***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Hypertension is associated with mild decrements in cognition . In addition , regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults , who , compared with normotensive subjects , manifest greater correlation in blood flow response across task-related brain regions . Here , we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class . Treatment with lisinopril , an angiotensin-converting enzyme blocker , known to enhance vasodilative responsivity , was compared with treatment with atenolol , a & bgr;-blocker .  Untreated hypertensive volunteers ( n=28 ) were r and omly assigned and treated for 1 year . Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide , a vasodilator , were assessed pretreatment and posttreatment . Peripheral brachial artery dilation during reactive hyperemia was also measured . Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection . Brachial artery flow-mediated dilation increased with treatment . No differences between medications were observed . In brain regions active in memory processing , however , regional cerebral blood flow responses were more highly correlated after treatment . Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension . This greater correlation among active brain regions , which is present as well in untreated hypertensive relative to normotensive volunteers , may represent compensation in the face of less region-specific responsivity in individuals with hypertension Background —  High blood pressure  (  BP ) is a risk factor for cerebrovascular disease , including stroke . Little is known about the importance of BP on the progression of microvascular disease of the brain , which has been associated with functional decline in mobility and cognition in older people . Methods and Results — This was a prospect i ve cohort of subjects 75 to 89 years of age to determine relations among vascular risk factors , white matter hyperintensity volume , and functional status . Ninety-nine subjects were enrolled through the use of a balanced 3 × 3 matrix stratified by age and mobility performance , and 72 subjects completed all sets of baseline and follow-up studies at 2 years . Subjects were excluded if there were medications or systemic or neurological diseases that could compromise mobility .  Ambulatory and clinic BP monitoring , magnetic resonance imaging , gait studies , and neuropsychological testing  were performed at baseline and after 24 months . Brain classification into normal white matter and T2-hyperintense white matter hyperintensity volume was performed with semiautomated segmentation . Quantitative measures of mobility and cognitive function were obtained longitudinally . Increased ambulatory systolic BP , but not clinic systolic BP , from baseline to 24 month follow-up was associated with increased white matter hyperintensity volume over that same period , as well as measures of executive function/processing speed . Similar associations were observed for 24-hour BP , awake BP , and sleep BP but not for the surge between the sleep and awake time at the 24-month time point . Conclusions — These data demonstrate for the first time the importance of 24-hour systolic BP in the progression of brain white matter hyperintensity volume burden associated with impairment of cognitive function in older people . The 24-hour systolic BP may be a potential target for intervention in the elderly to reduce vascular disease of the brain and impairment of function BACKGROUND AND PURPOSE Cross-sectional studies show that cerebrovascular risk factors are associated with increased brain atrophy , accumulation of abnormal cerebral white matter signals , and clinical ly silent stroke . We extend these findings by examining the relationship between midlife cerebrovascular risk factors and later-life differences in brain atrophy , amount of abnormal white matter , and stroke on MRI . METHODS Subjects were the 414 surviving members of the prospect i ve National Heart , Lung , and Blood Institute Twin Study , who have been examined on 4 separate occasions , spanning the 25 years between 1969 - 1973 and 1995 - 1997 . Quantitative measures of brain volume , volume of abnormal white matter signal ( WMHI ) , and volume of stroke , when present , were obtained from those participating in the fourth examination . RESULTS The mean+/-SD age of the subjects was 47.2+/-3.0 years at initial examination and 72 . 5+/-2.9 years at final examination .  Average blood pressure ( BP ) levels were normal , although 32 % of the subjects had received or were currently taking antihypertensive medications . As a group , 31 % had symptomatic cardiovascular disease , 11 % had symptomatic cerebrovascular disease , and 8 % had symptomatic peripheral vascular disease . Both systolic and diastolic BP levels at initial examination were inversely related to brain volume and positively related to WMHI volume . Multiple regression analysis identified BP-related measures and vascular risk factors as significant predictors of brain and WMHI volumes . In addition , the magnitude of orthostatic BP change was significantly associated with WMHI volume . Subjects with extensive amounts of WMHI had significantly higher systolic BP at the final examination and a higher prevalence of symptomatic cardiovascular and cerebrovascular disease , without significant differences in the prevalence of hypertension treatment . CONCLUSIONS Midlife BP measures are significantly associated with later-life brain and WMHI volumes and the prevalence of symptomatic vascular disease . Since WMHI share cerebrovascular risk factors and extensive WMHI are associated with symptomatic vascular disease , extensive WMHI may be a sub clinical expression of cerebrovascular disease . Careful treatment of midlife BP elevations may diminish these later-life brain changes Diabetic patients are at increased risk for stroke , but little is known about the presence of other brain lesions . We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65 - 75 years who were r and omly selected from eight European population registries or defined working population s. All scans were central ly read for brain abnormalities , including infa rcts , white matter lesions , and atrophy . We used a three-point scale to rate periventricular white matter lesions , and the volume of subcortical lesions was calculated according to their number and size . Subjective grading of cortical atrophy by lobe and summation of the lobar grade s result ed in a total cortical atrophy score . The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy . After adjustment for possible confounders , diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy . There was a strong interaction of diabetes and hypertension , such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants . Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to underst and the mechanisms underlying these associations Nicotine , the primary addictive component of tobacco , affects the mammalian brain . Smokers ' brains have smaller cortical grey matter volumes and /or lower densities compared with non‐smokers ' . Differences in subcortical structures like the striatum are however , less clear . A high concentration of nicotinic receptors makes the striatum a potential target for nicotine . In addition , striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction . The aim of this study was to explore the relationship between striatal nuclei ( cau date , putamen and nucleus accumbens area ) volumes and lifetime smoking in a large community‐based sample of ‘ young – old ’ individuals . Brain volumes were measured using a semi‐automated method in 315 participants aged 64–70 years who were selected from a larger r and omly sample d cohort and who consented to a magnetic resonance imaging scan . Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age , sex , intracranial and total brain volumes and general physical and mental health measures . Greater lifetime use of cigarettes ( measured in pack‐years ) was associated with smaller left nucleus accumbens area volume ( P = 0.018 ) and larger left putamen volume ( P = 0.025 ) . Greater putaminal volume was also associated with a lower age at smoking initiation ( P = 0.004 ) . In this generally healthy cohort , lifetime use of cigarettes is significantly associated with striatal volume measures . These changes could indicate predisposing factors for nicotine addiction , or an effect of chronic nicotine exposure or a combination of both In the present study , we examined the relationships between whole brain volume ( WBV ) , subcortical hyperintensities ( SH ) , indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease . A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination , neuroimaging , and cardiac assessment . Cognition was assessed with the Dementia Rating Scale-2 ( DRS ) . WBV and SH were quantified using a semi-automated thresholding program based on MRI . Correlational analyses revealed that WBV predicted performance on the overall DRS score , the attention subscale and the initiation/perseveration scale . SH were significantly associated with performance on the attention subscale , and the initiation/perseveration subscale . Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale , whereas WBV accounted for most of the variance in the attention scale . The only cardiac structural or functional variable related to the neurological indices was aortic diameter , which was strongly related to both neuroimaging variables , as well as performances on the DRS attention and initiation/perseveration subscales . Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status Untreated hypertension negatively affects brain anatomy and cognitive functions , but the effects of medically treated hypertension are unclear . The authors compared 40 middle-age and older adults diagnosed with essential hypertension to demographically matched normotensive peers . Volumes of 7 brain regions and deep and periventricular white-matter hyperintensities ( WMH ) were measured on magnetic resonance imaging scans . Performance in 4 cognitive domains ( perseveration , working memory , fluid reasoning , and vocabulary knowledge ) was evaluated . Persons with hypertension had smaller prefrontal cortex and underlying white matter volumes and increased frontal WMH . No group differences were found in other examined brain regions . Among examined cognitive variables , hypertensive patients committed significantly more perseverative errors . Thus , even controlled hypertension may be associated with deficits in brain structure and cognition , warranting further study Existing work demonstrates that obesity is independently associated with cognitive dysfunction and macrostructural brain changes ; however , little is known about the association between obesity and white matter ( WM ) integrity . We explore this relationship in a large cohort of otherwise healthy subjects . The present study classified 103 adult participants from the Brain Re source International Data base between 21 and 86 years of age without history of neurological , medical , or psychiatric illness according to BMI ( normal weight , overweight , obese ) and subjected them to diffusion tensor imaging ( DTI ) .  Result ing fractional anisotropy ( FA ) indexes for the corpus callosum and fornix were examined in relation to BMI and age in a multiple regression framework . Results indicated that increasing BMI was independently associated with lower FA in the genu , splenium , and fornix , and a BMI × age interaction emerged for FA in the splenium and body of the corpus callosum . When categorized , obese persons demonstrated lower FA than normal and overweight persons for all WM indexes , but no FA differences emerged between overweight and normal persons . Results indicate both a direct association between obesity and reduced WM tract integrity and an interaction between obesity and aging processes on certain WM tracts in otherwise healthy adults . While such findings suggest a possible role for adiposity in WM dysfunction and associated cognitive deficits , prospect i ve studies are needed to clarify the nature of these relationships and eluci date underlying mechanisms 
    Output:
    
The 77 studies included in this review demonstrate that in persons without symptomatic cardiovascular , cerebrovascular , or peripheral vascular disease , the vascular risk factors of hypertension , diabetes mellitus , obesity , hyperlipidemia , and smoking are all independently associated with brain imaging changes before the clinical manifestation of cardiovascular or cerebrovascular disease .
We conclude that the identification of brain changes associated with vascular risk factors , before the manifestation of clinical ly significant cerebrovascular damage , presents a window of opportunity wherein adequate treatment of these modifiable vascular risk factors may prevent the development of irreversible deleterious brain changes and potentially alter patients ' clinical course