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INTRODUCTION: We aimed to characterize the COVID-19 pandemic's relationship with enrollment in US Alzheimer's Disease Research Centers (ADRCs). METHODS: Using data on 10,105 participants from 30 ADRCs, we conducted interrupted time series analyses to assess the relationship of the pandemic with enrollment and calculate projected dates of enrollment recovery. RESULTS: Participants enrolled during the pandemic (vs pre-pandemic) were more likely to have dementia and be referred by health professionals. The pandemic was associated with a 77% drop in enrollment, with projected trend recovery in March 2024 and 100% recovery in September 2024. COVID was associated with a 91% drop in Black/African American participants, compared to 71% in White participants. Enrollment of both Hispanic and female participants was declining 1.4% and 0.3%/month pre-pandemic. DISCUSSION: Funders and researchers should account for ongoing COVID-19 impact on ADRD research enrollment. Strategies to speed enrollment recovery are needed, especially for Black/African American and Hispanic groups. HIGHLIGHTS: Tested COVID pandemic association with enrollment at Alzheimer's Disease Research Centers. During versus pre-pandemic enrollees differed on demographic and clinical variables. Interrupted time series analyses: immediate 77% drop in enrollment related to COVID. Recovery projections: trend recovery in March 2024, 100% recovery in September 2024. Enrollment of African American and Hispanic participants should be prioritized.
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Doença de Alzheimer , COVID-19 , Feminino , Humanos , Doença de Alzheimer/epidemiologia , Negro ou Afro-Americano , COVID-19/epidemiologia , Hispânico ou Latino , Pandemias , Brancos , MasculinoRESUMO
INTRODUCTION: Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D). METHODS: Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model. RESULTS: Among 1393 participants, 104 developed dementia over a 4-year median follow-up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, -3.2%; 95% CI, -6.2% to -0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non-steroidal anti-inflammatory drugs, and antidepressant use. DISCUSSION: Metformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.
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Demência , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Heterogeneidade da Eficácia do Tratamento , Demência/tratamento farmacológico , Demência/epidemiologia , Demência/etiologiaRESUMO
INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.
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INTRODUCTION: White matter hyperintensities (WMH) may promote clinical Alzheimer's disease (AD) disparities between Black American (BA) and non-Hispanic White (nHW) populations. Using a novel measurement, unhealthy white matter connectivity (UWMC), we interrogated racialized group differences in associations between WMH in AD pathology-affected regions and cognition. METHODS: UWMC is the proportion of white matter fibers that pass through WMH for every pair of brain regions. Individual regression models tested associations of UWMC in beta-amyloid (Aß) or tau pathology-affected regions with cognition overall, stratified by racialized group, and with a racialized group interaction. RESULTS: In 201 older adults ranging from cognitively unimpaired to AD, BA participants exhibited greater UWMC and worse cognition than nHW participants. UWMC was negatively associated with cognition in 17 and 5 Aß- and tau-affected regions, respectively. Racialization did not modify these relationships. DISCUSSION: Differential UWMC burden, not differential UWMC-and-cognition associations, may drive clinical AD disparities between racialized groups. HIGHLIGHTS: Unhealthy white matter connectivity (UWMC) in Alzheimer's disease (AD) pathology-affected brain regions is associated with cognition. Relationships between UWMC and cognition are similar between Black American (BA) and non-Hispanic White (nHW) individuals. More UWMC may partially drive higher clinical AD burden in BA versus nHW populations. UWMC risk factors, particularly social and environmental, should be identified.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Substância Branca/metabolismo , Doença de Alzheimer/complicações , Imageamento por Ressonância Magnética , Cognição , Encéfalo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/complicaçõesRESUMO
INTRODUCTION: Despite representing an essential workforce, it is unclear how global policy efforts target early-career dementia researchers (ECDRs). Thus, this study aimed to provide an overview of policies through which ECDRs are considered and supported by dementia plans and organizations. METHODS: G20 member states were evaluated for their national dementia plan alongside policies of leading dementia organizations. Data targeting support for ECDRs were extracted and subject to content analysis using inductive coding. Findings were categorized and narratively synthesized. RESULTS: Only China, Denmark, England, Greece, Northern Ireland, Scotland, Spain, and the United States mentioned ECDRs in their national plan. Additionally, 17 countries formalized ECDR support via dementia organizations. Support efforts included research funding, dissemination and networking, career development, and research advice. DISCUSSION: Few nations formally recognized ECDRs in dementia plans or through dementia organizations. To facilitate equal prospects for ECDRs, top-down approaches are urged to enhance and align their efforts. HIGHLIGHTS: Few G20 countries (8/46) had national dementia plans for early-career researchers. Targeted support comes from government and nongovernmental dementia organizations. Support includes funding, training, advice, research dissemination, and networking. Inconsistent definitions and eligibility criteria are barriers to accessing support. Global coordination and top-down policy will aid early-career dementia researchers.
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Demência , Pesquisadores , Humanos , Demência/terapia , Pesquisa Biomédica , Política de SaúdeRESUMO
Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.
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Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Masculino , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/diagnóstico , Fatores de RiscoRESUMO
INTRODUCTION: A body of literature reported associations between late-life general adiposity measures (eg, body mass index) and dementia. Little is known about the association of late-life body composition with dementia risk. METHODS: We determined this association among cognitively normal participants from the Cardiovascular Health Study- Cognition Study. Body composition was assessed by dual-energy x-ray absorptiometry in 1994-1995. Dementia was ascertained at annual follow-up from 1998-1999 to 2013. Associations of body composition with incident dementia were assessed by the Fine-Gray model. RESULT: Among 344 participants (mean age 78, 62.2% women), body composition was significantly different between men and women, despite similar body mass indexes (BMIs). Increased dementia risk was significantly associated with lower lean mass in men and marginally with low appendicular lean mass in women. DISCUSSION: Decreased lean mass was an indicator of increased dementia risk in older adults. Studies should test whether preventing lean mass loss in older adults reduces dementia risk.
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Composição Corporal , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Fatores de RiscoRESUMO
OBJECTIVES: To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia. DESIGN: Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect. SETTING: Economically depressed small-town population. PARTICIPANTS: Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white). RESULTS: Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model). CONCLUSIONS: Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.
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Disfunção Cognitiva/complicações , Demência/epidemiologia , Insuficiência Cardíaca/complicações , Hipertensão/complicações , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Apolipoproteína E4/genética , Disfunção Cognitiva/epidemiologia , Demência/genética , Exercício Físico , Feminino , Insuficiência Cardíaca/epidemiologia , Heterozigoto , Humanos , Hipertensão/epidemiologia , Masculino , Pennsylvania/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.
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Envelhecimento , Pesquisa Biomédica/métodos , Artérias Cerebrais , Doenças de Pequenos Vasos Cerebrais , Microvasos , Neurociências/métodos , Vigilância da População/métodos , Fatores Etários , Animais , Biomarcadores/metabolismo , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Circulação Cerebrovascular , Humanos , Microcirculação , Microvasos/diagnóstico por imagem , Microvasos/fisiopatologia , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: physical function (PF) and physical activity (PA) both decline as adults age and have been linked to negative outcomes, including dementia, depression and cardiovascular diseases. Although declines in each are associated with numerous negative outcomes, the longitudinal relationship between these two measures is unclear. OBJECTIVE: to examine the dynamic, bidirectional associations between declines in PF and PA. DESIGN: prospective cohort. SETTING: the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. SUBJECTS: about 1,404 men and women, 76.96 ± 7.2 years, 62.4% female and 95.2% white. METHODS: over nine annual assessment cycles, PF was evaluated via the timed Up-and-Go task and PA via a self-reported questionnaire. Piecewise latent growth models examined bidirectional associations between PA and PF to determine whether the initial values (intercept) or early slope (cycles 1-5) (in either PF or PA) predicted later slope (cycles 5-9) (in either PF or PA). RESULTS: initial PF significantly predicted early (standardised ß= -0.10, P < 0.001) and later (standardised ß= -0.09, P = 0.01) PA slopes. Initial PA significantly predicted later (standardised ß = -0.09, P = 0.04) but not early PF slope. Associations were independent of baseline memory test scores, baseline cognitive status, later cognitive status and age. Early physical function slope neither predicts later PA slope nor did early PA slope predict later PF slope (both P values >0.10). CONCLUSIONS: the relationship between PF and PA is bidirectional, with PF more consistently predicting declines of PA, both in the short- and long-term. Intervening on PF impairments may improve PA engagement, which could in turn promote PF and translate to beneficial effects on cognitive function, cardiovascular health and mood.
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Envelhecimento , Exercício Físico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Cognição , Feminino , Avaliação Geriátrica/métodos , Humanos , Estudos Longitudinais , Masculino , Memória , Pennsylvania , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known. HYPOTHESIS: A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia. METHODS: Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, N = 10, age: 74.9 years, 7 women) or health education (HE, N = 16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus, and cornu ammonis were measured at baseline and at 24-month follow-up using 7-Tesla magnetic resonance imaging. Between-group volumetric differences at 24 months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities, and brain atrophy. RESULTS: Between-group differences were significant for left hippocampus, left cornu ammonis, and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically nonsignificant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors. CONCLUSIONS: In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults.
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Terapia por Exercício/métodos , Exercício Físico/fisiologia , Hipocampo/diagnóstico por imagem , Comportamento Sedentário , Idoso , Idoso de 80 Anos ou mais , Feminino , Educação em Saúde/métodos , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores de TempoRESUMO
In this chapter, we consider lack of racial, ethnic, and geographic diversity in research studies from a public health perspective in which representation of a target population is critical. We review the state of the research field with respect to racial, ethnic, and geographic diversity in study participants. We next focus on key factors which can arise from the lack of diversity and can negatively impact external validity. Finally, we argue that the public's health, and future research, will ultimately be served by approaches from both recruitment and representation science and population neuroscience, and we close with recommendations from these two fields to improve diversity in studies.
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Background: Tau accumulation in Alzheimer's disease is associated with short term clinical progression and faster rates of cognitive decline in individuals with high amyloid-ß deposition. Defining an optimal threshold of tau accumulation predictive of cognitive decline remains a challenge. Objective: We tested the ability of regional tau PET sensitivity and specificity thresholds to predict longitudinal cognitive decline. We also tested the predictive performance of thresholds in the proposed new NIA-AA biological staging for Alzheimer's disease where multiple levels of tau positivity are used to stage participants. Methods: 18F-flortaucipir scans from 301 non-demented participants were processed and sampled. Four cognitive measures were assessed longitudinally. Regional standardized uptake value ratios were split into infra- and suprathreshold groups at baseline using previously derived thresholds. Survival analysis, log rank testing, and Generalized Estimation Equations assessed the relationship between the application of regional sensitivity/specificity thresholds and change in cognitive measures as well as tau threshold performance in predicting cognitive decline within the new NIA-AA biological staging. Results: The meta temporal region was best for predicting risk of short-term cognitive decline in suprathreshold, as compared to infrathreshold participants. When applying multiple levels of tau positivity, each subsequent level of tau identified cognitive decline at earlier timepoints. Conclusions: When using 18F-flortaucipir, meta temporal suprathreshold classification was associated with increased risk of cognitive decline, suggesting that abnormal tau deposition in the cortex predicts decline. Likewise, the application of multiple levels of tau clearly predicts the distinctive cognitive trajectories in the new NIA-AA biological staging framework.
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Disfunção Cognitiva , Tomografia por Emissão de Pósitrons , Proteínas tau , Humanos , Proteínas tau/metabolismo , Feminino , Masculino , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Carbolinas , Progressão da Doença , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Estudos Longitudinais , Testes Neuropsicológicos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso de 80 Anos ou mais , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Older adults with discordant biological and chronological ages (BA and CA) may vary in cognitive and physical function from those with concordant BA and CA. METHODS: To make our approach clinically accessible, we created easy-to-interpret participant groups in the Health, Aging, and Body Composition Study (Nâ =â 2 458, 52% female participants, 65% White participants, age: 73.5â ±â 2.8) based on medians of CA, and a previously validated BA index comprised of readily available clinical tests. Joint models estimated associations of BA-CA group with cognition (Modified Mini-Mental State Examination [3MS] and Digit Symbol Substitution Test [DSST]) and frailty over 10 years. RESULTS: The sample included the following: 32%, Young group (BA and CAâ <â median); 21%, Prematurely Aging group (BAâ ≥â median, CAâ <â median), 27%, Old group (BA and CAâ ≥â median), and 20%, Resilient group (BAâ <â median, CAâ ≥â median). In education-adjusted models of cognition, among those with CAâ <â median, the Prematurely Aging group performed worse than the Young at baseline (3MS and DSST pâ <â .0001), but among those with CAâ ≥â median, the Resilient group did not outperform the Old group (3MS pâ =â .31; DSST pâ =â .25). For frailty, the Prematurely Aging group performed worse than the Young group at baseline (pâ =â .0001), and the Resilient group outperformed the Old group (pâ =â .003). For all outcomes, groups did not differ on change over time based on the same pairwise comparisons (pâ ≥â .40). CONCLUSIONS: Discordant BA and CA identify groups who have greater cognitive and physical functional decline or are more protected than their CA would suggest. This information can be used for risk stratification.
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Disfunção Cognitiva , Fragilidade , Humanos , Feminino , Idoso , Masculino , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Cognição , Envelhecimento/psicologiaRESUMO
BACKGROUND: Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta-analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D). METHODS: Electronic databases were searched up to March 11, 2022 to include observational studies that examined the association between DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in people with T2D. We conducted a random-effects meta-analysis to calculate the relative risk (RR) with 95% confidence interval (CI) for each class of newer GLD. RESULTS: Ten studies (from nine articles) involving 819,511 individuals with T2D were included. Three studies found that SGLT2 inhibitor users had a lower risk of all-cause dementia than non-SGLT2 inhibitor users (RR, 0.62; 95% CI, 0.39-0.97). Five studies found that users versus nonusers of GLP-1RAs were associated with a significant reduction in the risk of all-cause dementia (RR, 0.72; 95% CI, 0.54-0.97). However, a meta-analysis for AD and VD was unavailable for SGLT2 inhibitors and GLP-1RAs because only one study was included for each drug. In seven studies, users vs. nonusers of DPP-4 inhibitors were significantly associated with a decreased risk of all-cause dementia (RR, 0.84; 95% CI, 0.74-0.94) and VD (RR, 0.59; 95% CI, 0.47-0.75) but not AD (RR, 0.82; 95% CI, 0.63-1.08). CONCLUSION: Newer GLDs were associated with a decreased risk of all-cause dementia in people with T2D. Because of the observational nature and significant heterogeneity between studies, the results should be interpreted with caution. Further research is warranted to confirm our findings.
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Demência , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Glucose , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Demência/prevenção & controle , Demência/complicaçõesRESUMO
A methodology for determining tau PET thresholds is needed to confidently detect early tau deposition. We compared multiple threshold-determining methods in participants who underwent either 18F-flortaucipir or 18F-MK-6240 PET scans. Methods: 18F-flortaucipir (n = 798) and 18F-MK-6240 (n = 216) scans were processed and sampled to obtain regional SUV ratios. Subsamples of the cohorts were based on participant diagnosis, age, amyloid-ß status (positive or negative), and neurodegeneration status (positive or negative), creating older-adult (age ≥ 55 y) cognitively unimpaired (amyloid-ß-negative, neurodegeneration-negative) and cognitively impaired (mild cognitive impairment/Alzheimer disease, amyloid-ß-positive, neurodegeneration-positive) groups, and then were further subsampled via matching to reduce significant differences in diagnostic prevalence, age, and Mini-Mental State Examination score. We used the biostatistical estimation of tau threshold hallmarks (BETTH) algorithm to determine sensitivity and specificity in 6 composite regions. Results: Parametric double receiver operating characteristic analysis yielded the greatest joint sensitivity in 5 of the 6 regions, whereas hierarchic clustering, gaussian mixture modeling, and k-means clustering all yielded perfect joint specificity (2.00) in all regions. Conclusion: When 18F-flortaucipir and 18F-MK-6240 are used, Alzheimer disease-related tau status is best assessed using 2 thresholds, a sensitivity one based on parametric double receiver operating characteristic analysis and a specificity one based on gaussian mixture modeling, delimiting an uncertainty zone indicating participants who may require further evaluation.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Carbolinas , Disfunção Cognitiva/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Proteínas tau/metabolismo , Pessoa de Meia-IdadeRESUMO
Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored. Methods: Using the Utah Population Database, we performed an 80-year retrospective cohort study of 59,668 parous women. Results: Women with, versus without, HDP, had a 1.37 higher risk of all-cause dementia (95% confidence interval [CI]: 1.26, 1.50) after adjustment for maternal age at index birth, birth year, and parity. HDP was associated with a 1.64 higher risk of vascular dementia (95% CI: 1.19, 2.26) and 1.49 higher risk of other dementia (95% CI: 1.34, 1.65) but not Alzheimer's disease dementia (adjusted hazard ratio = 1.04; 95% CI: 0.87, 1.24). Gestational hypertension and preeclampsia/eclampsia showed similar increased dementia risk. Nine mid-life cardiometabolic and mental health conditions explained 61% of HDP's effect on subsequent dementia risk. Discussion: Improved HDP and mid-life care could reduce the risk of dementia.
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A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.
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Disfunção Cognitiva , Demência , Hipertensão , Humanos , Idoso , Idoso de 80 Anos ou mais , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Disfunção Cognitiva/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Demência/prevenção & controle , InternacionalidadeRESUMO
INTRODUCTION: The World Health Organization recognizes dementia as a public health priority and highlights research as an action to respond to the consequences, with early career dementia researchers (ECDRs) representing the key driving force. Due to the COVID-19 pandemic, however, biomedical and psychosocial dementia research was strained worldwide. The aim of this study was to understand the impact of the pandemic on ECDRs. METHODS: In autumn 2021, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Professional Interest Area to Elevate Early Career Researchers (PEERs) and University College London conducted an online survey querying ECDRs' experiences during the COVID-19 pandemic. The survey was shared through the ISTAART network, social media, podcasts, and emailing lists. Data were analyzed using descriptive and inferential statistics. RESULTS: Survey data from n = 321 ECDRs from 34 countries were analyzed (67.6% women; 78.8% working in academia). Overall, 77.8% of ECDRs surveyed indicated research delays, 53.9% made project adjustments, 37.9% required additional or extended funding, and 41.8% reported a negative impact on career progression. Moreover, 19.9% felt unsupported by their institutions and employers (33% felt well supported, 42.7% somewhat supported). ECDR's conference attendance remained the same (26.5%) or increased (More: 28.6%; a lot more: 5.6%) since the start of the pandemic. Continental differences were visible, while the impact of the pandemic did not differ greatly based on ECDRs' sociodemographic characteristics. CONCLUSIONS: The COVID-19 pandemic had a substantial impact on ECDRs worldwide and institutions, employers, and funding bodies are urged to consider the implications and lessons-learned when working with, managing, and promoting ECDRs. Strategies related to the pandemic and general career support to improve ECDRs career progression are discussed, including social media training, digital networking, and benefits of hybrid events. Global resources specific for ECDRs are highlighted.