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Autonomic dysfunction is very common in patients with dementia, and its presence might also help in differential diagnosis among dementia subtypes. Various central nervous system structures affected in Alzheimer's disease (AD) are also implicated in the central autonomic nervous system (ANS) regulation. For example, deficits in central cholinergic function in AD could likely lead to autonomic dysfunction. We recently developed a simple, readily applicable evaluation for monitoring ANS disturbances in response to traumatic brain injury (TBI). This ability to monitor TBI allows for the possible detection and targeted prevention of long-term, detrimental brain responses caused by TBI that lead to neurodegenerative diseases such as AD. We randomly selected and extracted de-identified medical record information from subjects who have been assessed using the ANS evaluation protocol. Using machine learning strategies in the analysis of information from individual as well as a combination of ANS evaluation protocol components, we identified a novel prediction model that is effective in correctly segregating between cases with or without a documented history of TBI exposure. Results from our study support the hypothesis that trauma-induced ANS dysfunctions may contribute to clinical TBI features. Because autonomic dysfunction is very common in AD patients it is possible that TBI may also contribute to AD and/or other forms of dementia through these novel mechanisms. This study provides a novel prediction model to physiologically assess the likelihood of subjects with prior history of TBI to develop clinical TBI complications, such as AD. [ABSTRACT FROM AUTHOR]

Recent studies suggest that certain cardiovascular antihypertensive agents decrease the incidence of Alzheimer's disease. Based on this evidence and the fact that Aβ aggregation into high-molecular-weight-soluble oligomeric Aβ species is known to directly induce cognitive impairment, we tested the possibility that certain antihypertensive compounds may affect the progression of Alzheimer's disease, at least in part by influencing the formation of Aβ oligomers. High throughput screening of 55 commercially available antihypertensive drugs identified four compounds that significantly reduced Aβ_{1-42} oligomerization in a dose dependent manner. These four compounds, furosemide (diuretic), nitrendipine (calcium channel blocker), candesartan cilextil (angiotensin II receptor antagonist) and diazoxide (vasodilator) showed no detectable Aβ lowering activities in primary neuron cultures generated from Tg2576 mouse embryos. However, furosemide, nitrendipine and candesartan cilextil prevented oligomerization of both Aβ_{1-40} and Aβ_{1-42} in vitro. Furosemide also dissociated pre-aggregated Aβ_{1-42} oligomers. Furthermore, short term furosemide treatment resulted in decreased amount of Aβ oligomers in the brain of Tg2576 mice. Our studies suggest that certain antihypertensive compounds may prevent AD-type neuropathology through inhibition of Aβ oligomer formation. [ABSTRACT FROM AUTHOR]

Recent studies suggest that certain cardiovascular antihypertensive agents decrease the incidence of Alzheimer's disease. Based on this evidence and the fact that Abeta aggregation into high-molecular-weight-soluble oligomeric Abeta species is known to directly induce cognitive impairment, we tested the possibility that certain antihypertensive compounds may affect the progression of Alzheimer's disease, at least in part by influencing the formation of Abeta oligomers. High throughput screening of 55 commercially available antihypertensive drugs identified four compounds that significantly reduced Abeta(1-42) oligomerization in a dose dependent manner. These four compounds, furosemide (diuretic), nitrendipine (calcium channel blocker), candesartan cilextil (angiotensin II receptor antagonist) and diazoxide (vasodilator) showed no detectable Abeta lowering activities in primary neuron cultures generated from Tg2576 mouse embryos. However, furosemide, nitrendipine and candesartan cilextil prevented oligomerization of both Abeta(1-40) and Abeta(1-42) in vitro. Furosemide also dissociated pre-aggregated Abeta(1-42) oligomers. Furthermore, short term furosemide treatment resulted in decreased amount of Abeta oligomers in the brain of Tg2576 mice. Our studies suggest that certain antihypertensive compounds may prevent AD-type neuropathology through inhibition of Abeta oligomer formation.