Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer's and Parkinson's Disease: A Comprehensive Review.

Abstract

SARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS). Emerging evidence suggests a potential link between SARS-CoV-2-induced neuroinflammation and the exacerbation or initiation of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review explores the mechanisms by which SARS-CoV-2 may contribute to neurodegenerative processes. We first discuss the pathways of viral entry into the CNS, including transneuronal and hematogenous routes, leading to blood-brain barrier (BBB) dysfunction. Neuroinflammation, mediated by the activation of microglia and astrocytes and the release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β, is highlighted as a critical factor exacerbating neuronal damage. Oxidative stress and vascular damage are further examined as complementary mechanisms promoting neurodegeneration. In addition, we review how SARS-CoV-2 infection influences proteinopathies by accelerating the aggregation of pathological proteins like alpha-synuclein, tau, and TDP-43, contributing to disease progression in PD, AD, and related disorders. Clinical studies reporting cognitive and motor dysfunctions in post-COVID-19 patients with pre-existing neurodegenerative diseases are also summarized. Finally, this review identifies knowledge gaps and emphasizes the need for further research to clarify the long-term neurological consequences of SARS-CoV-2 infection. Understanding these mechanisms is critical for developing targeted therapeutic strategies to mitigate the risk of neurodegeneration in vulnerable populations.