Sex Differences in in vivo Alzheimer’s Disease Neuropathology in Late Middle-Aged Hispanics

Luchsinger, José A.; Palta, Priya; Rippon, Brady; Soto, Luisa M. Solis; Ceballos, Fernando; Pardo, Michelle; Laing, Krystal K; Igwe, Kay C.; Johnson, Aubrey S.; Tomljanovic, Zeljko; He, Hengda; Reitz, Christiane; Kreisl, William Charles; Razlighi, Qolamreza R.; Teresi, Jeanne A.; Moreno, Herman; Brickman, Adam M.

doi:10.3233/jad-191183

Cited by 13 publications

(9 citation statements)

References 35 publications

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“… 63 However, sex differences in amyloid pathology in elderly individuals are controversial. Worse amyloid PET pathology was reported in men in cohorts 70 to 85 years old, 64 while in cohorts of ∼64‐year‐olds 65 and 40‐ to 60‐year‐olds, 66 women exhibited worse amyloid pathology, particularly during menopause transition. It is tempting to speculate that sexual dimorphism in amyloid pathology may vary depending on age.…”

Section: Discussionmentioning

confidence: 94%

Sex‐dependent cholinergic effects on amyloid pathology: A translational study

German‐Castelan,

Shanks,

Gros

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONAbout two‐thirds of Alzheimer's Disease (AD) patients are women, who exhibit more severe pathology and cognitive decline than men. Whether biological sex causally modulates the relationship between cholinergic signaling and amyloid pathology remains unknown.METHODSWe quantified amyloid beta (Aβ) in male and female App‐mutant mice with either decreased or increased cholinergic tone and examined the impact of ovariectomy and estradiol replacement in this relationship. We also investigated longitudinal changes in basal forebrain (cholinergic function) and Aβ in elderly individuals.RESULTSWe show a causal relationship between cholinergic tone and amyloid pathology in males and ovariectomized female mice, which is decoupled in ovary‐intact and ovariectomized females receiving estradiol. In elderly humans, cholinergic loss exacerbates Aβ.DISCUSSIONOur findings emphasize the importance of reflecting human menopause in mouse models. They also support a role for therapies targeting estradiol and cholinergic signaling to reduce Aβ.Highlights Cholinergic tone regulates amyloid beta (Aβ) pathology in males and ovariectomized female mice. Estradiol uncouples the relationship between cholinergic tone and Aβ. In elderly humans, cholinergic loss correlates with increased Aβ in both sexes.

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Section: Discussionmentioning

confidence: 94%

Sex‐dependent cholinergic effects on amyloid pathology: A translational study

German‐Castelan,

Shanks,

Gros

et al. 2023

Alzheimer's & Dementia

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“…The analysis of inequalities depending on sex aims to enrich the analysis and generates a more rigorous knowledge of reality. Already classic studies point to the need of contemplating the sex variable as an important modulating factor in both the encoding and decoding of emotions (Zuckerman et al, 1979) and, currently, this approach is identified as a growing field of scientific study (Abbruzzese et al, 2019;Luchsinger et al, 2020;Sullivan et al, 2017). Attending to brain dimorphism, it would be convenient to perform analyses of performance in experimental tasks including the variable "sex" (Pletzer, 2019).…”

Section: Discussionmentioning

confidence: 99%

Una revisión sistemática acerca del reconocimiento facial de las emociones en la Enfermedad de Alzheimer: una perspectiva evolutiva y de género

et al. 2021

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La correcta identificación de las emociones básicas (alegría, miedo, asco, tristeza, sorpresa e ira) desempeñan un importante papel en las relaciones sociales y conductas ligadas a la propia supervivencia. En la Enfermedad de Alzheimer (EA) la capacidad de reconocimiento emocional podría estar ya alterada en fases iniciales. Por ello, el objetivo principal del presente trabajo fue realizar una revisión sistemática de la literatura acerca del reconocimiento facial en personas con EA, identificando posibles variables moduladoras. Se realizó una búsqueda en las bases de datos Web of Science y PsycINFO. Después de aplicar los criterios de inclusión-exclusión se seleccionaron un total de 28 artículos. Las imágenes estáticas fueron los estímulos más utilizados para evaluar el reconocimiento de las emociones básicas, especialmente las fotografías desarrolladas por Paul Ekman y colaboradores. Los resultados de la revisión indican que en las personas con EA generalmente muestran déficit del reconocimiento emocional aunque los datos no son concluyentes, lo que podría estar relacionado con la diversidad de metodologías aplicadas. En relación con las variables evaluadas (sexo y edad) se pone de manifiesto la necesidad de futuras investigaciones que estudien de forma sistemática cómo estos factores pueden modular el reconocimiento emocional en pacientes con Enfermedad de Alzheimer. The correct identification of basic emotions (joy, fear, disgust, sadness, surprise and anger) plays an important role in social relationships and behaviors linked to one´s survival. In Alzheimer´s disease (AD) the ability to recognize emotions may already be impaired at early stages of the disease. Therefore, the main objective of the present study was to carry out a systematic review of the literature on facial emotional recognition in people with AD, identifying possible modulating variables. A search in the Web of Science and PsycInfo databases was carried out. After applying the inclusion-exclusion criteria, a total of 28 articles were selected. Static images were the most used stimuli to evaluate the recognition of basic emotions, especially the photographs developed by Paul Ekman and collaborators. Results of the present review indicate the people with AD generally display deficits in emotional recognition although the data are not conclusive, which could be related to the diversity of methodologies applied. In relation to the variables evaluated (sex and age) the need of further research in order to study how these factors could modulate emotional recognition in patients with Alzheimer´s disease is highlighted.

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“…MK‐6240 PET scans (n = 320) were gathered from participants in various ongoing studies at Columbia University Irving Medical Center (CUIMC). These include the Washington Heights Inwood Columbia Aging Project 23 (n = 4), the Northern Manhattan Study of Metabolism and Mind (NOMEM) 24 (n = 200), the VALAD (Valacyclovir Treatment of Alzheimer's Disease) study 25 (n = 57), and other studies recruiting participants at CUMC 26 (n = 59). These studies—as well as the current study—were reviewed by the institutional review board, and all participating subjects gave consent for all procedures.…”

Section: Methodsmentioning

confidence: 99%

Deep learning improves utility of tau PET in the study of Alzheimer's disease

Zou¹,

Park²,

Johnson³

et al. 2021

Alz & Dem Diag Ass & Dis Mo

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Introduction Positron emission tomography (PET) imaging targeting neurofibrillary tau tangles is increasingly used in the study of Alzheimer's disease (AD), but its utility may be limited by conventional quantitative or qualitative evaluation techniques in earlier disease states. Convolutional neural networks (CNNs) are effective in learning spatial patterns for image classification. Methods 18F‐MK6240 (n = 320) and AV‐1451 (n = 446) PET images were pooled from multiple studies. We performed iterations with differing permutations of radioligands, heuristics, and architectures. Performance was compared to a standard region of interest (ROI)‐based approach on prediction of memory impairment. We visualized attention of the network to illustrate decision making. Results Overall, models had high accuracy (> 80%) with good average sensitivity and specificity (75% and 82%, respectively), and had comparable or higher accuracy to the ROI standard. Visualizations of model attention highlight known characteristics of tau radioligand binding. Discussion CNNs could improve tau PET's role in early disease and extend the utility of tau PET across generations of radioligands.

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Sex Differences in in vivo Alzheimer’s Disease Neuropathology in Late Middle-Aged Hispanics

Cited by 13 publications

References 35 publications

Sex‐dependent cholinergic effects on amyloid pathology: A translational study

Sex‐dependent cholinergic effects on amyloid pathology: A translational study

Una revisión sistemática acerca del reconocimiento facial de las emociones en la Enfermedad de Alzheimer: una perspectiva evolutiva y de género

Deep learning improves utility of tau PET in the study of Alzheimer's disease

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