Sex and gender differences in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis: A narrative review

Baschi, Roberta; Cicero, Calogero Edoardo; Iacono, Salvatore; Re, Vincenzina Lo; Luca, Antonina; Schirò, Giuseppe; Monastero, Roberto

doi:10.1016/j.mad.2023.111821

Cited by 10 publications

(6 citation statements)

References 187 publications

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“…The term ALS is used as the overarching term for this set of disorders of motor neuron diseases. The reliability for identifying ALS diagnoses in the UK biobank has been well validated, and shows high positive predictive value estimates of 70% to 91% 22 …”

Section: Methodsmentioning

confidence: 99%

“…Time‐to‐event Cox proportional hazard analyses were performed using 2 models. The incidence of ALS varies based on both sex and age, 15,22,25,26 so it is possible that sex‐ and age‐specific immune responses may contribute to these demographic differences. Therefore, model 1 was adjusted for demographic variables (age and sex) and was chosen as the minimally adjusted model.…”

Section: Methodsmentioning

confidence: 99%

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Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI‐ and Age‐Dependent Manner

Cao

Tian

et al. 2023

Annals of Neurology

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ObjectivePeripheral immune markers have been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, whether dysregulation of peripheral immunity is a risk factor for ALS or a consequence of motor neuron degeneration has not yet been clarified. We aimed to identify longitudinal associations between prediagnostic peripheral immunity and the risk of incident ALS.MethodsA total of 345,000 individuals from the UK Biobank between 2006 and 2010 were included at the baseline. The counts of peripheral immune markers (neutrophils, lymphocytes, monocytes, platelets and CRP) and its derived metrics (NLR、PLR、SII、LMR) were analyzed in relation to the following incident ALS by Cox‐proportional hazard models. Subgroup and interaction analyses were performed to explore the covariates of these relationships further.ResultsAfter adjusting for all covariates, the multivariate analysis showed that high neutrophil counts and their derived metrics (NLR, SII) were associated with an increased risk of ALS incidence (per SD increment HR, 95% CI: 1.15, 1.02‐1.29 for neutrophils; 1.15, 1.03‐1.28 for NLR; and 1.17, 1.05‐1.30 for SII). Subgroup and interaction analyses revealed that BMI and age had specific effects on this association. In participants with BMI≥25 or age<65, higher neutrophil counts and their metrics increased the risk of incident ALS; however, in participants with BMI<25 or age≥65, neutrophils had no effect on incident ALS.InterpretationOur study provides evidence that increased neutrophil levels and neutrophil‐derived metrics (NLR and SII) are associated with an increased risk of developing ALS.This article is protected by copyright. All rights reserved.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI‐ and Age‐Dependent Manner

Cao

Tian

et al. 2023

Annals of Neurology

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“…Here, we aimed to statistically control for such factors while maximizing the sample size to increase statistical power. It must be noted, though, that, for example, gender effects may be worthwhile to investigate in more detail 71,72 . On the other hand, the sample was ethnically and socio-demographically rather homogenous, most likely owing to our recruiting strategy via memory clinics and newspaper advertisements.…”

Section: Discussionmentioning

confidence: 99%

Single-value fMRI scores reflect both stage and risk across the Alzheimer’s disease continuum

Soch,

Richter,

Kizilirmak

et al. 2023

Preprint

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Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD).To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants’ whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype.Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel.Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

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“…Variations in the mechanisms and pathways related to the pathophysiology of diseases have been observed between the two sexes, as well as in their clinical manifestation, prognosis, and outcomes. Accordingly, ongoing studies on such aspects of major diseases are being performed [58,63]. They can prove useful in establishing new criteria and guidelines for the two sexes, particularly women.…”

Section: Sex/gender Dimorphism: An Important Modifier Of Immune Syste...mentioning

confidence: 99%

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Balistreri,

Monastero

2023

Brain Sciences

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The term “neuroinflammation” defines the typical inflammatory response of the brain closely related to the onset of many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through many efforts and research. Consequently, new cellular and molecular mechanisms, diverse and conventional, are emerging. In listing some of those that will be the subject of our description and discussion, essential are the important roles of peripheral and infiltrated monocytes and clonotypic cells, alterations in the gut–brain axis, dysregulation of the apelinergic system, alterations in the endothelial glycocalyx of the endothelial component of neuronal vascular units, variations in expression of some genes and levels of the encoding molecules by the action of microRNAs (miRNAs), or other epigenetic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences, and modifications in the circadian cycle. Such mechanisms can add significantly to understanding the complex etiological puzzle of neuroinflammation and ND. In addition, they could represent biomarkers and targets of ND, which is increasing in the elderly.

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Sex and gender differences in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis: A narrative review

Cited by 10 publications

References 187 publications

Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI‐ and Age‐Dependent Manner

Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI‐ and Age‐Dependent Manner

Single-value fMRI scores reflect both stage and risk across the Alzheimer’s disease continuum

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

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