Sex and gender differences in cognitive and brain reserve: Implications for Alzheimer’s disease in women

Subramaniapillai, Sivaniya; Almey, Anne; Rajah, M. Natasha; Einstein, Gillian

doi:10.1016/j.yfrne.2020.100879

Cited by 109 publications

(95 citation statements)

References 60 publications

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“…As a pivotal result, we focused on the difference in cognitive reserve proxies between sexes. In our cohort, premorbid intelligence (measured as TIB) and years of education were lower in women compared to men, as commonly found in the literature [18]. In particular, we found a significant gap in premorbid intelligence between women and men with the same educational level.…”

Section: Discussionsupporting

confidence: 85%

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

et al. 2021

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Background Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. Methods We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. Results The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. Conclusions Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.

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Section: Discussionsupporting

confidence: 85%

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

et al. 2021

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“…Studies often report contradictory sex differences in cognitive abilities, and many are not replicated (Camarata & Woodcock, 2006;Fairweather, 1976;Gur & Gur, 2017;Irwing & Lynn, 2005;Kimura, 2004;Lynn & Irwing, 2004;Satterthwaite et al, 2015;Weis, Hodgetts, & Hausmann, 2019). In recent years, sex differences in cognitive manifestations of various neurological, neurodevelopmental, and neuropsychiatric illnesses have become increasingly evident (Han et al, 2012;Irvine, Laws, Gale, & Kondel, 2012;Laws, Irvine, & Gale, 2016;Subramaniapillai, Almey, Rajah, & Einstein, 2020). Insight into sex-independent and sex-specific brain-behaviour relationships in healthy young adults can enable better understanding of the neurobiological underpinnings of cognitive deficits within and across sexes, paving the way for the development and implementation of personalised treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Shared functional connections within and between cortical networks predict cognitive abilities in adult males and females

Dhamala

Jamison

Jaywant

et al. 2021

Preprint

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A thorough understanding of sex-independent and sex-specific neurobiological features that underlie cognitive abilities in healthy individuals is essential for the study of neurological illnesses in which males and females differentially experience and exhibit cognitive impairment. Here, we evaluate sex-independent and sex-specific relationships between functional connectivity and individual cognitive abilities in 392 healthy young adults (196 males) from the Human Connectome Project. First, we establish that sex-independent models comparably predict crystallised abilities in males and females, but more accurately predict fluid abilities in males. Second, we demonstrate sex-specific models comparably predict crystallised abilities within and between sexes, and generally fail to predict fluid abilities in either sex. Third, we reveal that largely overlapping connections between visual, dorsal attention, ventral attention, and default mode networks are associated with better performance on crystallised and fluid cognitive tests in males and females, while connections within visual, somatomotor, and default mode networks are associated with poorer performance. Together, our findings suggest that shared neurobiological features of the functional connectome underlie crystallised and fluid abilities across the sexes.

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“…We aimed to develop a practical and reproducible model for a quick and accurate patient diagnosis in an easy-to-handle way for an outpatient memory clinic setting. As age, sex and APOE4 status are the most well-known risk factors for AD 39,40 and are already part of an established diagnostic work -up in many memory clinic settings, we contemplated an extended risk model that included these risk factors in addition to plasma GFAP and NfL levels (age + sex + APOE4 + GFAP + NfL panel). To assess the best performance of each single biomarker, we furthermore analysed the impact of adding GFAP (age + sex + APOE4 + GFAP panel) or NfL alone (age + sex + APOE4 + NfL panel).…”

Section: Discussionmentioning

confidence: 99%

Promising Diagnostic Accuracy of Plasma GFAP and NfL Within The AD Continuum

Parvizi¹,

König²,

Wurm³

et al. 2021

Preprint

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Background: Blood-based biomarkers may add a great benefit in detecting the earliest neuropathological changes in patients with Alzheimer’s disease (AD). We examined the utility of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in plasma and cerebrospinal fluid (CSF) regarding clinical diagnosis and amyloid positivity in an outpatient memory clinic - based cohort. Methods: In this retrospective analysis, we included a total of 185 patients, 141 patients along clinical the AD continuum, i.e. subjective cognitive decline (SCD, n=18), mild cognitive impairment (MCI, n=63), AD (n=60) and 44 age-matched healthy controls (HC). CSF and plasma concentrations of NfL and GFAP were measured with single molecule array (SIMOAâ) technology using the Neurology 2-Plex B kit from Quanterix. Amyloid-PET was performed in 75 patients and graded as amyloid positive and negative by visual rating. To assess the discriminatory potential of different biomarkers, age- and sex-adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared using DeLong’s test for correlated AUC curves.Results: We constructed a panel combining plasma NfL and GFAP with known AD risk factors (age+sex+APOE4+GFAP+NfL panel). Using this panel, AUC was 91.6% for HC vs. AD, 81.7% for HC vs. MCI, 85% for SCD vs. AD, 81.3% for SCD vs. MCI, 77.7% for HC vs. SCD and 72.3% for MCI vs. AD. In terms of predicting amyloid PET status, we computed an AUC of 88.4%. Conclusion: The combination of plasma GFAP and NfL with well-established risk factors could contribute crucially to the identification of patients at risk, and thereby facilitate inclusion of patients in clinical trials for disease modifying therapies.

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Sex and gender differences in cognitive and brain reserve: Implications for Alzheimer’s disease in women

Cited by 109 publications

References 60 publications

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Shared functional connections within and between cortical networks predict cognitive abilities in adult males and females

Promising Diagnostic Accuracy of Plasma GFAP and NfL Within The AD Continuum

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