Sex ratio in dementia with Lewy bodies balanced between Alzheimer’s disease and Parkinson’s disease dementia: a cross-sectional study

Mouton, Aurélie; Blanc‬, ‪Frederic; Gros, Auriane; Manera, Valéria; Fabre, Roxane; Sauleau, Erik; Gomez-Luporsi, I.; Tifratene, Karim; Friedman, L.; Thümmler, Susanne; Pradier, Christian; Pierpoint, Robert; David, Romain

doi:10.1186/s13195-018-0417-4

Cited by 52 publications

(36 citation statements)

References 32 publications

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“…In addition to maltose, network analyses suggested a role for androgenic steroid metabolites in global cognition. Sex differences in cognitive function and certain neuropsychiatric diseases have been reported previously [19–21]. Consistent with findings reported here, sex hormones, including androgens, were believed to be important drivers underlying these associations [20,22].…”

Section: Discussionsupporting

confidence: 90%

Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants

Shi

Bazzano

et al. 2019

Aging

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Background: Metabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function. Methods: During 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex. Results: Five known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10 -5 ], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10 -5 ). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10 -6 ), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10 -5 ), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10 -5 ) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10 -4 and 3.00×10 -3 , respectively). Conclusion: The novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.

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Section: Discussionsupporting

confidence: 90%

Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants

Shi

Bazzano

et al. 2019

Aging

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“…In line with this hypothesis, a recent study reported a higher DLB prevalence of men than women under the age of 75 years, which equalized between the ages of 75 and 80 years. Above the age of 80 years, however, DLB was more common in women [8]. Future studies will have to demonstrate whether this shift in prevalence is mediated by hormonal differences.…”

Section: Discussionmentioning

confidence: 93%

“…Pathologically, DLB is characterized by the presence of cortical Lewy bodies, i.e., neuronal inclusions of alpha-synuclein proteins [2], frequently combined with Alzheimer's disease (AD) pathology, i.e., amyloid plaques and neurofibrillary tangles (NFT) [3]. Most studies report a higher prevalence of DLB in men than in women [4][5][6][7], although a few report the opposite [8,9]. In addition to the skewed distribution, there is evidence of differences in the underlying pathology between women and men with DLB.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies

et al. 2020

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Background: Dementia with Lewy bodies (DLB) is more prevalent in men than in women. In addition, postmortem studies found sex differences in underlying pathology. It remains unclear whether these differences are also present antemortem in in vivo biomarkers, and whether sex differences translate to variability in clinical manifestation. The objective of this study was to evaluate sex differences in cerebrospinal fluid (CSF) biomarker concentrations (i.e., alpha-synuclein (α-syn), amyloid β1-42 (Aβ42), total tau (Tau), phosphorylated tau at threonine 181 (pTau)) and clinical characteristics in DLB. Methods: We included 223 DLB patients from the Amsterdam Dementia Cohort, of which 39 were women (17%, age 70 ± 6, MMSE 21 ± 6) and 184 men (83%, age 68 ± 7, MMSE 23 ± 4). Sex differences in CSF biomarker concentrations (i.e., α-syn, Aβ42, Tau, and pTau) were evaluated using age-corrected general linear models (GLM). In addition, we analyzed sex differences in core clinical features (i.e., visual hallucinations, parkinsonism, cognitive fluctuations, and REM sleep behavior disorder (RBD) and cognitive test scores using age-and education-adjusted GLM. Results: Women had lower CSF α-syn levels (F 1429 ± 164 vs M 1831 ± 60, p = 0.02) and CSF Aβ42 levels (F 712 ± 39 vs M 821 ± 18, p = 0.01) compared to men. There were no sex differences for (p) Tau concentrations (p > 0.05). Clinically, women were older, had a shorter duration of complaints (F 2 ± 1 vs M 4 ± 3, p < 0.001), more frequent hallucinations (58% vs 38%, p = 0.02), and scored lower on MMSE and a fluency task (MMSE, p = 0.02; animal fluency, p = 0.006). Men and women did not differ on fluctuations, RBD, parkinsonism, or other cognitive tests.

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“…Males have approximately four times the incidence rate of DLB compared to females [Savica et al, 2013], though visual hallucinations are reportedly more common in females [Chiu et al, 2018], particularly at older ages and in the context of more severe neuropsychiatric symptoms. Recent work suggests that DLB is more prevalent in females than males after age 75, which may reflect a survival bias [Mouton et al, 2018]. Sex differences have been less frequently studied in DLB than other LBDs.…”

Section: Dementia With Lewy Bodiesmentioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen¹,

Tubi²,

Bright³

et al. 2020

Preprint

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Sex differences are found in the incidence and expression of psychiatric and neurodegenerative conditions, and many studies suggest these differences are influenced by innate biological differences between males and females and risk factors that interact with these differences. However, few studies have used neuroimaging to examine brain signatures of disease separately by sex, and many studies of sex differences have been based on small samples and their findings have not been replicated in larger cohorts. Large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses (ENIGMA) consortium, the UK Biobank, Human Connectome Project, and others offer an unprecedented source of power to address important questions about the role of sex as a risk or protective factor for suboptimal brain health, as well as sex-specific neuroimaging phenotypes in brain-related illnesses. Here we review the existing neuroimaging literature on sex differences in the human brain in healthy adults and those with the most common and debilitating psychiatric and age-related neurodegenerative conditions. Finally, we discuss key gaps in this literature and opportunities of large-scale collaborative efforts to identify, characterize, and explain how biological sex influences the humanbrain in health and disease.

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Sex ratio in dementia with Lewy bodies balanced between Alzheimer’s disease and Parkinson’s disease dementia: a cross-sectional study

Cited by 52 publications

References 32 publications

Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants

Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants

Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

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