Dysautonomia in Alzheimer's Disease

Abstract

<jats:p>Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.</jats:p>

The role of cardiovascular autonomic failure in the differential diagnosis of α-synucleinopathies

“…Compared to parkinsonism, there is only limited data available in cognitively impaired individuals, especially with regard to tauopathy-related dementia [34]. While it remains to be clarified whether τ-related neuropathological changes involving central autonomic relays may cause overt cardiovascular autonomic failure [67,68,70], an otherwise unexplained neurogenic OH with evidence of cardiac sympathetic denervation yields a high negative predictive value for tauopathy-related dementia and rather points to an α-synucleinopathy-related dementia [55,67,68,71]. PD with dementia and DLB are still separated by the one-year rule [19].…”

“…Overall, current data on cardiovascular autonomic failure in tauopathy-related cognitive impairment are scarce, provide contrasting results, and remain limited by a substantial heterogeneity [68]. The frequency of overt neurogenic OH in people with clinically ascertained tauopathies remained low in the reviewed studies and the role of age-related confounders, such as cardiovascular comorbidities, medications, mixed pathology, or aging itself, remains to be clarified [67,68,70].…”

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

“…Interestingly, the recently reported COVID-19-related autonomic dysfunction has been characterized in AD for three decades [ 7 ] and proposed to develop in the preclinical phase of the disease [ 78 ]. The most common symptoms of AD-associated dysautonomia are cardiac failure or infarction [ 79 ], blood pressure dysregulation [ 80 ], decreased baro-reflex function [ 81 ], bronchopneumonia [ 82 ], par-asympathetic drive hypofunction [ 83 ], altered pain perception and reactivity [ 84 ], and orthostatic hypo-tension [ 7 ]. In AD patients, lower cognitive performance (especially regarding memory) was related to significantly higher cardiac sympathetic and lower parasympathetic function, independently of age, sex, academic years, diabetes, hypertension, and cho-linesterase inhibitor use [ 85 ].…”

“…Interestingly, the recently reported COVID-19related autonomic dysfunction has been character-ized in AD for three decades [7] and proposed to develop in the preclinical phase of the disease [78]. The most common symptoms of AD-associated dysautonomia are cardiac failure or infarction [79], blood pressure dysregulation [80], decreased baroreflex function [81], bronchopneumonia [82], parasympathetic drive hypofunction [83], altered pain perception and reactivity [84], and orthostatic hypotension [7].…”

“…The recent epidemiological data thus suggest a link between aging and AD regarding fatal outcomes of COVID-19 [6]. Another possible link between aging, AD, and COVID19 concerns a common range of dysfunctions of the autonomic nervous system, or dysautonomia, along with an increased systemic inflammation tone [7,8]. The lethal outcomes of COVID-19 might be due to postinfection hypertension and hypoventilation, which is caused by nervous dysfunction of autonomic brainstem centers and reflexes.…”