Journal of Alzheimer's disease : JAD
-
Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. ⋯ This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.
-
Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. ⋯ Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.
-
Several epidemiological studies have found an association between low educational level (or low cognitively demanding occupations) and dementia. Although other studies have not found evidence to support such an association, there has been a general trend toward a "use it or lose it" concept which attempts to promote a neuroprotective role of intellectual activity against the development of dementia. Formation of amyloid-beta peptide (Abeta) in the brain plays a key role in the development of Alzheimer's disease whilst glutamate has been implicated in the pathophysiology of a number of neurological disorders including Alzheimer's disease and vascular dementia. ⋯ Long-term potentiation (LTP, a biological correlate of learning and memory) increases the sensitivity of hippocampal neurons to synaptically released glutamate whilst decreasing responses of neurons to bath applied glutamate receptor agonists and to hypoxia/ischemia in vitro. The effects of LTP are likely to involve changes in intracellular Ca2+ concentration. Based on these findings we are proposing that the LTP-induced neuroprotection in vitro may help explain the epidemiological evidence of a possible neuroprotective role of high intellectual activity against dementia.