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INTRODUCTION: There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants. METHODS: Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2. RESULTS: CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aß)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor ß (sPDGFRß) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aß40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRß and tau were significantly lower in B/AA than NHW. DISCUSSION: Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships. HIGHLIGHTS: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Lesiones del Sistema Vascular , Persona de Mediana Edad , Humanos , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Enfermedades Neuroinflamatorias , Proteínas tau/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeoRESUMEN
INTRODUCTION: In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers. METHODS: Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N = 29, F/M = 17/12) and Non-Hispanic White (N = 47, F/M = 27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aß)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes. RESULTS: Results revealed a significant race × Aß42 interaction in Black Americans: lower Aß42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals. DISCUSSION: Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer's disease risk pathology during middle age, particularly in Black Americans. HIGHLIGHTS: Cerebrospinal fluid (CSF) amyloid beta (Aß)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aß42 in Black Americans. Precuneus may be a hub for early Alzheimer's disease pathology changes detected by functional connectivity.
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Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.
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Nativos Alasqueños , Enfermedad de Alzheimer , Adulto , Humanos , Indio Americano o Nativo de Alaska , Inequidades en Salud , Disparidades en Atención de Salud , Factores de Riesgo , Minorías Sexuales y de Género , Estados Unidos/epidemiología , BlancoRESUMEN
OBJECTIVE: Self-assessment of cognitive abilities can be an important predictor of clinical outcomes. This study examined impairments in self-assessments of cognitive performance, assessed with traditional neuropsychological assessments and novel virtual reality tests among older persons with and without human immunodeficiency virus (HIV) and mild cognitive impairment (MCI). METHODS: One hundred twenty-two participants (82 persons with HIV; 79 MCI+) completed a traditional neuropsychological battery, DETECT virtual reality cognitive battery, and self-reported their general cognitive complaints, depressive symptoms, and perceptions of DETECT performance. Relationships between DETECT performance and self-assessments of performance were examined as were the correlations between general cognitive complaints and performance. These relations were evaluated across HIV and MCI status, considering the associations of depressive symptoms, performance, and self-assessment. RESULTS: We found no effect of HIV status on objective performance or self-assessment of DETECT performance. However, MCI+ participants performed worse on DETECT and traditional cognitive tests, while also showing a directional bias towards overestimation of their performance. MCI- participants showed a bias toward underestimation. Cognitive complaints were reduced compared to objective performance in MCI+ participants. Correlations between self-reported depressive symptoms and cognitive performance or self-assessment of performance were nonsignificant. CONCLUSIONS: MCI+ participants underperformed on neuropsychological testing, while overestimating performance. Interestingly, MCI- participants underestimated performance to approximately the same extent as MCI+ participants overestimated. Practical implications include providing support for persons with MCI regarding awareness of limitations and consideration that self-assessments of cognitive performance may be overestimated. Similarly, supporting older persons without MCI to realistically appraise their abilities may have clinical importance.
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Disfunción Cognitiva , Infecciones por VIH , Humanos , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Cognición , Pruebas Neuropsicológicas , Autoinforme , Infecciones por VIH/complicacionesRESUMEN
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. 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. 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. HIGHLIGHTS: Black individuals have been shown to have higher Alzheimer's disease (AD) rates than those who are White. Some co-morbidities are known to increase AD risk. Among those In Medicare data with no co-morbidities, Black individuals have less risk than those who are White. Among those with co-morbidities, Black individuals have higher rates than those who are White. Hypertension results in a much stronger increase in AD risk for Black versus White individuals.
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Enfermedad de Alzheimer , Hipertensión , Humanos , Anciano , Estados Unidos/epidemiología , Enfermedad de Alzheimer/epidemiología , Medicare , Comorbilidad , Hipertensión/epidemiología , BlancoRESUMEN
INTRODUCTION: It is unclear if sex differences exist in cognitive disease progression in mild cognitive impairment (MCI) and dementia associated with atrial fibrillation (AF). METHODS: Using a variety of statistical methods, we examined sex differences between AF and neuropsychological tests and cognitive disease progression, using the National Alzheimer's Coordinating Center data (N = 43,630). RESULTS: AF is associated with higher odds of dementia (odds ratio [OR] 3.00, 95% confidence interval [CI] [1.22, 7.37] in women and MCI in women (OR 3.43, 95% CI [1.55, 7.55]) versus men. Women with AF and normal baseline cognition had a higher risk of disease progression (hazard ratio [HR] 1.26, 95% CI [1.06, 1.50]) from normal to MCI and from MCI to vascular dementia (HR3.27, 95% CI [1.89, 5.65]) than men with AF or men and women without AF. DISCUSSION: AF was associated with more rapid progression to MCI and dementia in women, but more research is needed to confirm these findings.
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Enfermedad de Alzheimer , Fibrilación Atrial , Trastornos del Conocimiento , Humanos , Femenino , Masculino , Fibrilación Atrial/epidemiología , Enfermedad de Alzheimer/epidemiología , Progresión de la Enfermedad , CogniciónRESUMEN
BACKGROUND: The Dominantly Inherited Alzheimer Network (DIAN) is a longitudinal observational study that collects data on cognition, blood pressure (BP), and other variables from autosomal-dominant Alzheimer's disease mutation carriers (MCs) and non-carrier (NC) family members in early to mid-adulthood, providing a unique opportunity to evaluate BP and cognition relationships in these populations. METHOD: We examined cross-sectional and longitudinal relationships between systolic and diastolic BP and cognition in DIAN MC and NC. RESULTS: Data were available from 528 participants, who had a mean age of 38 (SD = 11) and were 42% male and 61% MCs, at a median follow-up of 2 years. Linear-multilevel models found only cross-sectional associations in the MC group between higher systolic BP and poorer performance on language (ß = -0.181 [-0.318, -0.044]), episodic memory (-0.212 [-0.375, -0.049]), and a composite cognitive measure (-0.146 [-0.276, -0.015]). In NCs, the relationship was cross-sectional only and present for language alone. DISCUSSION: Higher systolic BP was cross-sectionally but not longitudinally associated with poorer cognition, particularly in MCs. BP may influence cognition gradually, but further longitudinal research is needed.
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Enfermedad de Alzheimer , Humanos , Masculino , Adulto , Femenino , Estudios Transversales , Presión Sanguínea , Cognición , Mutación/genéticaRESUMEN
INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]). DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/patología , Microglía/patología , Inflamación , Apolipoproteínas E/genéticaRESUMEN
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 RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. RESULTS: A total of 563 individuals reported RAS-AHM use and 149 reported other-AHM 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. CONCLUSION: In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.
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Disfunción Cognitiva , Demencia , Diabetes Mellitus Tipo 2 , Humanos , Antihipertensivos/uso terapéutico , Sistema Renina-Angiotensina , Sobrepeso/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/psicología , Cognición , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & controlRESUMEN
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-ß. 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-ß 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.
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Disfunción Cognitiva , Demencia , Microbioma Gastrointestinal , Isoflavonas , Antioxidantes , Disfunción Cognitiva/prevención & control , Demencia/prevención & control , Equol/metabolismo , Receptor beta de Estrógeno , Humanos , Isoflavonas/metabolismo , Isoflavonas/farmacología , Fitoestrógenos/metabolismo , Receptores de EstrógenosRESUMEN
As the health care and well-being of sexual and gender minority (SGM; i.e., lesbian, gay, bisexual, and/or transgender or gender non-binary) people in the United States receive federal and local-level attention, SGM older adults and caregivers continue to be left out of important health policy and care conversations. The current article describes policy issues and affirmative strategies related to inclusive care practices among SGM older adults and caregivers. In addition to the broader policies considered related to health and well-being, we include a discussion of local-level policy strategies to mitigate discrimination and promote inclusive care for SGM older adults and caregivers. [Journal of Gerontological Nursing, 48(12), 6-15.].
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Enfermería Geriátrica , Minorías Sexuales y de Género , Personas Transgénero , Femenino , Anciano , Humanos , Conducta Sexual , Política de SaludRESUMEN
The current article presents results of a scoping review of international research on the health and health care needs of sexual and gender minority (SGM) older adults. Electronic databases and related resources were used to identify empirical and review studies published during the past 10 years. We reviewed 33 peer-reviewed articles from 19 countries. Findings were organized using the SGM Health Disparities Research Framework, which highlights factors at individual, interpersonal, community, and societal levels that impact health. Overall, historic and current environmental factors, including stigma, discrimination, and social exclusion, played an important role in SGM older adults' health, health care access, and use of related aging and social services. There is a critical need for training and future research, and health professionals are needed to advance gerontological health and health care research and improve the health and care of SGM older adults globally. [Journal of Gerontological Nursing, 48(4), 13-20.].
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Minorías Sexuales y de Género , Anciano , Atención a la Salud , Personal de Salud , Humanos , Conducta Sexual , Estigma SocialRESUMEN
AIMS: We aim to establish the feasibility and acceptability of the Tele-STELLA (Support via Telehealth: Living and Learning with Advancing Alzheimer's Disease and Related Dementias) intervention. We will also assess the efficacy of the intervention in reducing the frequency of behavioural symptoms of dementia as well as family Care Partner reactivity to the symptoms. DESIGN: This is a multi-component, quasi-experimental study that focuses on facilitating effective management of behavioural symptoms that occur in the later stages of dementia. METHODS: Family Care Partners (n = 124) for persons with Alzheimer's disease will participate in two 8-week videoconferencing components that address behavioural symptoms-in both the persons with Alzheimer's disease and their Care Partners. In the first component ('Nova'), Care Partners work with one nurse for an hour/week for 4 weeks, then they join a small group for another 4 weeks. In the second component ('Constellation'), Care Partners work in a larger group to hone skills and knit supportive relationships. Behavioural symptom frequency and Care Partner reactivity to the behaviours will be measured prior to, during and after the intervention. The study is funded by the United States National Institute on Aging (R01AG067546); funding was initiated as on February, 2021. DISCUSSION: Tele-STELLA fills a gap in current videoconference-based psychoeducational interventions in that it offers real-time interaction with nurses and peers. The intervention was designed with feedback by pilot participants. This study will assess Tele-STELLA in its current, novel format; thus, preparing it for a larger, future randomized controlled trial. IMPACT: Tele-STELLA addresses symptoms that occur in the later stages of dementia, providing families with tools to facilitate effective behavioural management. Because Tele-STELLA is implemented via videoconferencing, it targets Care Partners who face barriers to support, such as cost and transportation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (#NCT04627662).
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Enfermedad de Alzheimer , Telemedicina , Enfermedad de Alzheimer/terapia , Terapia Conductista , Consejo , HumanosRESUMEN
High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer's disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.
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Enfermedad de Alzheimer , Hipertensión/sangre , Hipertensión/líquido cefalorraquídeo , Anamnesis , Sodio/sangre , Sodio/líquido cefalorraquídeo , Anciano , Presión Sanguínea , Femenino , Georgia/epidemiología , Humanos , Hipertensión/inducido químicamente , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Cloruro de Sodio Dietético/efectos adversosRESUMEN
Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.
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COVID-19/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/fisiopatología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Georgia , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life or 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, or AD dementia. After determining baseline interleukin (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 postmortem IL-9-related gene expression profiles in the publicly 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 perivascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in 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 nongenetic factors need to be considered in future AD research involving unique populations. ANN NEUROL 2019;86:407-418.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Negro o Afroamericano , Encéfalo/metabolismo , Disfunción Cognitiva/líquido cefalorraquídeo , Interleucina-9/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población BlancaRESUMEN
BACKGROUND: Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women. METHODS AND FINDINGS: KEEPS, a randomized, double-blinded, placebo-controlled clinical trial, was conducted at nine US academic centers. Of the 727 women enrolled in KEEPS, 693 (95.3%) participated in the ancillary KEEPS-Cog, with 220 women randomized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens (o-CEE) plus 200 mg/d micronized progesterone (m-P) for the first 12 d of each month, 211 women randomized to receive 50 µg/d transdermal estradiol (t-E2) plus 200 mg/d m-P for the first 12 d of each month, and 262 women randomized to receive placebo pills and patches. Primary outcomes included the Modified Mini-Mental State examination; four cognitive factors: verbal learning/memory, auditory attention/working memory, visual attention/executive function, and speeded language/mental flexibility; and a mood measure, the Profile of Mood States (POMS). MHT effects were analyzed using linear mixed-effects (LME) models, which make full use of all available data from each participant, including those with missing data. Data from those with and without full data were compared to assess for potential biases resulting from missing observations. For statistically significant results, we calculated effect sizes (ESs) to evaluate the magnitude of changes. On average, participants were 52.6 y old, and 1.4 y past their last menstrual period. By month 48, 169 (24.4%) and 158 (22.8%) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment (3MS and cognitive factors) and mood evaluations (POMS), respectively. However, because LME models make full use all available data, including data from women with missing data, 95.5% of participants were included in the final analysis (n = 662 in cognitive analyses, and n = 661 in mood analyses). To be included in analyses, women must have provided baseline data, and data from at least one post-baseline visit. The mean length of follow-up was 2.85 y (standard deviation [SD] = 0.49) for cognitive outcomes and 2.76 (SD = 0.57) for mood outcomes. No treatment-related benefits were found on cognitive outcomes. For mood, model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment, compared to women on placebo. The model estimate for the depression subscale was -5.36 × 10(-2) (95% CI, -8.27 × 10(-2) to -2.44 × 10(-2); ES = 0.49, p < 0.001) and for the anxiety subscale was -3.01 × 10(-2) (95% CI, -5.09 × 10(-2) to -9.34 × 10(-3); ES = 0.26, p < 0.001). Mood outcomes for women randomized to t-E2 were similar to those for women on placebo. Importantly, the KEEPS-Cog results cannot be extrapolated to treatment longer than 4 y. CONCLUSIONS: The KEEPS-Cog findings suggest that for recently postmenopausal women, MHT did not alter cognition as hypothesized. However, beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE, but not with 4 y of t-E2. The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles. TRIAL REGISTRATION: ClinicalTrials.gov NCT00154180 and NCT00623311.
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Cognición/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Trastornos del Humor/tratamiento farmacológico , Posmenopausia , Método Doble Ciego , Estradiol/uso terapéutico , Estrógenos Conjugados (USP)/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Progesterona/uso terapéutico , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Estados UnidosRESUMEN
Cerebral blood flow (CBF) provides an indication of the metabolic status of the cortex and may have utility in elucidating preclinical brain changes in persons at risk for Alzheimer's disease (AD) and related diseases. In this study, we investigated CBF in 327 well-characterized adults including patients with AD (n = 28), patients with amnestic mild cognitive impairment (aMCI, n = 23), older cognitively normal (OCN, n = 24) adults, and asymptomatic middle-aged adults (n = 252) with and without a family history (FH) of AD. Compared with the asymptomatic cohort, AD patients displayed significant hypoperfusion in the precuneus, posterior cingulate, lateral parietal cortex, and the hippocampal region. Patients with aMCI exhibited a similar but less marked pattern of hypoperfusion. Perfusion deficits within the OCN adults were primarily localized to the inferior parietal lobules. Asymptomatic participants with a maternal FH of AD showed hypoperfusion in hippocampal and parietofrontal regions compared with those without a FH of AD or those with only a paternal FH of AD. These observations persisted when gray matter volume was included as a voxel-wise covariate. Our findings suggest that having a mother with AD might confer a particular risk for AD-related cerebral hypoperfusion in midlife. In addition, they provide further support for the potential utility of arterial spin labeling for the measurement of AD-related neurometabolic dysfunction, particularly in situations where [18F]fluorodeoxyglucose imaging is infeasible or clinically contraindicated.
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Enfermedad de Alzheimer/patología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Hijo de Padres Discapacitados , Relaciones Madre-Hijo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Mapeo Encefálico , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: Incidence and prevalence of atrial fibrillation (AF), a risk factor of dementia, have been increasing over time. Oral anticoagulation reduces risk of stroke and other negative outcomes of AF and may reduce dementia health inequities. The objective of this study was to estimate dementia incidence in patients with newly-diagnosed AF and taking an anticoagulant as use of direct oral anticoagulants (DOACs) increased. METHODS: We used a retrospective cohort design with annual incident AF cohorts of community-dwelling Medicare Fee-for-Service beneficiaries, enrolled in Parts A, B, and D from 2007 to 2017. The sample was limited to beneficiaries aged 67 years and older with incident AF; no prior dementia; and use of anticoagulants warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban in year t. RESULTS: A total of 1,083,338 beneficiaries were included in the study, 58.5% female, with mean (SD) age 77.2 (6.75) years. Among anticoagulated, incident AF cohorts, use of DOACs increased from 10.6% in their first year of availability (2011) to 41.4% in 2017. Among incident AF cohorts taking any oral anticoagulant, 3-year dementia incidence did not change significantly over the cohorts after adjusting for confounders. For example, incidence was 9.1% (95% CI 8.9-9.4) among White persons diagnosed with AF in 2007 and 2008 and 8.9% (95% CI 8.7-9.1) in 2017. Across cohorts, dementia incidence was consistently highest for Black persons, followed by American Indian/Alaska Native and White persons, and lowest for Asian persons. In 2017, 10.9% (95% CI 10.4-11.3) of Black persons in the cohort developed dementia within 3 years, 9.4% (95% CI 8.0-10.9) of American Indian/Alaska Native, 8.9% (95% CI 8.7-9.1) of White, 8.7% (95% CI 8.2-9.1) of Hispanic, and 6.9% (95% CI 6.4-7.4) of Asian persons. Across race/ethnicity, 3-year stroke risk decreased consistently over time; however, the increasing availability of DOACs did not alter the trend. DISCUSSION: Increased use of DOACs among incident AF cohorts from 2007 to 2017 was not associated with significant declines in dementia or stroke risk. Consideration of similar stroke and dementia risk, as well as differences in cost, is warranted when weighing the risks and benefits of available oral anticoagulants.
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Anticoagulantes , Fibrilación Atrial , Demencia , Medicare , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Anciano , Femenino , Masculino , Demencia/epidemiología , Incidencia , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Estudios Retrospectivos , Estados Unidos/epidemiología , Administración Oral , Dabigatrán/uso terapéutico , Rivaroxabán/uso terapéutico , Estudios de Cohortes , Warfarina/uso terapéuticoRESUMEN
INTRODUCTION: Past Alzheimer's disease and related dementias (ADRD) research has not considered ways to ensure the representation of diverse sexual and gender minorities. This study used concept mapping (CM) to identify strategies for engaging and recruiting LGBTQIA+ older adults living with memory loss and their caregivers into ADRD research. METHODS: CM, involving brainstorming, thematic analysis, and rating of strategies, was conducted with 46 members from one national and three local community advisory boards. Data was analyzed using The Concept Systems Global MAX™ web platform. RESULTS: One hundred twenty-two solutions were identified from June through December 2022, and represented five key themes: aging focused, LGBTQIA+ specific, memory loss and caregiving support focused, physical advertisements, and other media. Promising strategies included partnering with LGBTQIA+ health centers, attending social groups for older adults, and increasing community representation in marketing. DISCUSSION: Tailored strategies, building trust, and community involvement are essential for engaging LGBTQIA+ individuals living with memory loss or ADRD and their caregivers in ADRD-focused research. Highlights: Innovative ways to ensure the inclusion of LGBTQIA+ older adults in Alzheimer's disease and related dementias (ADRD) research can be bolstered through collaboration with key community stakeholders.Promising strategies for recruitment and engagement include partnering with LGBTQIA+ centers, attending social groups for older adults, and ensuring diverse representation in marketing.Tailored recruitment and engagement strategies are crucial for building trust with LGBTQIA+ populations to increase participation in ADRD research.