Parkinson disease (PD) is a progressive neurodegenerative disorder that is 1.5 times more common in males than in females. While motor progression tends to be more aggressive in males, little is known about sex difference in cognitive progression. We tested the hypothesis that there are sex differences in cognitive dysfunction in non-demented PD. We evaluated 84 participants (38 females) with PD and 59 controls (27 females) for demographic variables and cognitive function, including attention, working memory, executive function, and processing speed. Multivariate ANOVA revealed no significant differences between groups for demographic variables, including age, years of education, global cogntition, daytime sleepiness, predicted premorbid IQ, UPDRS score, PD phenotype, or disease duration. For cognitive variables, we found poorer performance in males versus females with PD for measures of executive function and processing speed, but no difference between male and female controls. Specifically, PD males showed greater deficits in Verbal Fluency (category fluency, category switching, and category switching accuracy), Color Word Interference (inhibition), and speed of processing (SDMT). There were no differences in measures of working memory or attention across sex and inconsistent findings for switching. Our data indicate that males with PD have significantly greater executive and processing speed impairments compared to females despite no differences in demographic variables or other measures of disease severity. Our findings are consistent with the steeper slope of disease progression reported in males with PD.

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention.

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Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.

Prenatal ethanol exposure can negatively affect development, causing physical and/or cognitive deficits in the offspring. Behavioral changes are typically characterized during childhood, but they can also persist into adulthood. The extent of Fetal Alcohol Spectrum Disorder (FASD) abnormalities depends upon the amount and manner of ethanol intake, leading to a large variety of animal models. In order to mimic the genetically diverse human condition, we examined an outbred strain of mice exposed to chronic gestational ethanol and characterized subsequent behavioral alterations during adulthood. To detect deficits in cognitive ability and/or motor function, we ran the mice through tests designed to detect either memory/learning ability or motor strength/skill. We tested cognitive responses using the Barnes Maze and the Open Field Aversion Test, and motor skills using Kondziela's Inverted Screen Test and the rotarod. As adults, the FASD mice showed no significant differences on grip strength, open field, or the Barnes maze; however, we found that outbred mice who had experienced moderate prenatal ethanol exposure were slower to learn the rotarod as adults, though they did not differ in overall performance. Our data suggest a specific FASD vulnerability in motor learning ability, and also open the door to further investigation on the effect of ethanol on brain areas involved in motor learning, including the striatum.

Objectives: This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete. Methods: One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups. Results: Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding. Conclusions: Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.

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