Post-mortem assessment in vascular dementia: advances and aspirations

McAleese, Kirsty E.; Alafuzoff, Irina; Charidimou, Andreas; Reuck, Jacques De; Grinberg, Lea T.; Hainsworth, Atticus H.; Hortobágyi, Tibor; Ince, Paul G.; Jellinger, K. A.; Gao, Jing; Kalaria, Raj N.; Kovács, Gábor G.; Kovari, Eniko Veronika; Love, Seth; Popović, Mara; Skrobot, Olivia Anna; Taipa, Ricardo; Thal, Dietmar Rudolf; Werring, David J.; Wharton, Stephen B.; Attems, Johannes

doi:10.1186/s12916-016-0676-5

Cited by 118 publications

(103 citation statements)

References 175 publications

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“…Interestingly, SVD is also an important risk factor for large vessel disease 97 . The histopathological substrate of SVD includes lipo-hyalinization of vessels, formation of microatheromas within vessels, fibroid necrosis, enlarged Virchow–Robin spaces (eVRS), pallor of perivascular myelin, and astrocytic gliosis 98 . In addition to age-related and possibly synergistic interactions between SVD and AD pathology, cerebral amyloid angiopathy can cause a vigorous inflammatory and non-inflammatory SVD, with microbleeds and infarcts.…”

Section: Vascular Dementiamentioning

confidence: 99%

A clinicopathological approach to the diagnosis of dementia

2017

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The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes — Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases — with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms.

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Section: Vascular Dementiamentioning

confidence: 99%

A clinicopathological approach to the diagnosis of dementia

2017

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“…Thus, in future studies, a combination of DTI with MRS, a technique to investigate neurochemical alterations, may help to uncover the unmyelinated fiber axons in the cholinergic pathway. Thirdly, as demonstrated by post-mortem studies, the co-occurrence of VCI and other neurodegenerative disorders in the elderly is very frequent (McAleese et al, 2016). We could not exclude the possibility that the VCIND patients included in our study might also suffer from other confounding preclinical cognitive disorders.…”

Section: Discussionmentioning

confidence: 89%

P4‐221: White Matter Damage in Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment No Dementia

Liu

Zhu

Teipel

et al. 2016

Alzheimer's & Dementia

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Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.

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“…Ezt az állapotot incidentális LBD-nek (iLBD) hívjuk, ami feltételezhetően a korai stádiuma a manifeszt LBD-nek [23]. Az iLBD létezése megkérdője-lezi az LB-k kizárólagos kóroki szerepét és felveti, hogy a patogenezisben további járulékos tényezők (például cerebrovascularis mechanizmusok) is részt vesznek [24,25].…”

Section: Neuropatológiai Jellemzőkunclassified

A Lewy-testes demencia klinikai és neuropatológiai jellemzői

et al. 2017

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A Lewy-testes demencia a második leggyakoribb neurodegeneratív demencia. A pontos diagnózisa gyakran csak neuropatológiai vizsgálattal lehetséges. A betegség fő morfológiai jellemzője a kóros α-szinukleinben gazdag Lewy-test és Lewy-neurit -csakúgy, mint a rokon kórkép Parkinson-kór és az ahhoz társuló demencia esetén. A patomechanizmus fontos tényezői a neurotranszmitter rendszerek zavara, a szinaptikus diszfunkció és az ubikvitin-proteaszóma rendszer elégtelen működése. Jellemző a kognitív teljesítmény fluktuációja, parkinsonizmus és vizuális hallucináció. Mivel gyakran nem típusos a klinikai kép és időbeni lefolyás, a képalkotó eljárások és biomarkerek elősegíthetik a korai felismerést. Noha hatékony oki terápia nincs, életminőséget javító kezelések lehetségesek. A klinikopatológiai vizsgálatok kiemelten fontosak a patomechanizmus jobb megértése, a pontos diagnózis és a hatékony terápia érdeké-ben. Orv Hetil. 2017; 158(17): 643-652.Kulcsszavak: Lewy-testes demencia, neuropatológia, biomarkerek, Parkinson-kór, α-szinuklein Clinical and neuropathological characteristics of dementia with Lewy bodiesDementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. The accurate diagnosis is often possible only by neuropathological examination. The morphologic hallmarks are the presence of α-synuclein-rich Lewy bodies and Lewy neurites, identical to those seen in Parkinson's disease (PD) and Parkinson's disease dementia (PDD). Neurotransmitter deficits, synaptic and ubiquitin-proteasome system (UPS) dysfunction play major role in the pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism and visual hallucinations. Due to the often atypical clinical presentation novel imaging techniques and biomarkers could help the early diagnosis. Although curative treatment is not available, therapies can improve quality of life. Clinicopathological studies are important in exploring pathomechanisms, ensuring accurate diagnosis and identifying therapeutic targets.

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Post-mortem assessment in vascular dementia: advances and aspirations

Cited by 118 publications

References 175 publications

A clinicopathological approach to the diagnosis of dementia

A clinicopathological approach to the diagnosis of dementia

P4‐221: White Matter Damage in Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment No Dementia

A Lewy-testes demencia klinikai és neuropatológiai jellemzői

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