Hypertension has been linked with peripheral and central reductions in vascular density, and with devastating effects on brain function. However, the underlying mechanisms in the relationship between blood pressure and cognitive impairment have yet to be fully elucidated. Here, we review compelling evidence from two lines of inquiry: one that links microvascular rarefaction with insulin-like growth factor 1 (IGF-1) deficiencies, and another which posits that vascular dysfunction precedes hypertension. Based on the findings from experimental and clinical studies, we propose that these lines of evidence converge, and suggest that agerelated declines in IGF-1 concentrations precede microvascular rarefaction, initiate an increase in vascular resistance, and therefore are causally linked to onset of hypertension. Physical exercise provides a relevant model for supporting our premise, given the wellestablished effects of exercise in attenuating vascular dysfunction, hypertension, IGF-1 deficiency, and cognitive decline. We highlight here the role of exerciseinduced increases in blood flow in improving vascular integrity and enhancing angiogenesis via the actions of IGF-1, resulting in reversal of rarefaction and hypertension, and enhancement of cerebral blood flow and cognition.

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The ability to non-invasively predict outcomes and monitor treatment response in primary central nervous system lymphoma (PCNSL) is important as treatment regimens are constantly being trialed. The aim of this study was to assess the validity of using apparent diffusion coefficient (ADC) histogram values to predict Ki-67 expression, a tumor proliferation marker, and patient outcomes in PCNSL in both immunocompetent patients and patients living with HIV (PLWH). Qualitative PCNSL magnetic resonance imaging (MRI) characteristics from 93 patients (23 PLWH and 70 immunocompetent) were analyzed, and whole tumor segmentation was performed on the ADC maps. Quantitative histogram analyses of the segmentations were calculated. These measures were compared to PCNSL Ki-67 expression. Progression-free survival (PFS) and overall survival (OS) were analyzed via comparison to the International Primary Central Nervous System Lymphoma Collaboration Group Response Criteria. Associations between ADC measures and clinical outcomes were assessed using univariate and multivariate Cox proportional hazards models. Normalized ADC (nADC)Min, nADCMean, nADC1, nADC5, and nADC15 values were significantly associated with a poorer OS. nADCMax, nADCMean, nADC5, nADC15, nADC75, nADC95, nADC99 inversely correlated with Ki-67 expression. OS was also significantly associated with lesion hemorrhage. PFS was not significantly associated with ADC values but with lesion hemorrhage. ADC histogram values and related parameters can predict the degree of tumor proliferation and patient outcomes for primary central nervous system lymphoma patients and in both immunocompetent patients and patients living with HIV.

Currently less than half of the estimated number of people with dementia in England receive a formal diagnosis of dementia or have contact with specialist dementia services. Case finding focused on high risk groups may be an effective way to identify the undiagnosed. This joint Surrey Downs Clinical Commissioning Group and Surrey and Borders NHS Foundation Trust quality improvement project aimed to increase the rate of dementia diagnosis across Surrey Downs using specialist link nurses (SLNs).Thirty three GP surgeries covering the entire Surrey Downs area took part in the project. Individuals at high risk of developing dementia were identified from GP electronic disease registers, and were offered screening at their GP practices by SLNs, using a combination of mini cognitive test (Mini-Cog) and functional assessment questionnaire (FAQ). Suitable individuals who screened positive were seen by their GP and where appropriate referred to secondary care services for further evaluation.Based on the presence of risk factors, 6657 (11.9%) people were identified from a total population of 55 845 over 65s, and 1980 (29.7%) completed the screening assessment. Three hundred and fifty eight (18.1%) individuals screened positive and were referred to their GP, who referred 205 (57.2%) of them to the memory services for further assessment. Of those referred, 164 (80%) had a comprehensive specialist assessment. Forty one (20%) declined further assessment, and their GPs were informed.The mean age of the cohort who completed the comprehensive assessment was 82.3 years (SD=4.26), and were predominantly white and male. Fifty four (32.9%) had mild cognitive disorder (MCD), and 101 (61.6%) patients were diagnosed with dementia. The most common dementia was mixed type (43; 42.6%), followed by Alzheimer's dementia (32; 31.7%). The most common risk factor among patients with cognitive impairment (MCD or dementia) was hypertension (69; 44.5 %), followed by ischemic heart disease (64, 41.3%).Nurse led case finding for cognitive impairment in a high risk population identifies people with dementia who are not yet formally diagnosed.The combined use of brief instruments to assess cognitive functioning and functional capabilities is helpful in identifying individuals with possible dementia. ProblemDementia is degenerative disorder with an increasing prevalence. that one third of people with dementia had waited longer than a year to go to their GP with their symptoms. The reasons for this are complex and may include an assumption that memory problems are normal in older age a fear of the diagnosis, a view that little can be done to help, and the perceived stigma of dementia. (7,8)