grafy ; 22 cm
- MeSH
- biomedicínský výzkum MeSH
- duševní poruchy patologie MeSH
- mozková kůra cytologie patologie MeSH
- neurony MeSH
- stárnutí MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- AMPA receptory antagonisté a inhibitory MeSH
- chování při pití účinky léků MeSH
- excitační aminokyseliny antagonisté a inhibitory farmakologie MeSH
- krysa rodu rattus MeSH
- mikroinjekce MeSH
- nucleus basalis Meynerti cytologie fyziologie MeSH
- valeráty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- dítě MeSH
- dospělí MeSH
- dyslexie patofyziologie MeSH
- elektroencefalografie MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- mladiství MeSH
- nucleus basalis Meynerti patofyziologie MeSH
- pohyb MeSH
- spánkový lalok fyziologie MeSH
- světlo MeSH
- zrakové evokované potenciály MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
TABLE OF CONTENTS -- Topical Highlights 2 -- Introduction 5 -- The Cholinergic Hypothesis Of Alzheimer Of Aricept™ 12 -- Inhibition of Acetylcholinesterase by ARICEPT “ 12 -- Effect of ARICEPT “ in a Model of Cognitive Dysfunction -- Resulting from Damage to the Nucleus Basalis of Meynert 12 -- Pharmacokinetics -- Of Alzheimer’s Disease 17 -- Assessment Tools for Evaluation of Patients with Alzheimer’s Disease 17 -- Clinical Trials of ARICEPT™ 19 -- Summary of ARICEPT™ Clinical Efficacy 26 -- Safety Profile Of
37 stran : ilustrace ; 28 cm
Brožura představuje lék Aricept (donepezil hydrochloride), určený k léčbě Alzheimerovy nemoci.
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- NLK Publikační typ
- brožury
Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.
- MeSH
- Alzheimerova nemoc * psychologie MeSH
- bílá hmota * MeSH
- cholinergní látky MeSH
- kognitivní dysfunkce * psychologie MeSH
- lidé MeSH
- mozek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mild cognitive impairment with the core clinical features of dementia with Lewy bodies is recognized as a prodromal stage of dementia with Lewy bodies. Although grey matter atrophy has been demonstrated in prodromal dementia with Lewy bodies, longitudinal rates of atrophy during progression to probable dementia with Lewy bodies are unknown. We investigated the regional patterns of cross-sectional and longitudinal rates of grey matter atrophy in prodromal dementia with Lewy bodies, including those who progressed to probable dementia with Lewy bodies. Patients with mild cognitive impairment with at least one core clinical feature of dementia with Lewy bodies (mean age = 70.5; 95% male), who were enrolled in the Mayo Clinic Alzheimer's Disease Research Center and followed for at least two clinical evaluations and MRI examinations, were included (n = 56). A cognitively unimpaired control group (n = 112) was matched 2:1 to the patients with mild cognitive impairment by age and sex. Patients either remained stable (n = 28) or progressed to probable dementia with Lewy bodies (n = 28) during a similar follow-up period and pathologic confirmation was available in a subset of cases (n = 18). Cross-sectional and longitudinal rates of grey matter atrophy were assessed using voxel-based and atlas-based region of interest analyses. At baseline, prodromal dementia with Lewy bodies was characterized by atrophy in the nucleus basalis of Meynert both in those who remained stable and those who progressed to probable dementia with Lewy bodies (P < 0.05 false discovery rate corrected). Increase in longitudinal grey matter atrophy rates were widespread, with greatest rates of atrophy observed in the enthorhinal and parahippocampal cortices, temporoparietal association cortices, thalamus and the basal ganglia, in mild cognitive impairment patients who progressed to probable dementia with Lewy bodies at follow-up (P < 0.05 false discovery rate corrected). Rates of inferior temporal atrophy were associated with greater rates of worsening on the clinical dementia rating-sum of boxes. Seventeen of the 18 (94%) autopsied cases had Lewy body disease. Results show that atrophy in the nucleus basalis of Meynert is a feature of prodromal dementia with Lewy bodies regardless of proximity to progression to probable dementia with Lewy bodies. Longitudinally, grey matter atrophy progresses in regions with significant cholinergic innervation, in alignment with clinical disease progression, with widespread and accelerated rates of atrophy in patients who progress to probable dementia with Lewy bodies. Given the prominent neurodegeneration in the cholinergic system, patients with prodromal dementia with Lewy bodies may be candidates for cholinesterase inhibitor treatment.
- Publikační typ
- časopisecké články MeSH
