Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats.

Hypertension, including transient events, is a major risk factor for developing late-onset dementia and Alzheimer's disease (AD). Anti-hypertensive drugs facilitate restoration of normotension without amelioration of increased dementia risk suggesting that transient hypertensive insults cause irreversible damage. This study characterized the contribution of transient hypertension to sustained brain damage as a function of normal aging and AD. To model transient hypertension, we treated F344TgAD and non-transgenic littermate rats with L-NG-Nitroarginine methyl ester (L-NAME) for one month, ceased treatment and allowed for a month of normotensive recovery. We then examined the changes in the structure and function of the cerebrovasculature, integrity of white matter, and progression of AD pathology. As independent factors, both transient hypertension and AD compromised structural and functional integrity across the vascular bed, while combined effects of hypertension and AD yielded the largest deficits. Combined effects of transient hypertension and AD genotype resulted in loss of cortical myelin particularly in the cingulate cortex which is crucial for cognitive function. Increased cerebral amyloid angiopathy, a prominent pathology of AD, was detected after transient hypertension as were up- and down-regulation of proteins associated with cerebrovascular remodeling - osteopontin, ROCK1 and ROCK2, in F344TgAD rats even 30 days after restoration of normotension. In conclusion, transient hypertension caused permanent cerebrovasculature and brain parenchymal damage in both normal aging and AD. Our results corroborate human studies that have found close correlation between transient hypertension in midlife and white matter lesions later in life outlining vascular pathologies as pathological links to increased risk of dementia.

Prospective comparison of course of disability in antipsychotic-treated and untreated schizophrenia patients.

OBJECTIVE: To compare the course of disability in schizophrenia patients receiving antipsychotics and those remaining untreated in a rural community. METHOD: Of 215 schizophrenia patients identified in a rural south Indian community, 58% were not receiving antipsychotics. Trained raters assessed the disability in 190 of these at baseline and after 1 year. The course of disability in those who remained untreated was compared with that in those who received antipsychotics. RESULTS: Mean disability scores remained virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated (P < 0.001; group x occasion effect). The proportion of patients classified as 'disabled' declined significantly in the treated group (P < 0.01), but remained the same in the untreated group. CONCLUSION: Disability in untreated schizophrenia patients remains unchanged over time. Treatment with antipsychotics in the community results in a considerable reduction in disability.