The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia

The Lancet Healthy Longevity, Год журнала: 2023, Номер 4(3), С. e115 - e125

Опубликована: Март 1, 2023

Язык: Английский

---

Hypertension, Neurodegeneration, and Cognitive Decline

Hypertension, Год журнала: 2024, Номер 81(5), С. 991 - 1007

Опубликована: Март 1, 2024

Elevated blood pressure is a well-established risk factor for age-related cognitive decline. Long linked to impairment on vascular bases, increasing evidence suggests potential association of hypertension with the neurodegenerative pathology underlying Alzheimer disease. Hypertension well known disrupt structural and functional integrity cerebral vasculature. However, mechanisms by which these alterations lead brain damage, enhance pathology, promote remain be established. Furthermore, critical questions concerning whether lowering antihypertensive medications prevents have not been answered. Recent developments in neurovascular biology, imaging, epidemiology, as new clinical trials, provided insights into issues. In particular, basic findings link between dysfunction pathobiology neurodegeneration shed light overlap pathology. this review, we will examine progress made relationship and, after evaluation evidence, attempt identify remaining knowledge gaps future research directions that may advance our understanding one leading health challenges time.

Язык: Английский

---

The contribution of β-amyloid, Tau and α-synuclein to blood–brain barrier damage in neurodegenerative disorders

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract Central nervous system (CNS) accumulation of fibrillary deposits made Amyloid β (A ), hyperphosphorylated Tau or α -synuclein ( -syn), present either alone in the form mixed pathology, characterizes most common neurodegenerative diseases (NDDs) as well aging brain. Compelling evidence supports that acute neurological disorders, such traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition toxic A , -syn species. While contribution these pathological proteins to neurodegeneration has been experimentally ascertained, cellular molecular mechanisms driving -syn-related damage remain be fully clarified. In last few years, studies have shown may contribute inducing and/or promoting blood–brain barrier (BBB) disruption. These can affect BBB integrity directly affecting key components pericytes endothelial cells (ECs) indirectly, macrophages activation dysfunction. Here, we summarize critically discuss findings showing how NDDs, TBI stroke. We highlight need for a deeper characterization role dysfunction macrophages, ECs improve diagnosis treatment chronic disorders.

Язык: Английский

---

Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions

International Journal of Stroke, Год журнала: 2024, Номер 19(8), С. 838 - 856

Опубликована: Сен. 16, 2024

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another vascular diseases contribute mixed picture. Therefore, the contribution affects 20 currently will increase markedly in next few decades, particularly lower- middle-income countries. In review, we discuss mechanisms cognitive impairment (VCI) review management. VCI refers spectrum pathologies any degree impairment, ranging from subjective decline, mild dementia. While acute decline occurring soon after stroke most recognized form VCI, chronic disease, particular cerebral small-vessel can cause insidious absence stroke. Moreover, disease not only commonly co-occurs Alzheimer’s (AD) increases probability AD pathology result clinical but may also etiologically development pathologies. Despite its enormous health economic impact, neglected research area, adequately powered trials therapies, resulting proven treatments. Current management emphasizes prevention treatment risk factors, evidence for intensive hypertension control. Reperfusion therapies attenuate VCI. Associated behavioral symptoms such as apathy poststroke emotionalism are common. We highlight novel strategies hopefully lead new course-modifying therapies. Finally, importance including endpoints large cardiovascular need an increased focus funding important area.

Язык: Английский

---

Towards a better diagnosis and treatment of dementia: Identifying common and distinct neuropathological mechanisms in Alzheimer's and vascular dementia

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106845 - 106845

Опубликована: Фев. 1, 2025

Язык: Английский

---

The Vascular-Immune Hypothesis of Alzheimer’s Disease

Biomedicines, Год журнала: 2023, Номер 11(2), С. 408 - 408

Опубликована: Янв. 30, 2023

Alzheimer’s disease (AD) is a devastating and irreversible neurodegenerative disorder with unknown etiology. While its cause unclear, number of theories have been proposed to explain the pathogenesis AD. In large part, these centered around potential causes for intracerebral accumulation beta-amyloid (βA) tau aggregates. Yet, persons AD dementia often exhibit autopsy evidence mixed brain pathologies including myriad vascular changes, injuries, complex inflammation, protein inclusions in addition hallmark neuropathologic lesions AD, namely insoluble βA plaques neurofibrillary tangles (NFTs). Epidemiological data demonstrate that overlapping diminish plaque NFT threshold necessary precipitate clinical dementia. Moreover, subset who pathology remain resilient while other clinically-defined do not AD-defining lesions. It increasingly recognized pathologically heterogeneous biologically multifactorial uncharacterized biologic phenomena involved genesis progression. Here, we review literature regard criteria incipient discuss converging concepts regarding immune factors

Язык: Английский

---

Current and Future Treatments of Vascular Cognitive Impairment

Stroke, Год журнала: 2024, Номер 55(4), С. 822 - 839

Опубликована: Март 25, 2024

Язык: Английский

---

Evidence against a temporal association between cerebrovascular disease and Alzheimer’s disease imaging biomarkers

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 29, 2023

Abstract Whether a relationship exists between cerebrovascular disease and Alzheimer’s has been source of controversy. Evaluation the temporal progression imaging biomarkers these processes may inform mechanistic associations. We investigate trajectories (white matter hyperintensity, WMH, fractional anisotropy, FA) (amyloid tau PET) in 2406 Mayo Clinic Study Aging Disease Research Center participants using accelerated failure time models. The model assumes common pattern for each biomarker that is shifted earlier or later individual represented by per participant age adjustment. An individual’s amyloid PET adjustments show very weak association with WMH FA (R = −0.07 to 0.07); early/late timing explains <1% variation Earlier onset associated 0.57, R 2 32%). These findings support strong aggregation, but not PET.

Язык: Английский

---

Associations of Serum Insulin and Related Measures With Neuropathology and Cognition in Older Persons With and Without Diabetes

Annals of Neurology, Год журнала: 2024, Номер 95(4), С. 665 - 676

Опубликована: Фев. 20, 2024

To examine associations of serum insulin and related measures with neuropathology cognition in older persons.

Язык: Английский

---

Frequency and Underlying Pathology of Pure Vascular Cognitive Impairment

JAMA Neurology, Год журнала: 2022, Номер 79(12), С. 1277 - 1277

Опубликована: Окт. 24, 2022

It is not clear how common pure vascular cognitive impairment (VCI) in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies.To identify participants without AD and pathologies determine extent to which cerebrovascular were associated with impairment.This clinical pathological study included from 2 ongoing community-based cohorts that began enrollment 1994 1997. Prior death, observed for a mean (SD) 8.4 (5.3) years annual assessments. From 2096 who died, 1799 (85.8%) underwent autopsy 1767 had complete postmortem examination data at time analyses. To pathologies, we categorized them 3 subgroups. A subgroup was composed significant levels brain pathologies. mixed rest participants. Data analyzed May 2021 July 2022.Brain pathology indices obtained by assessments.The primary outcome defined presence mild or dementia. The secondary cognition assessed 19 neuropsychological tests.Of participants, 1189 (67.3%) women, age death 89.4 (6.6) years. In (n = 369), present 156 (42.3%) (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P < .001; arteriolosclerosis basal ganglia: OR, 1.35; 1.04-1.76; .03) but an indication VCI. mixed-effects models including all only macroinfarcts faster decline rate (estimate, -0.019; SE, 0.005; .001) subgroup. Further analyses identified frontal white matter be when cortical subcortical regions examined single model.In this study, VCI rare. Macroinfarcts, specifically matter, main

Язык: Английский

---