Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.

BACKGROUND: Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. METHODS: Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation. RESULTS: Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (ß=-0.43; P=0.04) and higher CVR in the whole brain (ß=0.11; P=0.02), frontal lobes (ß=0.12; P<0.05), temporal lobes (ß=0.11; P=0.02), and occipital lobes (ß=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (ß=-1.16; P=0.047), lower temporal lobe CBF (ß=-1.81; P=0.004), and higher temporal lobe CVR (ß=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (ß=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (ß=-1.20; P=0.02). CONCLUSIONS: Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.

Increased Incidence of Resistant Hypertension in Patients With Systemic Lupus Erythematosus: A Retrospective Cohort Study.

OBJECTIVE: To compare the risk of resistant hypertension (RHTN) in patients with systemic lupus erythematosus (SLE) and in controls without SLE, and to define factors associated with RHTN in patients with SLE. METHODS: We studied 1,044 patients with SLE and 5,241 control subjects using de-identified electronic health records from a tertiary care center. SLE was defined as ≥4 International Classification of Diseases, Ninth Revision codes for SLE and antinuclear antibody titer ≥1:160. RHTN was defined as uncontrolled blood pressure on 3 antihypertensive medications or requiring 4 or more antihypertensives to attain control. First, we compared the risk of RHTN between groups. Second, we examined the association between RHTN and all-cause mortality in patients with SLE. RESULTS: RHTN was nearly twice as prevalent in patients with SLE compared to control subjects (10.2% and 5.3%, respectively), with an incidence rate of 10.2 versus 6.1 cases per 1,000 person-years of observation (hazard ratio [HR] 1.72 [95% confidence interval 1.28-2.30]; P < 0.001, adjusted for age, sex, race, baseline end-stage renal disease [ESRD], creatinine, and calendar year). In patients with SLE, we found associations between RHTN and black race, lower renal function, hypercholesterolemia, and increased inflammatory markers. RHTN was associated with a significantly higher mortality risk (HR 2.91, P = 0.0005) after adjustment for age, sex, race, calendar year, creatinine, baseline ESRD, and number of visits. CONCLUSION: Patients with SLE have a higher risk of RHTN compared to frequency-matched controls, independent of multiple covariates. RHTN is an important comorbidity for clinicians to recognize in SLE, because it is associated with a higher risk of mortality.

Validity and Normative Data for the Biber Figure Learning Test: A Visual Supraspan Memory Measure.

The Biber Figure Learning Test (BFLT), a visuospatial serial figure learning test, was evaluated for biological correlates and psychometric properties, and normative data were generated. Nondemented individuals (n = 332, 73 ± 7, 41% female) from the Vanderbilt Memory & Aging Project completed a comprehensive neuropsychological protocol. Adjusted regression models related BFLT indices to structural brain magnetic resonance imaging and cerebrospinal fluid (CSF) markers of brain health. Regression-based normative data were generated. Lower BFLT performances (Total Learning, Delayed Recall, Recognition) related to smaller medial temporal lobe volumes and higher CSF tau concentrations but not CSF amyloid. BFLT indices were most strongly correlated with other measures of verbal and nonverbal memory and visuospatial skills. The BFLT provides a comprehensive assessment of all aspects of visuospatial learning and memory and is sensitive to biomarkers of unhealthy brain aging. Enhanced normative data enriches the clinical utility of this visual serial figure learning test for use with older adults.

Frailty Is Related to Subjective Cognitive Decline in Older Women without Dementia.

OBJECTIVES: Physical frailty (or loss of physiologic reserve) is associated with cognitive impairment and dementia. Subjective cognitive decline (SCD) may represent early pathologic changes of dementia. The association between these disease markers is unclear. DESIGN: Cross-sectional analysis. SETTING: Community-based participants from the Vanderbilt Memory & Aging Project. PARTICIPANTS: A total of 306 older adults with normal cognition (NC; n = 174) or mild cognitive impairment (MCI; n = 132). MEASUREMENTS: Frailty was measured using standard methods, and a composite frailty score was calculated. SCD was quantified using the Everyday Cognition Scale (ECog; total score and four domain scores). Objective cognition was assessed with the Montreal Cognitive Assessment (MoCA). Proportional odds models, stratified by sex, related the frailty composite to MoCA and total ECog score adjusting for age, education, body mass index, cognitive diagnosis, depressed mood, Framingham Stroke Risk Profile, apolipoprotein E (APOE ε4) carrier status, and height (for gait speed models). Secondary models related individual frailty components to SCD domains and explored associations in NC only. RESULTS: In women, frailty composite was related to MoCA (odds ratio [OR] = .56; P = .04), a finding attenuated in sensitivity analysis (OR = .59; P = .08). Frailty composite related to ECog total (OR = 2.27; P = .02), planning (OR = 2.63; P = .02), and organization scores (OR = 2.39; P = .03). Increasing gait speed related to lower ECog total (OR = .06; P = .003) and memory scores (OR = .03; P < .001). Grip strength related to lower ECog planning score (OR = .91; P = .04). In men, frailty was unrelated to objective and subjective cognition (P values >.07). Findings were consistent in the NC group. CONCLUSION: Frailty component and composite scores are related to SCD before the presence of overt dementia. Results suggest that this association is present before overt cognitive impairment. Results suggest a possible sex difference in the clinical manifestation of frailty, with primary associations noted in women. Further studies should investigate mechanisms linking early changes among frailty, SCD, and cognition. J Am Geriatr Soc, 1-9, 2019. J Am Geriatr Soc 67:1803-1811, 2019.

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

BACKGROUND/AIMS: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. RESULTS: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). CONCLUSION: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

APOE genotype modifies the association between central arterial stiffening and cognition in older adults.

Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (ß = -0.29, p = 0.01), executive function (ß = -0.44, p = 0.02), and episodic memory (ß = -3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.