scholarly journals Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers

2019 ◽  
Vol 5 (1) ◽  
pp. 158-169
Author(s):  
Michelle M Mielke
Keyword(s):  
Sex Differences ◽  
Alzheimer Disease ◽  
Amyloid Β ◽  
Structure And Function ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Current State ◽  
Brain Structure And Function ◽  
And Function ◽  
The Impact

Abstract Background The development of cerebrospinal fluid and blood-based biomarkers for Alzheimer disease (AD) and related disorders is rapidly progressing. Such biomarkers may be used clinically to screen the population, to enhance diagnosis, or to help determine prognosis. Although the use of precision medicine methods has contributed to enhanced understanding of the AD pathophysiological changes and development of assays, one aspect not commonly considered is sex differences. Content There are several ways in which sex can affect the concentration or interpretation of biofluid biomarkers. For some markers, concentrations will vary by sex. For others, the concentrations might not vary by sex, but the impact or interpretation may vary by sex depending on the context of use (e.g., diagnostic vs prognostic). Finally, for others, there will be no sex differences in concentrations or their interpretation. This review will first provide a basis for sex differences, including differences in brain structure and function, and the means by which these differences could contribute to sex differences in biomarker concentrations. Next, the current state of sex differences in AD-related biofluid markers (i.e., amyloid-β, phosphorylated τ, total τ, neurofilament light chain, and neurogranin) will be reviewed. Lastly, factors that can lead to the misinterpretation of observed sex differences in biomarkers (either providing evidence for or against) will be considered. Summary This review is intended to provide an impetus to consider sex differences in the measurement and interpretation of AD-related biofluid-based biomarkers.

scholarly journals The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76815 ◽  
Author(s):  
Esther Walton ◽  
Daniel Geisler ◽  
Johanna Hass ◽  
Jingyu Liu ◽  
Jessica Turner ◽  
...  
Keyword(s):  
Brain Structure ◽  
Structure And Function ◽  
Risk Variants ◽  
Genome Wide ◽  
Brain Structure And Function ◽  
And Function ◽  
The Impact

Temporal Correlation of CSF and Neuroimaging in the Amyloid-Tau-Neurodegeneration Model of Alzheimer Disease

Neurology ◽  
2021 ◽  
Author(s):  
Anna H. Boerwinkle ◽  
Julie K. Wisch ◽  
Charles D. Chen ◽  
Brian A. Gordon ◽  
Omar Hameed Butt ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cortical Thickness ◽  
Light Chain ◽  
Amyloid Β ◽  
Time Interval ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Total Tau ◽  
Maximal Correlation

Objective:Temporal correlations between CSF and neuroimaging (PET and MRI) measures of amyloid, tau, and neurodegeneration were evaluated in relation to Alzheimer disease (AD) progression.Methods:Three hundred seventy-one cognitively unimpaired and impaired participants enrolled in longitudinal studies of AD had both CSF (amyloid-β42, phosphorylated tau181, total tau, and neurofilament light chain) and neuroimaging (PiB PET, flortaucipir PET, and structural MRI) measures. The pairwise time interval between CSF and neuroimaging measures was binned into two year periods. Spearman correlations identified the time bin when CSF and neuroimaging measures most strongly correlated. CSF and neuroimaging measures were then binarized as biomarker-positive or biomarker-negative using Gaussian mixture modelling. Cohen’s kappa coefficient identified the time bin when CSF measures best agreed with corresponding neuroimaging measures when determining amyloid, tau, and neurodegeneration biomarker positivity.Results:CSF amyloid-β42 and PiB PET showed maximal correlation when collected within six years of each other (R ≈ -0.5). CSF phosphorylated tau181 and flortaucipir PET showed maximal correlation when CSF was collected four to eight years prior to PET (R ≈ 0.4). CSF neurofilament light chain and cortical thickness showed low correlation, regardless of time interval (Ravg ≈ -0.3). Similarly, CSF total tau and cortical thickness had low correlation, regardless of time interval (Ravg < -0.2).Conclusions:CSF amyloid-β42 and PiB PET best agree when acquired in close temporal proximity, whereas CSF phosphorylated tau precedes flortaucipir PET by four to eight years. CSF and neuroimaging measures of neurodegeneration have low correspondence and are not interchangeable at any time interval.

scholarly journals Beyond sex differences: new approaches for thinking about variation in brain structure and function

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150451 ◽  
Author(s):  
Daphna Joel ◽  
Anne Fausto-Sterling
Keyword(s):  
Sex Differences ◽  
Brain Structure ◽  
Well Being ◽  
Structure And Function ◽  
Laboratory Animals ◽  
Sex And Gender ◽  
Sex Effects ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being.

What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review

2015 ◽  
Vol 45 (12) ◽  
pp. 2461-2480 ◽  
Author(s):  
R. Gurung ◽  
D. P. Prata
Keyword(s):  
Bipolar Disorder ◽  
Brain Structure ◽  
Association Studies ◽  
Structure And Function ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Brain Structure And Function ◽  
And Function ◽  
The Impact

The powerful genome-wide association studies (GWAS) revealed common mutations that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD), but the vast majority were not known to be functional or associated with these illnesses. To help fill this gap, their impact on human brain structure and function has been examined. We systematically discuss this output to facilitate its timely integration in the psychosis research field; and encourage reflection for future research. Irrespective of imaging modality, studies addressing the effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1, NCANandZNF804A) were included. Most GWAS risk variations were reported to affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3andZNF804A), volume (CACNA1CandZNF804A) and density (ZNF804A); grey-matter (CACNA1C, NRGN, TCF4andZNF804A) and ventricular (TCF4) volume; cortical folding (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3, CACNA1C, DGKH, NRGNandZNF804A) and functional connectivity during executive tasks (CACNA1CandZNF804A), facial affect recognition (CACNA1CandZNF804A) and theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist. Further efforts such as standardizing reporting and exploring complementary designs, are warranted to test the reproducibility of these early findings.

The impact of bilingualism on brain structure and function in Huntington's disease

2019 ◽  
Vol 60 ◽  
pp. 92-97 ◽  
Author(s):  
Saul Martínez-Horta ◽  
Andrea Moreu ◽  
Jesús Perez-Perez ◽  
Frederic Sampedro ◽  
Andrea Horta-Barba ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Structure ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
And Function ◽  
The Impact

Sex Differences in Cognition: The New Rise of Biologism

1993 ◽  
Vol 10 (1) ◽  
pp. 2-5
Author(s):  
Lesley J. Rogers
Keyword(s):  
Sex Differences ◽  
Brain Structure ◽  
Structure And Function ◽  
Representation Of Women ◽  
Brain Structure And Function ◽  
Environmental Stimulation ◽  
And Function ◽  
The Brain

AbstractCurrently there is an increase in the number of articles published in scientific journals and in the popular scientific media that claim a biological basis for sex differences in cognition and in certain structures in the brain. It can be argued that there is over-emphasis on the differences rather than similarities between the sexes, but it is even more important to question the assumed causation of the differences. This paper discusses recent evidence for an interactive role of early experience and hormonal condition in determining sex differences in brain structure and function. Although early studies using rats were thought to show that the male sex hormone, testosterone, acts on the brain in early life to direct its differentiation into either the male or female form, it is know known that this result comes about indirectly by changing the mother’s behaviour towards the pups. The hormone does not act on the brain directly but rather it alters the environment in which the young animals are rasied and this, in turn, influences the development of the brain. Indeed, the brain is in dynamic register with its environment both during development and in adulthood. Other examples also show that old ideas of rigid biological determination of brain structure and function need to be laid aside.The hypotheses for hormonal causation of sex differences humans rely heavily, if not exclusively, on the earlier interpretation of the experiments with rats, and there seems to be resistance to changing these notions based on the new discoveries. Apparently, there is strong pressure to cling on to biological determinist theories for sex differences in behaviour, and this has profound effects on social and educational policy. For example, biological determinism has been used to justify under representation of women in certain professions. Realisation of the dramatic effects that environmental stimulation and learning can have on the development of brain and behaviour leads us to an optimistic position for social change towards equality for women.

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