Faculty Bibliography

Background: The association of blood pressure (BP) and dementia in the elderly is debated. Whereas hypertension in mid-life appears to increase the risk of Alzheimer's dementia (AD); lower BP in the elderly is associated with a greater risk of cognitive decline. White matter lesions (WML) are the result of impaired cerebral blood flow, possibly due to insufficient perfusion pressure. The hippocampus, an early site of AD pathology, is also among the brain structures most sensitive to hypoperfusion. We tested the hypothesis that elderly normotensive subjects with WML represent a group suffering from subclinical cerebral hypoperfusion, which increases their risk for AD. We examined 24-hour ambulatory blood pressure (ABP), hippocampal volume and memory in four groups of subjects: hypertensive (HTN+) and normotensive (HTN-) subjects with (WML+) and without (WML-) white matter changes. Methods: Sixty-six subjects (mean age 72.63 6 8.48, 62% female) underwent a thorough medical assessment, brain magnetic resonance imaging (MRI), 24 hour ABP monitoring, and memory testing. Fluid attenuated inversion recovery images were used to determine the WML using the Fazekas scale. Periventricular (PWML) and deep white matter lesions (DWML) were graded separately and summed to create the total load. High load (WML+) was defined as a total load >3. Brain volumes were obtained from T1- weighted MRI images using FreeSurfer. Memory tests were converted to age, education and gender adjusted standardized scores. HTN was determined based on antihypertensive medication use and the results of 24 h APBM. Results: Groups differed in age, but not in education or gender (Table 1). HTNWML+ group had the lowest mean systolic BP (F=43.0, p<.001), and the lowest mean awake systolic BP (F=45.0, p<.001) (Table 1). Post hoc contrast analyses showed that hippocampal volumes, but not whole brain volumes, decreased linearly from HTN-WML-, through HTN+WML- and HTN+WML+, to HTN-WML+ group (p=.006) (for the entire model F=2.7, p=.049) (Figure 1). Memory scores showed a similar trend (p=.10) (for the entire model F=1.9, p=.10) (Figure 2). Conclusions: Normotensive elderly with WML have lower BP, lower hippocampal volumes and poorer memory overall. This constellation of clinical and imaging characteristics may increase their risk of developing AD. (Figure Presented)

Background: Metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease that deserves significant attention. While there is a growing recognition of the link between MetS and cognition, little is known about how MetS relates to cortical amyloid deposition. The detection of vascular risk is commonly followed by an introduction of appropriate treatment aimed at risk modification. The treatment itself may affect accumulation of brain amyloid, but this issue is largely unknown. Our aim was to assess the relationships between MetS, antihypertensive and antilipid medications, and cortical amyloid binging of Pittsburgh compound B (PiB) in cognitively healthy adults and elderly. Methods: A crosssectional study of subjects (n=155) participating in studies of brain aging who underwent Positron Emission Tomography (PET) imaging with PiB. Sixty-seven percent were women, mean age of the entire group was 60.4+/-10.5 years, mean education 16.6+/-2.0 years. General linear models were used to compare groups. Predictors of cortical amyloid accumulation were tested with linear regression models. Tested predictors included MetS, visceral obesity, blood pressure, glucose, HDL and triglycerides levels, treatment with angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzymes inhibitor, statins, antidepressants, demographics, and ApoE 4 carrier status. Results: After accounting for age and the treatment with antidepressants, the use of ARBs (b=-.15, p=.048) and diuretics (b=-.28, p=.001) predicted less amyloid accumulation, while statins (b=.19, p=.015) were the related to more cortical amyloid deposition. Although MetS was not related to amyloid deposition, central obesity was associated with greater cortical amyloid in women irrespective of medication status. Conclusions: ARBs and diuretics were associated with less amyloid deposition. Prospective studies should confirm this benefit of antihypertensive drugs and establish whether such modifications translate into measurable clinical outcomes. Women may be particularly sensitive to detrimental effects of obesity on the aging brain. This must be taken into consideration while planning future interventions

OBJECTIVE: The purpose of this study was to investigate the additional value of whole-lesion histogram apparent diffusion coefficient (ADC) metrics, when combined with standard pathologic features, in prediction of biochemical recurrence (BCR) after radical prostatectomy for prostate cancer. MATERIALS AND METHODS: The study included 193 patients (mean age, 61 +/- 7 years) who underwent 3-T MRI with DWI (b values, 50 and 1000 s/mm(2)) before prostatectomy. Histogram metrics were derived from 3D volumes of interest encompassing the entire lesion on ADC maps. Pathologic features from radical prostatectomy and subsequent BCR were recorded for each patient. The Fisher exact test and Mann-Whitney test were used to compare ADC-based metrics and pathologic features between patients with and patients without BCR. Stepwise logistic regression analysis was used to construct multivariable models for prediction of BCR, which were assessed by ROC analysis. RESULTS: BCR occurred in 16.6% (32/193) of patients. Variables significantly associated with BCR included primary Gleason grade, Gleason score, extraprostatic extension, seminal vesicle invasion, positive surgical margin, preoperative prostate-specific antigen level, MRI tumor volume, mean whole-lesion ADC, entropy ADC, and mean ADC of the bottom 10th, 10-25th, and 25-50th percentiles (p