Age-related impairment of neurovascular coupling responses: a dynamic vessel analysis (DVA)-based approach to measure decreased flicker light stimulus-induced retinal arteriolar dilation in healthy older adults.

Aging is a major risk factor for vascular cognitive impairment and dementia (VCID). Recent studies demonstrate that cerebromicrovascular dysfunction plays a causal role in the development of age-related cognitive impairment, in part via disruption of neurovascular coupling (NVC) responses. NVC (functional hyperemia) is responsible for adjusting cerebral blood flow to the increased energetic demands of activated neurons, and in preclinical animal models of aging, pharmacological restoration of NVC is associated with improved cognitive performance. To translate these findings, there is an increasing need to develop novel and sensitive tools to assess cerebromicrovascular function and NVC to assess risk for VCID and evaluate treatment efficacy. Due to shared developmental origins, anatomical features, and physiology, assessment of retinal vessel function may serve as an important surrogate outcome measure to study neurovascular dysfunction. The present study was designed to compare NVC responses in young (< 45 years of age; n = 18) and aged (> 65 years of age; n = 11) healthy human subjects by assessing flicker light-induced changes in the diameter of retinal arterioles using a dynamic vessel analyzer (DVA)-based approach. We found that NVC responses in retinal arterioles were significantly decreased in older adults as compared with younger subjects. We propose that the DVA-based approach can be used to assess NVC, as a surrogate cerebromicrovascular outcome measure, to evaluate the effects of therapeutic interventions in older individuals.

Age-related decline in peripheral vascular health predicts cognitive impairment.

Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young (< 45 years old) and aged (> 65 years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 ± 0.7% vs. 8.3 ± 0.6% in young, p = 0.0061), increased arterial stiffness (AIx 29.3 ± 1.8% vs 4.5 ± 2.6% in young, p < 0.0001), and microvascular dysfunction (2.8 ± 0.2 vs 3.4 ± 0.1-fold change of perfusion in young, p = 0.032). VHI showed a significant negative correlation with age (r = - 0.54, p < 0.0001) and CII significantly correlated with age (r = 0.79, p < 0.0001). VHI significantly correlated with the CII (r = - 0.46, p = 0.0003). A decline in peripheral vascular health may reflect generalized vascular dysfunction and predict cognitive impairment in older adults.

Dealing with mild cognitive impairment: help for patients and caregivers.

Mild cognitive impairment (MCI) is a unique entity in the spectrum of syndromes of cognitive loss. Many patients referred for evaluation of memory loss come with an assumption that they already have dementia. When patients are diagnosed with MCI, they and their caregivers have to deal with the challenge of uncertainties. Patient and family education must stress the uncertainty of whether the deficits will progress. This article aims to guide the clinician who has reached a diagnosis of MCI and is working with the patient and family on coping with the uncertainties of MCI.

Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow-up, 4.9 years) by randomized groups: chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) in a randomized double-blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group-a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.