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- Title
Early Stages of Pathogenesis in Memory Impairment during Normal Senescence and Alzheimer's Disease.
- Authors
Daulatzai, Mak Adam
- Abstract
Alzheimer's disease (AD) is a progressive, neurodegenerative brain disease of the elderly characterized by memory loss, cognition, and behavioral abnormalities. Aging is the single most important risk factor and there is no proven therapy. Aging invariably decreases sensory stimuli and impacts on the thalamocortical system and its connectivity to key brain regions. Memory dysfunction in senescence and early AD, a function of acetylcholine decrease, is accompanied with dysfunctional basal forebrain, parietal, prefrontal, and entorhinal cortices, and indeed hippocampus. Cholinergic neurotransmission protects neurons from amyloid-β production and its toxicity, while cholinergic depletion enhances both. Available data on sleep disordered breathing and genioglossus dysfunction throw light on possible pathogenetic events leading to hypoxemia. Memory disturbances in normal elderly and early AD patients are intimately related to hypoxia, a reduction in blood supply, and glucose hypometabolism in the hippocampus and a number of key brain areas. The current hypothesis on memory impairment in the elderly and Alzheimer's dementia, therefore, underscores age-related sensory losses, functional disconnection between strategic brain regions in conjunction with hypoxemia and hypometabolism. On the basis of available data, it is emphasized that (A) decreases in thalamocortical function decreases cholinergic activity and cerebral blood flow, while nocturnally, (B) repeated hypoxic events affect respiratory cholinergic mechanism and respiratory regulation. Consequently, the hypotrophy/atrophy of nucleus solitarius and nucleus ambiguus in pontomedullary junction affect hypoglossal nucleus, genioglossus function, upper airway patency, hypoxia, and cerebral oxygenation. These alterations may cause amyloid-β deposition extracellularly, and neurofibrillary cytopathology in cholinergic and other neurons intracellularly.
- Subjects
MEMORY disorders in old age; ALZHEIMER'S disease; AGING; ACETYLCHOLINE; DEMENTIA; HYPOXEMIA; PHARYNGEAL diseases; SLEEP apnea syndromes in old age
- Publication
Journal of Alzheimer's Disease, 2010, Vol 20, Issue 2, p355
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2010-1374