Search

Background and objectivesSynaptic dysfunction and degeneration is a predominant feature of brain aging and synaptic preservation buffers against Alzheimer's disease (AD) protein-related brain atrophy. We tested whether cerebrospinal fluid (CSF) synaptic protein concentrations similarly moderate the effects of axonal injury, indexed via CSF neurofilament light [NfL], on brain atrophy in clinically normal adults.MethodsClinically normal older adults enrolled in the observational Hillblom Aging Network study at the UCSF Memory and Aging Center completed baseline lumbar puncture and longitudinal brain MRI (Mean scan [follow-up]=2.6 [3.7 years]). CSF was assayed for synaptic proteins (synaptotagmin-1, synaptosomal-associated protein 2 [SNAP-25], neurogranin, growth associated protein 43 [GAP-43]), axonal injury (NfL), and core AD biomarkers (ptau181/Aβ42 ratio; reflecting AD proteinopathy). Ten bilateral temporo-parietal gray matter ROIs shown to be sensitive to clinical AD were summed to generate a composite temporo-parietal ROI. Linear mixed-effects models tested statistical moderation of baseline synaptic proteins on baseline NfL-related temporo-parietal trajectories, controlling for ptau181/Aβ42 ratios.ResultsForty-six clinically normal older adults (Mean age=70; 43% female) were included. Synaptic proteins exhibited small to medium correlations with NfL (r range: .10 to .36). Higher baseline NfL, but not ptau181/Aβ42 ratios, predicted steeper temporo-parietal atrophy (NfL x time: β=-0.08, p

Background: Synaptic dysfunction is closely associated with cognitive function in Alzheimer's disease (AD), and is present already in an early stage of the disease. Objective: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum. Methods: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A–) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4–2.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia. Results: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, β-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] –0.27[0.12] to –0.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] –0.10[0.04] to –0.15[0.05]) and SCD/MCI-A+ (St.B[SE] –0.07[0.03] to –0.12[0.03]), but not in SCD/MCI-A- (pinteraction < 0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] –1.75[0.58]), but not in the other groups (pinteraction < 0.05). Conclusions: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages. [ABSTRACT FROM AUTHOR]

Synaptic dysfunction and degeneration is likely the key pathophysiology for the progression of cognitive decline in various dementia disorders. Synaptic status can be monitored by measuring synaptic proteins in CSF. In this study, both known and new synaptic proteins were investigated and compared as potential biomarkers of synaptic dysfunction, particularly in the context of Alzheimer's disease (AD). Seventeen synaptic proteins were quantified in CSF using two different targeted mass spectrometry assays in the prospective Swedish BioFINDER-2 study. The study included 958 individuals, characterized as having mild cognitive impairment (MCI, n = 205), AD dementia (n = 149) and a spectrum of other neurodegenerative diseases (n = 171), in addition to cognitively unimpaired individuals (CU, n = 443). Synaptic protein levels were compared between diagnostic groups and their associations with cognitive decline and key neuroimaging measures (amyloid-β-PET, tau-PET and cortical thickness) were assessed. Among the 17 synaptic proteins examined, 14 were specifically elevated in the AD continuum. SNAP-25, 14-3-3 zeta/delta, β-synuclein, and neurogranin exhibited the highest discriminatory accuracy in differentiating AD dementia from controls (areas under the curve = 0.81–0.93). SNAP-25 and 14-3-3 zeta/delta also had the strongest associations with tau-PET, amyloid-β-PET and cortical thickness at baseline and were associated with longitudinal changes in these imaging biomarkers [β(standard error, SE) = −0.056(0.0006) to 0.058(0.005), P < 0.0001]. SNAP-25 was the strongest predictor of progression to AD dementia in non-demented individuals (hazard ratio = 2.11). In contrast, neuronal pentraxins were decreased in all neurodegenerative diseases (except for Parkinson's disease), and NPTX2 showed the strongest associations with subsequent cognitive decline [longitudinal Mini-Mental State Examination: β(SE) = 0.57(0.1), P ≤ 0.0001; and mPACC: β(SE) = 0.095(0.024), P ≤ 0.001] across the AD continuum. Interestingly, utilizing a ratio of the proteins that displayed higher levels in AD, such as SNAP-25 or 14-3-3 zeta/delta, over NPTX2 improved the biomarkers' associations with cognitive decline and brain atrophy. We found 14-3-3 zeta/delta and SNAP-25 to be especially promising as synaptic biomarkers of pathophysiological changes in AD. Neuronal pentraxins were identified as general indicators of neurodegeneration and associated with cognitive decline across various neurodegenerative dementias. Cognitive decline and brain atrophy were best predicted by ratios of SNAP-25/NPTX2 and 14-3-3 zeta/delta/NPTX2. [ABSTRACT FROM AUTHOR]

'What would an ideal social justice advocate look like, and how do our graduates compare?' is asked by training programs in the helping/health professions (e.g. counselling and psychology, nursing, and education) that have social justice advocacy (SJA) as a core competency. We demonstrate a method for answering this question empirically -- cognitive diagnostic modelling (CDM). We used the four dimensions of the Social Issues Advocacy Scale (SIAS; Nilsson, Marszalek, Linnemeyer, Bahner, & Hanson Misialek, 2011) as attributes of SJA, and fit SIAS responses to a CDM of 16 attribute mastery profiles. One-quarter of the sample had a profile suggesting SJA attitudes without action; one-fifth, a profile suggesting monitoring SJA in politics without participation; and one-eighth, a profile suggesting individuals rarely engage in action without SJA attitudes. We also found significant relationships between mastery profiles and degree pursued, degree field, and political affiliation. These results demonstrated the utility of CDM for training program assessment of SJA.

BACKGROUND: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPSvenous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings. METHODS: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p‐tau181 and p‐tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single‐molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers. RESULTS: All DPSvenous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPSvenous GFAP, NfL, p‐tau181, and p‐tau217 differed between CSF Aβ‐positive and ‐negative individuals and were associated with worsening cognition. DISCUSSION: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood‐based biomarkers to remote settings with simplified sampling conditions, storage, and logistics. Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPSvenous).DPSvenous biomarkers correlated with standard procedures and cognitive status.DPSvenous biomarkers had a good diagnostic accuracy discriminating amyloid status.Our findings show the potential interchangeability of DPSvenous and plasma sampling.DPSvenous may facilitate remote and temperature‐independent sampling for AD biomarker measurement.Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD. [ABSTRACT FROM AUTHOR]

This study investigated 65 school counselors' perception of classroom placement of twins and multiples. The results show that most of the participants had twins and multiples in their schools, but that they were neither aware of their school district nor building's policy regarding placement. Most participants supported early separation, already at preschool or kindergarten, and believed that separation would have a positive impact on the children's development. Yet, over 70% reported having no training on issues associated with twins and multiples in the school system. Implications for research and practice are addressed.