Amyloid beta and postoperative delirium: partners in crime or strangers in the dark?

Postoperative delirium is a particularly debilitating complication of surgery and perioperative care. Although the aetiology of postoperative delirium is not entirely understood, recent evidence suggests that Alzheimer's disease and related dementias pathology plays an important role in the development of postoperative delirium. A recent study evaluating postoperative changes in plasma beta amyloid (Aß) levels found increased Aß across the postoperative period, but the association with postoperative delirium incidence and severity was variable. These findings support the idea that Alzheimer's disease and related dementias pathology in combination with blood-brain barrier dysfunction and neuroinflammation may impart risk for postoperative delirium.

Sex differences in Parkinson disease-associated episodic memory and processing speed deficits.

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.

Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias.

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) and its metabolites (acid-labile (e.g., iron-sulfur clusters) and bound (e.g., per-, poly-) sulfides) have been shown to modulate both vascular and neuronal homeostasis. We recently reported that elevated plasma sulfides were associated with cognitive dysfunction and measures of microvascular disease in ADRD. Here we extend our previous work to show associations between elevated sulfides and magnetic resonance-based metrics of brain atrophy and white matter integrity. Elevated bound sulfides were associated with decreased grey matter volume, while increased acid labile sulfides were associated with decreased white matter integrity and greater ventricular volume. These findings are consistent with alterations in sulfide metabolism in ADRD which may represent maladaptive responses to oxidative stress.

Evaluating racial disparities in healthcare system utilization and caregiver burden among older adults with dementia.

OBJECTIVE: To evaluate racial differences in healthcare utilization and caregiver burden in a culturally diverse population of older adults with dementia. METHOD: One hundred and thirty-three dyads (person with dementia, PWD and caregiver, CG), with at least one emergency department (ED) visit or hospitalization 12 months prior, were enrolled. Independent sample t-tests and chi-squared analyses were performed to compare racial groups on healthcare utilization and CG burden. Mann-Whitney U test was used for item-level analyses, principal component analysis was used to examine relationships among outcomes, and regressions were used to identify the relationship between race and potential covariates. RESULTS: PWD sample mean age was 79 years, predominantly female, and with high school education. Racial distribution was 65% White and 35% Black. CG sample mean age was 64 years, predominantly female, with more than 12 years of education. No differences were found for age or dementia severity across racial groups. Black PWD experienced more ED and ambulance utilization when compared to White counterparts. Non-emergency hospitalization rates were higher for White PWD. No significant differences were found by race for CG burden total score; however, item-level analysis suggested more anger, reduced social life, uncertainty, and inadequacy in White CGs. Regressions demonstrated a positive relationship between Black race and adult-child CGs with increased ED visits, while dyad educational attainment was associated with hospitalizations independent of race. CONCLUSIONS: Healthcare utilization disparities extend to older adults with dementia diagnoses. Our findings suggest that culturally tailored interventions may be appropriate. Future research is encouraged to explore the effect of other covariates.

Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias.

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 (H2 S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2 S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2 S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2 S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2 S 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 H2 S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention.

Acute Ethanol Exposure during Synaptogenesis Rapidly Alters Medium Spiny Neuron Morphology and Synaptic Protein Expression in the Dorsal Striatum.

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.

Sex specific cognitive differences in Parkinson disease.

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.