Introduction: Alzheimer's disease (AD) incidence is thought to be higher among Black than White individuals.​

Methods: We studied the US Medicare population from 2000 to 2018. Cox regression was used to determine the roles of race and co-morbidities for AD incidence.

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Results: We studied 11,880,906 Medicare beneficiaries, with 774,548 AD cases. Hazard ratios (HRs) by increasing numbers of co-morbidities (1–7) were 1.51, 2.00, 2.55, 3.16, 2.89, 4.77, and 5.65. Among those with no co-morbidities, Black individuals had a lower rate than those who are White (HR = 0.69), while among those with one more co-morbidities, Black individuals had a higher rate (HR = 1.19). The presence of hypertension increased AD rates by 14% for White individuals, but 69% for those who are Black.

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Discussion: More co-morbidities was strongly associated with higher AD rates. The higher rates for Black versus White individuals was apparent only for those with co-morbidities and appears driven both by more co-morbidities, and the greater effect of hypertension.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-β. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-β is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Aims: This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors.

Methods: The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model, adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year.

Results: A total of 426 089 persons were included in the primary analysis, with 45 541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 0.85–1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% confidence interval 0.50–0.72).

Conclusions: A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.

Aim: To determine whether antihypertensive medication (AHM) acting through the
renin angiotensin system (RAS-AHM), compared with other AHM, can mitigate
effects on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM).

Materials and Methods: This secondary analysis of the randomized controlled Action
for Health in Diabetes (Look AHEAD) study included 712 community-dwelling
participants who were followed over 15 years. Logistic regression was used to relate
RAS-AHM use to cognitive impairment, and linear regression was used to relate RASAHM use to domain-specific cognitive function after adjusting for potential
confounders.

Results: A total of 563 individuals reported RAS-AHM use and 149 reported otherAHM use during the study. RAS-AHM users have college or higher education (53%),
had higher baseline glycated haemoglobin (57 mmol/mol), and reported higher diabetes medication use (86%), while other-AHM users were more likely to be White
(72%), obese (25%) and to have cardiovascular history (19%). RAS-AHM use was not
associated with a reduced risk of dementia compared with other-AHM use. We did
observe better executive function (Trail Making Test, part B, P < 0.04), processing
speed (Digit Symbol Substitution Test, P < 0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, P < 0.005), and composite score (P < 0.008) among
RAS-AHM users compared with other-AHM users.

Objective: Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer’s disease (AD), and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life, and whether race modifies other AD-related biomarkers such as inflammatory proteins.

Methods: We performed multiplex cytokine analysis in a healthy middle-aged cohort with family history of AD (n=68) and an older cohort (n=125) with normal cognition (NC), mild cognitive impairment (MCI), or AD dementia. After identifying baseline IL-9 level and AD-associated IL-9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL-9 in brains of African Americans and Caucasians (n=38), and analyzed post-mortem IL-9-related gene expression profiles in the publically available Mount Sinai cohort (26 African Americans and 180 Caucasians).

Results: Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p-Tau181, and IL-9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL-9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed peri-vascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in two independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL-9 upregulation only in African Americans but not Caucasians.

Interpretation: Baseline and AD-associated IL-9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and non-genetic factors need to be considered in future AD research involving unique populations.

Background: Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management.

Methods: In a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities.

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Findings: RAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women.

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Conclusion: Hypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance.

Background: Individuals taking renin angiotensin system (RAS) acting antihypertensives exhibit slower cognitive decline and are less likely to progress from mild cognitive impairment (MCI) to Alzheimer’s disease (AD), but the mechanism remains unclear.

Objective: We tested the hypothesis that individuals taking RAS acting antihypertensives exhibit less AD-related neuropathology and slower disease progression than individuals taking non-RAS acting antihypertensives.

Method: Participants included 83 individuals with MCI who were taking an antihypertensive at baseline, had at least two follow-up visits, and had postmortem neuropathological data. Participants were old (M = 83.1 years), 32% male, well educated (M = 15.7 years), and 9.2% Black.

Results: RAS medication users (N= 38) were less likely to progress to AD than non-RAS users (N= 45). RAS users exhibited fewer neurofibrillary tangles than non-RAS users in the hippocampal CA1 region (p < 0.01), entorhinal cortex (p = 0.03), and the angular gyrus, inferior temporal, mid-frontal cortex, and superior frontal (p = 0.01).

Conclusion: : Prevention or clearance of neurofibrillary tangles represents a mechanism by which RAS medications may slow disease progression.

Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. The role of caring for someone with AD frequently falls to female family members, often daughters. The burden of caregiving can increase stress and anxiety and cause health decline in the caregiver. The combination of ethnicity-related genetic factors promoting the development of dementias among African-Americans (AA) and the increased risk among women for developing AD means that AA women who are caregivers of a parent with AD are at great risk for developing dementias including AD. The proposed study would compare the cognitive, motor, and psychosocial benefits of a well-established 12 week, 20-lesson adapted Argentine Tango intervention (N=30) to a no-contact control group (N=10) in middle-aged (45-65 years) AA women who are caregivers of a parent with AD in the metro Atlanta area.

Background: African Americans (AA) are more likely to develop Alzheimer’s disease (AD) than Caucasians (CC). Dietary modification may have the potential to reduce the risk of developing AD.

Objective: The objective of this study is to investigate the relationship between Southern and Prudent diet patterns and cognitive performance in individuals at risk for developing AD.

Design: Cross-sectional observational study.

Participants: Sixty-six cognitively normal AA and CC individuals aged 46–77 years with a parental history of AD were enrolled.

Measurements: Participants completed a Food Frequency questionnaire, cognitive function testing, which consisted of 8 neuropsychological tests, and cardiovascular risk factor assessments, including evaluation of microvascular and macrovascular function and ambulatory blood pressure monitoring.

Results: Results revealed a relationship between the Southern diet and worse cognitive performance among AAs. AAs who consumed pies, mashed potatoes, tea, and sugar drinks showed worse cognitive performance (p<0.05) compared with CCs. In addition, gravy (p=0.06) and cooking oil/fat (p=0.06) showed negative trends with cognitive performance in AAs. In both CC and AA adults, greater adherence to a Prudent dietary pattern was associated with better cognitive outcomes. Cardiovascular results show that participants are overall healthy. AAs and CCs did not differ on any vascular measure including BP, arterial stiffness and endothelial function.

Conclusion: Research shows that dietary factors can associate with cognitive outcomes. This preliminary crosssectional study suggests that foods characteristic of the Southern and Prudent diets may have differential effects on cognitive function in middle-aged individuals at high risk for AD. Results suggest that diet could be a non-pharmaceutical tool to reduce cognitive decline in racially diverse populations. It is possible that the increased prevalence of AD in AA could be partially reduced via diet modification.

Background: Several studies have shown higher Alzheimer’s disease (AD) incidence rates are in African-Americans (AAs) than Caucasians (CCs). If this finding is consistent across studies, it raises important etiologic questions regarding factors responsible for this discrepancy. It also affects the likely public health burden of AD in the US in the future, as the non-Caucasian population becomes the majority.

Objective: Estimate the AA/CC rate ratio for AD incidence across all available studies.

Methods: We conducted a meta-analysis of population-based studies for the rate ratio (RR) of AD incidence for AAs versus CCs, after identifying six relevant studies from the literature. We calculated an AA/CC rate ratio across all studies using inverse-variance weighting, and assessed inter-study heterogeneity. Using these incidence data, as well as data on survival after diagnosis, and on all-cause mortality, we also estimated the US prevalence of AD among AAs and CCs.

Results: There were six population-based studies with data comparing AD incidence between AAs and CCs, with an estimated 370 AA and 640 CC incident cases. The meta-analysis RR showed that the AD rate for AAs was 64% higher than for CCs (RR = 1.64 (95% CI 1.35–2.00)), with no evidence of heterogeneity. We estimated the current US AD prevalence for ages 65–90 to be 5.5% for CCs, and 8.6% for AAs (prevalence ratio 1.56).

Conclusion: AAs have an increased risk of incident and prevalent AD compared to CCs for reasons which are unknown, but are hypothesized to reflect biological, psychological, and socioeconomic factors.

Research shows that certain antihypertensives taken during midlife confer Alzheimer’s disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including CSF amyloid β levels (Aβ) and ACE activity, arterial function and cognition in participants with a parental history of AD.

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This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier (BBB) crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ1–42 and ACE activity, arterial function and cognition.

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Participants were middle-aged (mean 54yrs) highly educated (mean 15.4yrs), and included 50% men and 50% APOEε4 carriers. While results did not show a treatment effect on CSF Aβ1–42 (p=0.836), data revealed that ramipril can inhibit CSF ACE activity (p=0.009) and improve blood pressure (BP), however there were no differences between groups in arterial function or cognition.

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In this study, ramipril therapy inhibited CSF ACE activity and improved BP, but did not influence CSF Aβ1–42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of Angiotensin II-mediated inhibition of acetylcholine.

Research indicates that certain antihypertensive medications alter Alzheimer’s disease (AD) biomarkers in Caucasians. The renin angiotensin system (RAS) regulates blood pressure (BP) in the body and the brain and may directly influence AD biomarkers, including Aβ neuropathology, cerebral blood flow (CBF) and inflammatory markers. This hypothesis is supported by studies, including ours, showing that antihypertensives targeting the RAS reduce the risk and slow the progression of AD in Caucasians.
While mounting evidence supports a protective role of RAS medications in Caucasians, this mechanism has not been explored in African Americans.
 

To assess the mechanism by which RAS medications modify the brain RAS, CSF Aβ, CBF, and inflammatory markers in African Americans, we are conducting an eight month, Phase Ib randomized, placebo controlled trial, enrolling 60 middle-aged (45–70yrs), non-demented individuals, at risk for AD by virtue of a parental history.

Participants include normotensive and treated hypertensives that have never been exposed to a RAS medication. Participants are randomized (1:1:1) by gender and BP medication use (yes/no)to one of three groups: placebo, or 20mg, or 40mg telmisartan (Micardis), to determine the dose required to penetrate the CNS. Our overarching hypothesis is that, compared to placebo, both doses of telmisartan will penetrate the CNS and produce salutary, dose dependent effects on the brain RAS as well as CSF Aβ, CBF and CSF inflammatory markers in African Americans, over eight months. This manuscript describes the trial
rationale and design.

Antihypertensives that modulate the renin-angiotensin system (RAS) on AD conversion in those with MCI has not been explored. Evidence suggests that blood-brain-barrier (BBB) permeability is necessary for these effects. We assessed the impact of RAS modulation on conversion to AD and cognitive decline in those with MCI, and the impact of BBB permeability and race on these associations.

We analyzed data from the National Alzheimer’s Coordinating Center from the NIA-funded Alzheimer’s Disease Centers. We included individuals receiving antihypertensives with MCI at baseline and who had cognitive assessments on at least 2 follow-up visits. Outcomes included conversion to AD and cognitive and functional decline.

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Of 784 participants (M=75 years, 48% men), 488 were receiving RAS medications. RAS users were less likely to convert to AD (33% vs 40%; p=0.04) and demonstrated slower decline on the Clinical Dementia Rating sum-of-boxes (CDR-SOB, p<0.01) and Digit Span Forward (p=0.02) than non-RAS users. BBB-crossing RAS medications were associated with slower cognitive decline on the CDR-SOB, (p<0.01), the Mini Mental Status Examination, (p<0.01) and the Boston Naming test (p<0.01). RAS medications were somewhat associated with cognitive benefits in African Americans, more so than Caucasians. (MMSE (p=0.05) category fluency (p=0.04) and Digit Span Backwards, p=0.03)).

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RAS-modulating medications were associated with less conversion to AD. BBB permeability may produce additional cognitive benefit, and African Americans may benefit moreso from RAS-modulation than Caucasians. Results highlight the need for trials investigating RAS modulation during prodromal disease stages.

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).

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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.

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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.

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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.

Background: Subjective cognitive and functional limitations are early markers of future dementia and physical disability. Hypertension may increase the risk of dementia; however, the magnitude and significance of subjective limitations in the hypertensive US population are unknown, particularly in African Americans who bear the greatest burden of hypertension. Our objectives were to assess the prevalence and racial disparity of subjective cognitive and functional limitations and their impact on mortality in the hypertensive US population.

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Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2010 (N = 28,477; 31% with hypertension; 11% African American), which included blood pressure measurement, self-reported cognitive and functional (physical and non-physical) limitations, and all-cause mortality. Complex survey regression models were used.

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Results: In the United States, 8% of the hypertensive population reported cognitive and 25% reported functional limitations (vs. 5.7% and 15% respectively in the non-hypertensive population, P < 0.0001). Hypertensive African Americans carried the highest burden of cognitive (11%, P = 0.01) and functional (27%, P = 0.03) limitations compared to non-hypertensive African Americans and to non-African Americans. All-cause mortality was significantly higher in hypertensive individuals who reported cognitive or functional limitations (P < 0.0001 for both) relative to those without either.

Conclusion: The prevalence of cognitive and functional disability is larger in the US hypertensive population compared to the non-hypertensive population. African Americans with hypertension carry a disproportionate burden of these limitations. Individuals with hypertension who report cognitive or functional symptoms have higher all-cause mortality and query about these symptoms should be part of hypertension evaluation.

Background: Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management.

Methods: In a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities.

Findings: RAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women.

Conclusion: Hypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance.

Purpose: Art interventions have demonstrated holistic benefits for persons living with dementia and their caregivers. In this article, we describe the results of a pilot photojournalism program for 10 unpaid caregivers of persons living with dementia, with respect to caregivers’ experience in the program and their psychological well-being. Design: Caregivers participated in four sessions led by a professional photojournalist who taught principles of photography. Between the sessions, caregivers took photographs that represented what caregiving meant to them using digital cameras provided in the program. During the sessions, instruction was interspersed with discussion of caregivers’ photographs. Method: Caregiver burden and depressive symptoms were measured pre- and postprogram. Qualitative exploration included sessions’ observations, viewing caregivers’ photographs, and recording caregivers’ accompanying comments. Findings: For participants with pre- and postprogram data, caregiver burden decreased significantly (p = .037). For caregivers with pre- and postprogram data, depressive symptoms decreased nonsignificantly (p = .066). Clinically meaningful reductions in caregiver burden and depressive symptoms were attained. Qualitative findings highlighted caregivers’ strong engagement with the project, the facilitator, and other participants, and reflection on multiple aspects of their experience. Conclusions: This intervention helped caregivers creatively communicate their exp

Background: Accurate serological assays can improve the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but few studies have compared performance characteristics between assays in symptomatic and recovered patients.

Methods: We recruited 32 patients who had 2019 coronavirus disease (COVID-19; 18 hospitalized and actively symptomatic, 14 recovered mild cases), and measured levels of IgM (against the full-length S1 or the highly homologous SARS-CoV E protein) and IgG (against S1 receptor binding domain [RBD]). We performed the same analysis in 103 pre-2020 healthy adult control (HC) participants and 13 participants who had negative molecular testing for SARS-CoV-2.

Results: Anti-S1-RBD IgG levels were very elevated within days of symptom onset for hospitalized patients (median 2.04 optical density [OD], vs. 0.12 in HC). People who recovered from milder COVID-19 only reached similar IgG levels 28 days after symptom onset. IgM levels were elevated early in both groups (median 1.91 and 2.12 vs. 1.14 OD in HC for anti-S1 IgM, 2.23 and 2.26 vs 1.52 in HC for anti-E IgM), with downward trends in hospitalized cases having longer disease duration. The combination of the two IgM levels showed similar sensitivity for COVID-19 as IgG but greater specificity, and identified 4/10 people (vs. 3/10 by IgG) with prior symptoms and negative molecular testing to have had COVID-19.

Conclusions: Disease severity and timing both influence levels of IgM and IgG against SARS-CoV-2, with IgG better for early detection of severe cases but IgM more suited for early detection of milder cases.

We read with interest Huang and colleagues’ description of early patients with 2019 novel coronavirus in China, their plasma inflammatory protein profiles, and the clinical and biochemical distinctions from SARS.1 We have routinely analyzed inflammatory protein levels in healthy aging, neurological disorders, and infectious diseases over 10 years,2-5 and we express the strongest caution in postulating therapeutic protocols based on uncontrolled plasma cytokine analysis. Plasma biomarkers (including those measured here) are gaining popularity due to ease of phlebotomy and availability of commercial assays, but their associations with disease are also notoriously difficult to reproduce across laboratories, cohorts, and assay platforms even in well-controlled settings. Reasons for this include non-standard protocols to generate plasma (from whole blood), unpublished half-lives for most proteins in blood (minutes to days), proprietary methods for quantitation (antigenic site for antibodies, peptide fragment for mass spectrometry), and absence of high quality reference values from well-characterized healthy subjects. Plasma cytokines independent of demographic factors are also highly correlated entities in health (Fig 1A, B) as well as disease, and false associations can in turn result from effects of age or race (Fig 1C, D). Thus, elevated Th2-related cytokines in 2019-nCoV better inform an intact Th1-Th2 axis than putative efficacy of immunomodulatory therapies. If blood cytokine profile (with or without immunophenotyping) are considered for biomarkers to complement drug development or clinical monitoring, we recommend with the greatest urgency the creation of an international reference laboratory to enhance rigor and translatability.

Background: The rate of AD for African Americans (AAs) is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress, and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs.

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Objective: Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race.

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Methods: We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound, and cognitive testing.

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Results: While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less cerebrospinal fluid tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, race significantly modified the relationship between total tau, phospho-tau, and Trails B, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs.

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Conclusion: In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.