Cerebral β-Amyloid Angiopathy Is Associated with Earlier Dementia Onset in Alzheimer's Disease

Vidoni, Eric D.; Morris, Jill K.; Newell, Kathy L.; Alqahtani, Abdulfattah S.; Burns, Nicole; Burns, Jeffrey M.; Billinger, Sandra A.

doi:10.1159/000441919

Cited by 23 publications

(11 citation statements)

References 19 publications

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“…The Aβ deposited in the vascular walls triggers several ischemia-induced pathogenic molecular pathways, such as oxidative stress, inflammation and increased blood-brain barrier (BBB) permeability, leading to further hemorrhagic complications (Ghiso et al, 2010). A study based on parametric analysis of neuropathological data from the National Alzheimer's Coordinating Centers' dataset suggested that CAA was facilitating early stage dementia and the transition to moderate dementia (Vidoni et al, 2016). In severe CAA cases, Aβ deposition is usually followed by microaneurysms in cerebral blood vessels (Vonsattel et al, 1991), a vascular pathology shared by retinal vascular diseases such as diabetic retinopathy, which can be easily examined by fundoscopy (Friberg et al, 1987;Hellstedt et al, 1996).…”

Section: Retinal Vascular Pathology In Alzheimer's Diseasementioning

confidence: 99%

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

et al. 2020

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The neurosensory retina emerges as a prominent site of Alzheimer's disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that can, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal vascular amyloidosis and predicted cerebral amyloid angiopathy scores. These studies brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, is currently under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient-and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer's retinopathy.

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Section: Retinal Vascular Pathology In Alzheimer's Diseasementioning

confidence: 99%

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

et al. 2020

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“…Diagnosis of cognitively normal pre-clinical AD followed the recommendations from NIA and the Alzheimer's Association workgroup (Sperling et al, 2011). The protocol for determination of amyloid elevation is detailed elsewhere (Vidoni et al, 2016). The average time between administration of PET scan and EEG assessment was 1090 (479) days.…”

Section: Participantsmentioning

confidence: 99%

Reliability of P3 Event-Related Potential During Working Memory Across the Spectrum of Cognitive Aging

Devos

Burns

Liao

et al. 2020

Front. Aging Neurosci.

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Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals with a vast range of cognitive ability has not been established. In this test-retest reliability study, 39 older individuals (age 74.10 (5.4) years; 23 (59%) women; 15 non β-amyloid elevated, 16 β-amyloid elevated, 8 cognitively impaired) with scores on the Montreal Cognitive Assessment (MOCA) ranging between 3 and 30 completed a working memory (n-back) test with three levels of difficulty at baseline and 2-week follow-up. The main aim was to evaluate stability of the ERP on grand averaged task effects for both visits in the total sample (n = 39). Secondary aims were to evaluate the effect of age, group (non β-amyloid elevated; β-amyloid elevated, cognitively impaired), cognitive status (MOCA), and task difficulty on ERP reliability. P3 peak amplitude and latency were measured in predetermined channels. P3 peak amplitude at Fz, our main outcome variable, showed excellent reliability in 0back (intraclass correlation coefficient (ICC), 95% confidence interval = 0.82 (0.67-0.90) and 1-back (ICC = 0.87 (0.76-0.93), however, only fair reliability in 2-back (ICC = 0.53 (0.09-0.75). Reliability of P3 peak latencies was substantially lower, with ICCs ranging between 0.17 for 2-back and 0.54 for 0-back. Generalized linear mixed models showed no confounding effect of age, group, or task difficulty on stability of P3 amplitude and latency of Fz. By contrast, MOCA scores tended to negatively correlate with P3 amplitude of Fz (p = 0.07). We conclude that P3 peak amplitude, and to lesser extent P3 peak latency, provide a stable measure of electrophysiological processes in older individuals.

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“…Severe CAA can impair blood flow and produce ischemic lesions or small infarcts, while severe CAA can lead to lobar hemorrhages typically affecting the frontal and occipital lobes [18]. The preponderance of CAA in AD and its association with an earlier age of onset support its role on the disease process, independently contributing to clinical presentations of AD [46, 49, 50]. Several methods have been proposed to score severity of CAA burden, and imaging techniques are being developed to differentiate CAA from plaque amyloid [46].…”

Section: Introductionmentioning

confidence: 99%

The neuropathological diagnosis of Alzheimer’s disease

DeTure

Dickson

2019

Mol Neurodegeneration

2,082

1,322

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Alzheimer’s disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The cardinal pathological features of the disease have been known for more than one hundred years, and today the presence of these amyloid plaques and neurofibrillary tangles are still required for a pathological diagnosis. Alzheimer’s disease is the most common cause of dementia globally. There remain no effective treatment options for the great majority of patients, and the primary causes of the disease are unknown except in a small number of familial cases driven by genetic mutations. Confounding efforts to develop effective diagnostic tools and disease-modifying therapies is the realization that Alzheimer’s disease is a mixed proteinopathy (amyloid and tau) frequently associated with other age-related processes such as cerebrovascular disease and Lewy body disease. Defining the relationships between and interdependence of various co-pathologies remains an active area of investigation. This review outlines etiologically-linked pathologic features of Alzheimer’s disease, as well as those that are inevitable findings of uncertain significance, such as granulovacuolar degeneration and Hirano bodies. Other disease processes that are frequent, but not inevitable, are also discussed, including pathologic processes that can clinically mimic Alzheimer’s disease. These include cerebrovascular disease, Lewy body disease, TDP-43 proteinopathies and argyrophilic grain disease. The purpose of this review is to provide an overview of Alzheimer’s disease pathology, its defining pathologic substrates and the related pathologies that can affect diagnosis and treatment. Electronic supplementary material The online version of this article (10.1186/s13024-019-0333-5) contains supplementary material, which is available to authorized users.

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Cerebral β-Amyloid Angiopathy Is Associated with Earlier Dementia Onset in Alzheimer's Disease

Cited by 23 publications

References 19 publications

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

Reliability of P3 Event-Related Potential During Working Memory Across the Spectrum of Cognitive Aging

The neuropathological diagnosis of Alzheimer’s disease

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