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1.
Ageing Res Rev ; 101: 102507, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39306249

RESUMO

Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer's disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia. We found no strong evidence of racial and ethnic differences in imaging biomarkers after controlling for cognitive status and cardiovascular risks. For biofluid biomarkers, in AA, higher levels of plasma Aß42/Aß40, and lower levels of CSF total tau and p-tau 181, were observed after controlling for APOE status and comorbidities compared to NHW. Examining the impact of AD risks and comorbidities on biomarkers and their contributions to racial/ethnic differences in cognitive impairment are critical to interpreting biomarkers, understanding their generalizability, and eliminating racial/ethnic health disparities.

2.
Alzheimers Dement (Amst) ; 16(3): e12632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39130803

RESUMO

INTRODUCTION: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers. METHODS: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal (n = 76), had impaired cognition without mild cognitive impairment (MCI) (n = 41), or carried a diagnosis of MCI (n = 253) or dementia (n = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers. RESULTS: MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups. DISCUSSION: Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed. Highlights: The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers.Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non-Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only.These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics.

3.
JAMA Netw Open ; 7(8): e2427073, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39120898

RESUMO

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.


Assuntos
Doença de Alzheimer , Negro ou Afro-Americano , Hispânico ou Latino , Humanos , Doença de Alzheimer/etnologia , Idoso , Feminino , Masculino , Estudos Transversais , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Hispânico ou Latino/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Seleção de Pacientes , Estados Unidos , Estudos Longitudinais , Disfunção Cognitiva
4.
Alzheimers Dement (Amst) ; 16(3): e12617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021585

RESUMO

INTRODUCTION: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples. METHODS: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aß-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aß-PET. RESULTS: A total of 239 participants underwent blood draw and Aß-PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p-tau217 showed excellent discrimination of Aß-PET positive and negative participants (visual read: AUC = 0.91 [0.87-0.95], p < 0.001; Centiloids quantification: AUC = 0.90 [0.86-0.94]). There was a greater percent agreement between low p-tau217 and negative Aß-PET (95.8%) than high p-tau217 and positive Aß-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance. DISCUSSION: Plasma p-tau217 (ALZPath) relates to brain Aß in Hispanic/Latino and non-Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno-racially diverse populations. HIGHLIGHTS: Plasma p-tau217 (ALZPath) and Aß-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aß-PET positive and negative participants.Applying a two-cutoff "intermediate" plasma p-tau217 approach could reduce need for more invasive and costly testing.Plasma p-tau217 associations with Aß-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups.

5.
JAMA Neurol ; 81(6): 619-629, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38619853

RESUMO

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.


Assuntos
Doença de Alzheimer , Imageamento por Ressonância Magnética , Neuroglia , Tomografia por Emissão de Pósitrons , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neuroglia/patologia , Neuroglia/metabolismo , Estudos Transversais , Estudos Retrospectivos , Emaranhados Neurofibrilares/patologia , Proteínas tau/metabolismo , Pessoa de Meia-Idade , Neuroimagem , Estudos de Coortes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , Autopsia
6.
Diagnostics (Basel) ; 14(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611617

RESUMO

An improved understanding of the pathobiology of Alzheimer's disease (AD) should lead ultimately to an earlier and more accurate diagnosis of AD, providing the opportunity to intervene earlier in the disease process and to improve outcomes. The known hallmarks of Alzheimer's disease include amyloid-ß plaques and neurofibrillary tau tangles. It is now clear that an imbalance between production and clearance of the amyloid beta protein and related Aß peptides, especially Aß42, is a very early, initiating factor in Alzheimer's disease (AD) pathogenesis, leading to aggregates of hyperphosphorylation and misfolded tau protein, inflammation, and neurodegeneration. In this article, we review how the AD diagnostic process has been transformed in recent decades by our ability to measure these various elements of the pathological cascade through the use of imaging and fluid biomarkers. The more recently developed plasma biomarkers, especially phosphorylated-tau217 (p-tau217), have utility for screening and diagnosis of the earliest stages of AD. These biomarkers can also be used to measure target engagement by disease-modifying therapies and the response to treatment.

7.
Front Neurol ; 15: 1364658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595851

RESUMO

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

8.
Alzheimers Dement ; 20(4): 2830-2842, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38441274

RESUMO

INTRODUCTION: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-ß (Aß42/40) positivity in Aß positron emission tomography (PET) negative individuals. METHODS: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aß plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS: Plasma+/PET- demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma-/PET-. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET-. Composite brain FW correlated with plasma Aß42/40 and p-tau181. DISCUSSION: FW imaging changes distinguish plasma Aß42/40 positive and negative groups, independent of group differences in cognitive status, Aß PET status, and other plasma biomarkers (i.e., t-tau, p-tau181, glial fibrillary acidic protein, neurofilament light). HIGHLIGHTS: Plasma Aß42/40 positivity is associated with brain microstructure decline. Plasma+/PET- demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET- demonstrated decreased FAt in 66 total GM and WM regions. Whole-brain FW correlated with plasma Aß42/40 and p-tau181 measures. Plasma+/PET- demonstrated decreased cortical volume and thickness.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Disfunção Cognitiva/metabolismo , Imagem de Difusão por Ressonância Magnética , Biomarcadores , Proteínas tau
9.
Front Aging Neurosci ; 16: 1336008, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357533

RESUMO

Introduction: This study investigated the role of proactive semantic interference (frPSI) in predicting the progression of amnestic Mild Cognitive Impairment (aMCI) to dementia, taking into account various cognitive and biological factors. Methods: The research involved 89 older adults with aMCI who underwent baseline assessments, including amyloid PET and MRI scans, and were followed longitudinally over a period ranging from 12 to 55 months (average 26.05 months). Results: The findings revealed that more than 30% of the participants diagnosed with aMCI progressed to dementia during the observation period. Using Cox Proportional Hazards modeling and adjusting for demographic factors, global cognitive function, hippocampal volume, and amyloid positivity, two distinct aspects of frPSI were identified as significant predictors of a faster decline to dementia. These aspects were fewer correct responses on a frPSI trial and a higher number of semantic intrusion errors on the same trial, with 29.5% and 31.6 % increases in the likelihood of more rapid progression to dementia, respectively. Discussion: These findings after adjustment for demographic and biological markers of Alzheimer's Disease, suggest that assessing frPSI may offer valuable insights into the risk of dementia progression in individuals with aMCI.

10.
Alzheimers Dement ; 20(1): 437-446, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37671801

RESUMO

INTRODUCTION: Alzheimer's disease studies often lack ethnic diversity. METHODS: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aß-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry. RESULTS: Three-hundred seventy nine participants underwent blood draw (71.9 ± 7.8 years old, 60.2% female, 57% Hispanic of which 88% were Cuban or South American) and 240 completed Aß-PET. P-tau181 was higher in amnestic MCI (p = 0.004, d = 0.53) and dementia (p < 0.001, d = 0.97) than in clinically normal participants and discriminated Aß-PET[+] and Aß-PET[-] (AUC = 0.86). P-tau181 outperformed GFAP and NfL. There were no significant interactions with ethnicity. Among amnestic MCI, Hispanics had lower odds of elevated p-tau181 than non-Hispanic (OR = 0.41, p = 0.006). DISCUSSION: Plasma p-tau181 informs etiological diagnosis of cognitively impaired Hispanic and non-Hispanic older adults. Hispanic ethnicity may relate to greater likelihood of non-Alzheimer's contributions to memory loss. HIGHLIGHTS: Alzheimer's biomarkers were measured in Hispanic and non-Hispanic older adults. Plasma p-tau181 related to amnestic cognitive decline and brain amyloid burden. AD biomarker associations did not differ between Hispanic and non-Hispanic ethnicity. Hispanic individuals may be more likely to have non-Alzheimer causes of memory loss.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Masculino , Proteínas Amiloidogênicas , Encéfalo/diagnóstico por imagem , Amnésia , Biomarcadores , Peptídeos beta-Amiloides , Proteínas tau
11.
Gerontology ; 70(1): 48-58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37903474

RESUMO

INTRODUCTION: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1-2 present), or frail (3-4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. RESULTS: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, ß^ = -0.61, 95% CI: -0.83, -0.38 and ß^ = -0.21, 95% CI: -0.30, -0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. DISCUSSION/CONCLUSION: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.


Assuntos
Disfunção Cognitiva , Fragilidade , Idoso , Humanos , Idoso de 80 Anos ou mais , Fragilidade/diagnóstico , Idoso Fragilizado , Estudos Transversais , Inquéritos Nutricionais , Avaliação Geriátrica , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Cognição
12.
Brain Imaging Behav ; 18(1): 106-116, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37903991

RESUMO

Prior evidence suggests that Hispanic and non-Hispanic individuals differ in potential risk factors for the development of dementia. Here we determine whether specific brain regions are associated with cognitive performance for either ethnicity along various stages of Alzheimer's disease. For this cross-sectional study, we examined 108 participants (61 Hispanic vs. 47 Non-Hispanic individuals) from the 1Florida Alzheimer's Disease Research Center (1Florida ADRC), who were evaluated at baseline with diffusion-weighted and T1-weighted imaging, and positron emission tomography (PET) amyloid imaging. We used FreeSurfer to segment 34 cortical regions of interest. Baseline Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used as measures of cognitive performance. Group analyses assessed free-water measures (FW) and volume. Statistically significant FW regions based on ethnicity x group interactions were used in a stepwise regression function to predict total MMSE and MoCA scores. Random forest models were used to identify the most predictive brain-based measures of a dementia diagnosis separately for Hispanic and non-Hispanic groups. Results indicated elevated FW values for the left inferior temporal gyrus, left middle temporal gyrus, left banks of the superior temporal sulcus, left supramarginal gyrus, right amygdala, and right entorhinal cortex in Hispanic AD subjects compared to non-Hispanic AD subjects. These alterations occurred in the absence of different volumes of these regions in the two AD groups. FW may be useful in detecting individual differences potentially reflective of varying etiology that can influence cognitive decline and identify MRI predictors of cognitive performance, particularly among Hispanics.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Estudos Transversais , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Água
13.
J Int Neuropsychol Soc ; 30(2): 128-137, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37385978

RESUMO

OBJECTIVE: To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI). METHOD: One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement. RESULTS: Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (ß = .000464, R2 = .196, p < .01) and the WNH group (ß = .000455, R2 = .195, p < .05). Education (ß = .000028, R2 = .168, p < .01) and sex (ß = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs. CONCLUSIONS: Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.


Assuntos
Apolipoproteína E4 , Feminino , Humanos , Masculino , Apolipoproteína E4/genética , Biomarcadores , Demografia , Córtex Entorrinal/diagnóstico por imagem , Doenças Neurodegenerativas
14.
Arch Clin Neuropsychol ; 39(4): 464-481, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38123477

RESUMO

OBJECTIVE: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39). METHOD: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups. RESULTS: A total of 8 items were differentially difficult between languages in the 32-item version of the MINT. EA scored significantly higher than HA, but the difference was not significant when removing those 8 items (controlling for Education). The Receiver Operating Characteristics showed that the MINT had poor accuracy when identifying CN participants and was acceptable in identifying dementia participants but unacceptable in classifying MCI participants. Finally, we tested the association between MINT scores and magnetic resonance imaging volumetric measures of language-related areas in the temporal and frontal lobes. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral middle temporal gyrus. The left fusiform gyrus correlated with MINT scores regardless of language and MINT version. We also found differential correlations depending on the language of administration. CONCLUSIONS: Our results highlight the importance of analyzing cross-cultural samples when implementing clinical neuropsychological tests such as the MINT.


Assuntos
Disfunção Cognitiva , Comparação Transcultural , Demência , Multilinguismo , Testes Neuropsicológicos , Psicometria , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etnologia , Demência/diagnóstico , Demência/etnologia , Hispânico ou Latino , Imageamento por Ressonância Magnética/normas , Testes Neuropsicológicos/normas , Testes Neuropsicológicos/estatística & dados numéricos , Psicometria/normas , Psicometria/instrumentação , Reprodutibilidade dos Testes , Curva ROC , População Branca
15.
Alzheimers Dement ; 19 Suppl 9: S74-S88, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37850549

RESUMO

INTRODUCTION: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. DISCUSSION: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. HIGHLIGHTS: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/patologia , Reprodutibilidade dos Testes , Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodos , Atrofia/patologia , Biomarcadores
16.
Alzheimers Dement ; 19 Suppl 9: S64-S73, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37801072

RESUMO

INTRODUCTION: One goal of the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40-64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants. METHODS: LEADS amyloid-positive early-onset Alzheimer's disease (EOAD) or negative early-onset non-AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar-age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study. RESULTS: Previously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases. DISCUSSION: Results suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases. HIGHLIGHTS: Sequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a key resource for early-onset Alzheimer's genetic research.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Proteína C9orf72/genética , Testes Genéticos , Estudos Longitudinais , Mutação , Presenilina-1/genética , Presenilina-2/genética
17.
Alzheimers Dement ; 19 Suppl 9: S98-S114, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37690109

RESUMO

INTRODUCTION: We aimed to describe baseline amyloid-beta (Aß) and tau-positron emission tomograrphy (PET) from Longitudinal Early-onset Alzheimer's Disease Study (LEADS), a prospective multi-site observational study of sporadic early-onset Alzheimer's disease (EOAD). METHODS: We analyzed baseline [18F]Florbetaben (Aß) and [18F]Flortaucipir (tau)-PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aß+) from EOnonAD (Aß-) based on the combination of visual read by expert reader and image quantification. RESULTS: 243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid-PET; 231 (95.1%) of them were tau-PET positive (A+T+). Tau-PET signal was elevated across cortical regions with a parietal-predominant pattern, and higher burden was observed in younger and female EOAD participants. DISCUSSION: LEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau-PET binding at baseline might have implications for therapeutic strategies in patients with EOAD. HIGHLIGHTS: 72% of patients with clinical EOAD were positive on both amyloid- and tau-PET. Amyloid-positive patients with EOAD had high tau-PET signal across cortical regions. In EOAD, tau-PET mediated the relationship between amyloid-PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau-PET.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Feminino , Doença de Alzheimer/metabolismo , Elétrons , Estudos Prospectivos , Proteínas tau/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Amiloide/metabolismo , Biomarcadores
18.
Alzheimers Dement ; 19 Suppl 9: S29-S41, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37653686

RESUMO

INTRODUCTION: The Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early-onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD. METHODS: We transcribed RAVLT recordings from 303 subjects in the Longitudinal Early-Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J-curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables. RESULTS: Compared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter-syndromic differences were noted with raw score, primacy, recency, J-curve, and stopping time. DISCUSSION: RAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores. HIGHLIGHTS: RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing-based scores add value over traditional count-based scores.


Assuntos
Doença de Alzheimer , Memória Episódica , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Testes Neuropsicológicos , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Estudos Longitudinais , Proteínas Amiloidogênicas
19.
Neurology ; 101(14): e1412-e1423, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37580158

RESUMO

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) is neuropathologically classified into 3 corticolimbic subtypes based on the neurofibrillary tangle distribution throughout the hippocampus and association cortices: limbic predominant, typical, and hippocampal sparing. In vivo, a fourth subtype, dubbed "minimal atrophy," was identified using structural MRI. The objective of this study was to identify a neuropathologic proxy for the neuroimaging-defined minimal atrophy subtype. METHODS: We applied 2 strategies in the Florida Autopsied Multi-Ethnic (FLAME) cohort to evaluate a neuropathologic proxy for the minimal atrophy subtype. In the first strategy, we selected AD cases with a Braak tangle stage IV (Braak IV) because of the relative paucity of neocortical tangle involvement compared with Braak >IV. Braak IV cases were compared with the 3 AD subtypes. In the alternative strategy, typical AD was stratified by brain weight and cases having a relatively high brain weight (>75th percentile) were defined as minimal atrophy. RESULTS: Braak IV cases (n = 37) differed from AD subtypes (limbic predominant [n = 174], typical [n = 986], and hippocampal sparing [n = 187] AD) in having the least years of education (median 12 years, group-wise p < 0.001) and the highest brain weight (median 1,140 g, p = 0.002). Braak IV cases most resembled the limbic predominant cases owing to their high proportion of APOE ε4 carriers (75%, p < 0.001), an amnestic syndrome (100%, p < 0.001), as well as older age of cognitive symptom onset and death (median 79 and 85 years, respectively, p < 0.001). Only 5% of Braak IV cases had amygdala-predominant Lewy bodies (the lowest frequency observed, p = 0.017), whereas 32% had coexisting pathology of Lewy body disease, which was greater than the other subtypes (p = 0.005). Nearly half (47%) of the Braak IV samples had coexisting limbic predominant age-related TAR DNA-binding protein 43 encephalopathy neuropathologic change. Cases with a high brain weight (n = 201) were less likely to have amygdala-predominant Lewy bodies (14%, p = 0.006) and most likely to have Lewy body disease (31%, p = 0.042) compared with those with middle (n = 455) and low (n = 203) brain weight. DISCUSSION: The frequency of Lewy body disease was increased in both neuropathologic proxies of the minimal atrophy subtype. We hypothesize that Lewy body disease may underlie cognitive decline observed in minimal atrophy cases.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/patologia , Estudos Retrospectivos , Doença por Corpos de Lewy/patologia , Emaranhados Neurofibrilares/patologia , Encéfalo/patologia , Atrofia/patologia
20.
Front Neurol ; 14: 1179205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602238

RESUMO

Introduction: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A-) on positron emission tomography (PET). Method: This study examines the association between SI and plasma - based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-ß peptide fragments (Aß42/Aß40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging. Results: The aMCI A+ (n = 42) group had a higher percentage of ApoE ɛ4 carriers, and greater levels of pTau-181 and SI, than Cognitively Unimpaired (CU) A- participants (n = 25). CU controls did not differ from aMCI A- (n = 61) on plasma biomarkers or ApoE genotype. Logistic regression indicated that ApoE ɛ4 positivity, pTau-181, and SI were independent differentiating predictors (Correct classification = 82.0%; Sensitivity = 71.4%; Specificity = 90.2%) in identifying A+ from A- aMCI cases. Discussion: A combination of plasma biomarkers, ApoE positivity and SI had high specificity in identifying A+ from A- aMCI cases.

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