The relationship between objective and subjective executive function in Parkinson's disease.

INTRODUCTION: Difficulties in executive functioning (EF) are common in PD; however, the relationship between subjective and objective EF is unclear. Understanding this relationship could help guide clinical EF assessment. This study examined the relationship between subjective self-reported EF (SEF) and objective EF (OEF) and predictors of SEF-OEF discrepancies in PD. METHOD: One-hundred and sixteen non-demented PD participants completed measures of OEF (i.e. problem-solving, cognitive flexibility, inhibition, and working memory) and SEF (Frontal Systems Behavior Scale-Self Executive Dysfunction Subscale). Pearson bivariate correlations and linear regressions were performed to examine the relationship between SEF and OEF and the non-motor symptoms (e.g. mood, fatigue), demographic, and PD characteristic (e.g. MCI status) predictors of discrepancies between OEF and SEF (|OEF minus SEF scores|). Correlates of under-, over-, and accurate-reporting were also explored. RESULTS: Greater SEF complaints and worse OEF were significantly associated (ß =.200, p = .009) and 64% of participants accurately identified their level of OEF abilities. Fewer years of education and greater symptoms of depression, anxiety, and fatigue significantly correlated with greater discrepancies between OEF and SEF. Fatigue was the best predictor of EF discrepancy in the overall sample (ß = .281, p = .022). Exploratory analyses revealed apathy and fatigue associated with greater under-reporting, while anxiety associated with greater over-reporting. CONCLUSIONS: SEF and OEF are significantly related in PD. Approximately 64% of non-demented persons with PD accurately reported their EF skill level, while 28% under-reported and 8% over-reported. SEF-OEF discrepancies were predicted by fatigue in the overall sample. Preliminary evidence suggests reduced apathy and fatigue symptoms relate to more under-reporting, while anxiety relates to greater over-reporting. Given the prevalence of these non-motor symptoms in PD, it is important to carefully consider them when assessing EF in PD.

Associations of category fluency clustering performance with in vivo brain pathology in autosomal dominant Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer's disease (ADAD). METHODS: A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations. RESULTS: Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers. CONCLUSION: This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease.

INTRODUCTION: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. METHODS: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. RESULTS: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. DISCUSSION: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. HIGHLIGHTS: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers.