Sex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not ...been assessed in pathologically confirmed participants.
Core DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer's Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden.
In the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria.
Sex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.
To investigate the risk of impairment in cognitive instrumental activities of daily living (IADL) for people with Parkinson's (PwP) identifying as sexual and/or gender minorities (SGM).
Data were ...obtained from Fox Insight, an online, longitudinal study with self/informant-report questionnaires from PwP and people without Parkinson's. Groups consisted of PwP without cognitive IADL impairment at baseline, identifying as (1) SGM with female sex assigned at birth (SGM-F,
= 75); (2) cisgender, heterosexual with female sex assigned at birth (CH-F,
= 2046); (3) SGM with male sex assigned at birth (SGM-M,
= 84); (4) cisgender, heterosexual with male sex assigned at birth (CH-M,
= 2056). Impairment in cognitive IADL was based on Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15). Group differences for PDAQ-15 and impairment likelihood during follow-up were assessed with unadjusted models and adjusting for variables that differed between the groups.
SGM-F were the youngest at Parkinson's diagnosis; SGM-M had the lowest PDAQ-15 at baseline (
≤ .014 for all). Scores declined more for males than females in unadjusted and adjusted models (
< .001 for both). In unadjusted models, SGM-M had a higher impairment risk than PwP identifying as cisgender and heterosexual (
≤ .018). In adjusted models, females had a lower impairment risk than males (
< .001). Age, education, and discrimination level were significant moderators (
< .001 for all).
SGM-M can be at a higher risk for impairment in cognitive IADL, associated with social determinants. Female sex assigned at birth may be associated with a lower level of impairment risk, although this advantage can disappear with social determinants.
Random Forests variable importance measures are often used to rank variables by their relevance to a classification problem and subsequently reduce the number of model inputs in high-dimensional data ...sets, thus increasing computational efficiency. However, as a result of the way that training data and predictor variables are randomly selected for use in constructing each tree and splitting each node, it is also well known that if too few trees are generated, variable importance rankings tend to differ between model runs. In this letter, we characterize the effect of the number of trees (ntree) and class separability on the stability of variable importance rankings and develop a systematic approach to define the number of model runs and/or trees required to achieve stability in variable importance measures. Results demonstrate that both a large ntree for a single model run, or averaged values across multiple model runs with fewer trees, are sufficient for achieving stable mean importance values. While the latter is far more computationally efficient, both the methods tend to lead to the same ranking of variables. Moreover, the optimal number of model runs differs depending on the separability of classes. Recommendations are made to users regarding how to determine the number of model runs and/or trees that are required to achieve stable variable importance rankings.
The dengue and Zika viruses are primarily transmitted by Aedes aegypti mosquitoes, which are most active during day light hours and feed both in and outside of the household. Personal protection ...technologies such as insecticide-treated clothing could provide individual protection. Here we assessed the efficacy of permethrin-treated clothing on personal protection in the laboratory.
The effect of washing on treated clothing, skin coverage and protection against resistant and susceptible Ae. aegypti was assessed using modified WHO arm-in-cage assays. Coverage was further assessed using free-flight room tests to investigate the protective efficacy of unwashed factory-dipped permethrin-treated clothing. Clothing was worn as full coverage (long sleeves and trousers) and partial coverage (short sleeves and shorts). Residual permethrin on the skin and its effect on mosquitoes was measured using modified WHO cone assays and quantified using high-pressure liquid chromatography (HPLC) analysis.
In the arm-in-cage assays, unwashed clothing reduced landing by 58.9% (95% CI 49.2-66.9) and biting by 28.5% (95% CI 22.5-34.0), but reduced to 18.5% (95% CI 14.7-22.3) and 11.1% (95% CI 8.5-13.8) respectively after 10 washes. Landing and biting for resistant and susceptible strains was not significantly different (p<0.05). In free-flight room tests, full coverage treated clothing reduced landing by 24.3% (95% CI 17.4-31.7) and biting by 91% (95% CI 82.2-95.9) with partial coverage reducing landing and biting by 26.4% (95% CI 20.3-31.2) and 49.3% (95% CI 42.1-59.1) respectively with coverage type having no significant difference on landing (p<0.05). Residual permethrin was present on the skin in low amounts (0.0041mg/cm2), but still produced a KD of >80% one hour after wearing treated clothing.
Whilst partially covering the body with permethrin-treated clothing provided some protection against biting, wearing treated clothing with long sleeves and trousers provided the highest form of protection. Washing treated clothing dramatically reduced protection provided. Permethrin-treated clothing could provide protection to individuals from Ae. aegypti that show permethrin resistance. Additionally, it could continue to provide protection even after the clothing has been worn. Field trials are urgently needed to determine whether clothing can protect against dengue and Zika.
•Parkinson’s disease with freezing of gait is associated with sleep and mood problems.•Non-motor Parkinson’s disease symptoms can predict freezing of gait development.•Processing speed, learning ...decline, and increased sleepiness predict future freezing.
The etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.
We aimed to determine the predictive value of non-motor features in freezing of gait development.
Data were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.
Patients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.
Our findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.
Studies have shown that women on the Alzheimer's disease (AD) continuum have more pathological tau in the brain and cerebrospinal fluid (CSF), than men. Some studies have found that higher levels of ...tau biomarkers are more strongly associated with clinical AD, cognitive decline and neurodegeneration in women than in men. Despite major developments in the use of plasma tau phosphorylated at threonine 181 (p-tau181) as an AD biomarker, it is unknown whether these sex differences apply to plasma p-tau181. In 1060 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (47% women, 73.8 ± 7.6 years old), we examined sex differences in plasma p-tau181 levels and their association with other biomarkers, cognitive decline and incident AD. Linear regressions tested for an effect of sex on plasma p-tau181 levels and for plasma p-tau181 × sex interactions on CSF p-tau181, as well as entorhinal cortex tau, cortical amyloid-β (Aβ) deposition, and brain glucose metabolism, quantified using PET imaging. Linear mixed effects models tested for a sex × baseline plasma p-tau181 interaction on change in cognition over time. Finally, Cox models tested for a sex × plasma p-tau181 interaction on the risk of AD dementia in participants who were free of dementia at baseline. Despite similar plasma p-tau181 levels between sexes, women had lower brain glucose metabolism, greater brain Aβ and entorhinal cortex tau deposition, higher CSF p-tau181 and faster cognitive decline in relation to higher baseline plasma p-tau181 levels compared with men. Among Aβ positive, dementia-free participants, women had higher rates of incident AD dementia associated with increasing baseline plasma p-tau181 levels, relative to men. Our results suggest that sex may impact the clinical interpretation of plasma p-tau181 concentrations. If replicated, these findings could have important implications for the use of plasma p-tau181 as an accessible AD biomarker and screening tool for preventive and therapeutic clinical trials.
To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic ...traumatic encephalopathy (CTE).
A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES
April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298).
Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features.
New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
Better characterization of the relationship between episodic memory and hippocampal volumes is crucial in early detection of neurodegenerative disease. We examined these relationships in a memory ...clinic population.
Participants (n = 226) underwent structural magnetic resonance imaging and tests of verbal (Hopkins Verbal Learning Test-Revised, HVLT-R) and non-verbal (Brief Visuospatial Memory Test-Revised, BVMT-R) memory. Correlational analyses were performed, and analyses on clinical subgroups (i.e., amnestic Mild Cognitive Impairment, non-amnestic Mild Cognitive Impairment, probable Alzheimer's disease, intact memory) were conducted.
Positive associations were identified between bilateral hippocampal volumes and both memory measures, and BVMT-R learning slope was more strongly positively associated with hippocampal volumes than HVLT-R learning slope. Amnestic Mild Cognitive Impairment (aMCI) participants showed specific positive associations between BVMT-R performance and hippocampal volumes bilaterally. Additionally, analyses of the aMCI group showed trend-level evidence of material-specific lateralization, such that retention of verbal information was positively associated with left hippocampal volume, whereas learning curve and retention of non-verbal information was positively associated with right hippocampal volume.
Findings support the link between episodic memory and hippocampal volumes in a memory clinic population. Non-verbal memory measures also may have higher diagnostic value, particularly in individuals at elevated risk for Alzheimer's disease.
Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional ...combatants.
224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed.
Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment.
Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.