Lower Prevalence of Asymptomatic Alzheimer's Disease Among Healthy African Americans.

OBJECTIVE: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals. METHODS: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions. RESULTS: Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aß42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). INTERPRETATION: Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024;96:463-475.

Characterization of African-American Super-Agers in the National Alzheimer's Coordinating Center cohort.

BACKGROUND: "Super-agers" are adults aged ≥80 with cognitive performance similar to persons two to three decades younger. Characteristics such as larger hippocampal volume, APOE-ε4 allele absence, higher educational attainment, female sex, and lifelong cognitive stimulation are associated with cognitive performance compatible with super-aging. These findings are based on predominantly white research samples. Limited data are available on African-American super-agers. To fill this gap, we explored potential factors associated with super-aging in older African-American adults. METHODS: Data from African-American participants aged ≥80 in the National Alzheimer's Coordinating Center (NACC) dataset were analyzed. Using global Clinical Dementia Rating (CDR) scores, participants were first categorized as impaired (score ≥0.5) or non-impaired/normal cognition (NC) (score = 0). From the NC group, super-agers were identified using NACC-data-driven cutoffs. Participants were considered super-agers if their memory performance was similar to persons aged 50-60 with NC, and their performance on other domains was within one standard deviation of the mean for persons aged ≥80. We examined group characteristics (NC, super-ager, impaired) using chi-square and ANOVA with pairwise comparisons. Multinomial logistic regression, adjusted for sex and education, evaluated correlates of super-ager group assignment. RESULTS: Data for 1285 African-American participants aged ≥80 were analyzed. We identified 24.7% (n = 316) NC, 4.8% (n = 61) super-agers, and 70.6% (n = 905) impaired. Super-agers were mostly female and more educated, had similar vascular comorbidities as the other groups, and had less sleep disorders, depression, and alcohol use. After adjusting for sex and education, super-ager group assignment was associated with less sleep disorders, less depression, and moderate alcohol use. CONCLUSIONS: Participants with controlled vascular risk, mental health, alcohol use, and sleep disorders tended to be in the super-ager group. These factors may be important focus areas in clinical practice to support cognitive resilience with aging in older African-American adults.

The Utility of Cerebrovascular Reactivity MRI in Brain Rehabilitation: A Mechanistic Perspective.

Cerebrovascular control and its integration with other physiological systems play a key role in the effective maintenance of homeostasis in brain functioning. Maintenance, restoration, and promotion of such a balance are one of the paramount goals of brain rehabilitation and intervention programs. Cerebrovascular reactivity (CVR), an index of cerebrovascular reserve, plays an important role in chemo-regulation of cerebral blood flow. Improved vascular reactivity and cerebral blood flow are important factors in brain rehabilitation to facilitate desired cognitive and functional outcomes. It is widely accepted that CVR is impaired in aging, hypertension, and cerebrovascular diseases and possibly in neurodegenerative syndromes. However, a multitude of physiological factors influence CVR, and thus a comprehensive understanding of underlying mechanisms are needed. We are currently underinformed on which rehabilitation method will improve CVR, and how this information can inform on a patient's prognosis and diagnosis. Implementation of targeted rehabilitation regimes would be the first step to elucidate whether such regimes can modulate CVR and in the process may assist in improving our understanding for the underlying vascular pathophysiology. As such, the high spatial resolution along with whole brain coverage offered by MRI has opened the door to exciting recent developments in CVR MRI. Yet, several challenges currently preclude its potential as an effective diagnostic and prognostic tool in treatment planning and guidance. Understanding these knowledge gaps will ultimately facilitate a deeper understanding for cerebrovascular physiology and its role in brain function and rehabilitation. Based on the lessons learned from our group's past and ongoing neurorehabilitation studies, we present a systematic review of physiological mechanisms that lead to impaired CVR in aging and disease, and how CVR imaging and its further development in the context of brain rehabilitation can add value to the clinical settings.

Perceived Stress is Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in African Americans with Mild Cognitive Impairment.

BACKGROUND: African Americans (AA) have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. OBJECTIVE: Establish biomarker evidence for the observed association between stress and AD, especially in AA. METHODS: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aß42, Tau, Ptau, Tau/Aß42 (TAR), and Ptau/Aß42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. RESULTS: Higher PSS scores were associated with higher Ptau (ß= 0.43, p = 0.01) and PTAR (ß= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment). CONCLUSION: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity.

Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain.

Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and between RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer's disease, suggesting shared mechanisms.

Publisher Correction: Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Angiotensin converting enzyme inhibitors and cognitive and functional decline in patients with Alzheimer's disease: an observational study.

We previously reported that angiotensin converting enzyme inhibitors (ACEIs) decrease the rate of cognitive decline in elderly patients with hypertension, but their impact on patients with Alzheimer's disease (AD) is not known. A total of 62 elderly patients with AD were enrolled, and 52 completed the study for 6 months. Mini-Mental Status Examination (MMSE), Clock Draw Test (CDT), working memory (Digit Ordering), Instrumental Activities of Daily Living (IADL) scale, and the Screen for Caregiver Burden (SCB) were collected at baseline, 3 months, and 6 months. AD patients receiving ACEI (N = 15) demonstrated a slower rate of decline in digit forward (P = .003) and IADL scale (P = .003) and an improved measure of caregiver burden (P = .04) but not MMSE (P =.15) or CDT (P =.9) compared with those not receiving ACEI after adjusting for other risk factors. This study suggests that use of ACEI in AD patients is associated with slower rate of AD progression. A randomized clinical trial is needed to confirm our finding.

The Relationship Between Cognitive Functioning and the JNC-8 Guidelines for Hypertension in Older Adults.

BACKGROUND: Guidelines for hypertension treatment by the Eighth Joint National Committee (JNC-8) in 2014 recommended a target systolic blood pressure (BP) of <150/<90 mmHg in persons older than 60 years, in contrast to the 2003 JNC-7 recommendations of systolic BP <140 mmHg. This study evaluated the implications of raising the BP target on cognitive functioning and conversion from normal cognition to mild cognitive impairment (MCI). METHODS: This was a longitudinal study of individuals older than 60 years enrolled in the NIH-NIA Alzheimer's Disease Centers. All had normal cognition at baseline. 453 participants were taking BP medications and had readings of <140/<90 mmHg at four annual visits (reference group). Two other groups consisted of participants with either systolic BP of 140-149 mmHg (n = 112) or ≥150 mmHg (n = 280) on three or four annual visits. RESULTS: Compared with the reference and the 140-149 mmHg groups, those with BP ≥150 mmHg exhibited poorer cognitive status by Year 4 on the Mini-Mental State Exam, and they had a higher risk of conversion to MCI. The 140-149 mmHg exhibited poorer performance than the reference group on domains assessing attention and executive functioning. In contrast, their performance was not significantly different from those with BP ≥150 mmHg. CONCLUSIONS: Persons with BP ≥150 mmHg show a faster global cognitive decline and transition to MCI than those with lower BP readings. However, the poor cognitive performance in the attention and executive functioning domains for the 140-149 mmHg group indicates the need for further research evaluating the newer recommended cutoff.

The impact of lifestyle behavior on hypertension awareness, treatment, and control in a southeastern population.

BACKGROUND: We were interested in determining the rates of hypertension awareness, treatment, and control in individuals living in the southeastern United States and evaluating the impact of lifestyle behaviors on these rates. METHODS: This is a cross-sectional survey of a sample of community dwellers in the greater Columbia, South Carolina area. The survey was developed from validated community-based survey questionnaires to evaluate demographic and social history (age, gender, race-ethnicity, income, and education), hypertension history (diagnosis and treatment), and lifestyle behavior (servings of fruits and vegetables [FV] and physical activity [PA] duration and frequency), as well as blood pressure measurement. RESULTS: A total of 763 people (mean +/- standard error age 52.4 +/- 0.7 years; 68% women, 53% African American) agreed to be screened. Of all participants with hypertension (438 [58%]), 82% were aware of their illness and 79% were on treatment. Of all hypertensive participants, 39% had their hypertension controlled below 140/90 mm Hg at the time of the survey. Only 11% reported consuming five or more FV per day and 18% reported PA five or more times per week. African-Americans consumed less FV (P < 0.001) and performed less PA (P < 0.001). Those consuming more FV and exercising more frequently had lower hypertension prevalence and tended to have better control rates. CONCLUSIONS: In a sample of southeastern residents, the control rate was suboptimal despite a relatively high rate of treatment. Low levels of FV consumption and PA were noted especially in African-American patients and may explain this rate.

Improving patient outcomes with ambulatory blood pressure monitoring in elderly with hypertension.

PURPOSE: The purpose of this article is to review the current knowledge regarding ambulatory blood pressure monitoring (ABPM) use in clinical practice and to provide example cases for its use in a hypertension (HTN) specialty clinic. DATA SOURCES: Published research trials, medical literature, and cases from the Center for Senior Hypertension. CONCLUSIONS: The knowledge of ABPM benefits to using ABPM are substantial and improves the care and management of many conditions, including white coat HTN, white coat normotension, resistant, borderline, episodic, paroxysmal HTN, and finally orthostatic hypotension. Third-party payers only cover ABPM for "white coat" HTN. IMPLICATIONS FOR PRACTICE: This article reviews previous studies and explains the benefit to changing our current practice to match the knowledge we have gained through research through case studies.

Dietary calcium lowers the age-related rise in blood pressure in the United States: the NHANES III survey.

This analysis of the third National Health and Nutrition Examination Survey (NHANES III) was designed to investigate the impact of dietary calcium intake on age-related changes in blood pressure and pulse pressure. Data on 17,030 participants 20 years or older (mean age, 48.8+/-0.2 years; 47% male, 42% Caucasian, and 28% African American) were used. Data included demographics, body mass index, blood pressure, and daily dietary calcium. Overall, average calcium intake was 761 mg/day. After adjusting for demographic and anthropomorphic variables, as well as total energy consumption, higher calcium intake was associated with lower rates of age-related increases of systolic blood pressure and pulse pressure (p<0.001). If the calcium intake of the general population were to increase to above 1200 mg, the incidence of isolated systolic hypertension in the elderly might be decreased.

The use of the internet in geriatrics education: results of a national survey of medical geriatrics academic programs.

In order to characterize use of the Internet in medical geriatrics education programs, 130 medical education programs in the U.S. that train medical students, interns, residents, fellows and practicing physicians were asked to complete a survey developed by the Consortium of E-Learning in Geriatrics Instruction (CELGI). Sixty-eight programs (52.3%) returned surveys. Fifty-four (79%) of those responding reported using the Internet specifically for geriatric medical education, and 38 (56%) reported they are developing Internet materials. Twentythree undergraduate, 31 graduate, and 26 continuing medical education programs reported at least 25% of their curriculum was Internet-based. Users and developers of medical geriatric Internet materials had more full-time faculty and nonclinical faculty. The results of our survey indicate that the Internet is being widely used in medical geriatric education.

A randomized, double-blind, controlled trial of vitamin C in the management of hypertension and lipids.

The effect of vitamin C on blood pressure is not well established. This is a randomized, double-blind control trial. Eligible patients were followed for 8 months. Patients were randomized to 500, 1000, or 2000 mg vitamin C. During each visit, a history including medication change was obtained and standardized blood pressure measurements were performed. A 1-week dietary diary was filled out before each visit. Multiple regression analysis and subsequent multiple comparisons were used for data analysis. Fifty-four patients satisfied our criteria and agreed to participate. Thirty-one patients (mean age, 62 +/- 2 years; 52% men, 90% whites) were randomized to the three doses of vitamin C. Overall compliance was 48 +/- 2%. Both mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased during the vitamin C supplementation phase [mean SBP dropped by 4.5 +/- 1.8 mm Hg (P <.05) and DBP by 2.8 +/- 1.2 mm Hg (P <.05)]. There was no difference between the three vitamin C groups (P =.48). This effect was significant for only 1 month of supplementation, but the trend persisted. There was no reported intolerance to vitamin C. There was no change in lipid levels after 6 months of treatment. Vitamin C supplementation lowers blood pressure in mildly hypertensive patients. There is no additional benefit for a higher dose than 500 mg daily. The effect of vitamin C is most likely to be only short term.