Premium
P1‐074: Long‐term hypertension contributes to the development of Alzheimer's disease
Author(s) -
Kadish Inga,
Bhullar Sukhkamal,
Groen Thomas
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.660
Subject(s) - cerebral blood flow , medicine , dementia , blood pressure , perfusion , cerebral perfusion pressure , stroke (engine) , cognitive decline , cardiology , reactive hyperemia , vascular dementia , risk factor , blood flow , disease , mechanical engineering , engineering
Background: Hypertension is a risk factor for stroke and vascular dementia, and the incidence of these diseases grows with increasing blood pressure. Recent studies have shown that hypertension is also a risk factor for Alzheimer’s disease (AD). Based on the literature and our preliminary studies, we hypothesize that sustained hypertension leads to a modified cerebral circulation such that sustained hypoperfusion or oligemia is impacted upon the aging process to induce increased pathology. Our preliminary studies indicate that Tg AD model mice exhibit decreased cerebral blood flow and blood volume when significant A depositions are present. These findings have led to the hypothesis that sustained hypertension will lead to decreased functional hyperemia in the brain, and that this cerebral hypoperfusion will contribute to the cognitive impairments of AD. Decreased blood flow will concurrently lead to increased amyloid deposition in the brain due to decreased clearance of A . The following studies are designed to test the hypothesis that long-term untreated hypertension will lead to perturbed vascular function, and increased cognitive dysfunction and pathology in AD model mice. Methods: Blood pressure, cerebral blood flow, cerebral functional hyperemia, cognitive performance and A deposition were quantitatively assessed in Tg AD model mice (APPswDI) at 12 months of age, after being implanted with an Alzet minipump with Angiotensin II at 10 months of age. At 12 months of age the animals (n 10/group) were tested in an array of behavioral tests to determine their cognitive status. Following the behavioral analysis, the animals were anesthetized, put in a stereotaxic frame, and laser Doppler flow measurements were performed, following these measurements a catheter were placed in the carotid artery for measuring direct BP. After this analysis, the animals are sacrificed for histopathological analysis. Results: Angiotensin II significantly increased blood pressure, which in turn decreased cortical blood flow and decreased functional hyperemia (“the neurovascular unit”). The hypertensive mice were cognitively impaired compared with nonhypertensive mice, and they showed significantly increased A load and cerebral amyloid angiopathy (CAA). Conclusions: Sustained midlife hypertension leads to decreased cerebral blood flow and cognitive deficits, thus early treatment of hypertension is important for preventing dementia.