Neuropsychiatric symptoms, such as depression, anxiety, apathy, agitation, and hallucinations, are frequent in Alzheimer's disease (AD) and their prevalence tends to increase with external stressors.
...We offer the first investigation of the effects of confinement during the COVID-19 crisis on neuropsychiatric symptoms in patients with AD.
We contacted caregivers of 38 patients with AD who were confined to their homes for nearly two months and asked them to report whether patients experienced any change in neuropsychiatric symptoms during, compared to before, the confinement and rate its severity and impact on themselves using the Neuropsychiatric Inventory-Questionnaire.
Among the 38 patients, only 10 demonstrated neuropsychiatric changes during the confinement. Cognitive function of these 10 patients, assessed with the Mini-Mental State Examination, was worse than that of patients who did not demonstrate neuropsychiatric changes. Interestingly, among the 10 patients with neuropsychiatric changes, the duration of confinement significantly correlated with the severity of symptoms as well as with their caregivers' distress.
The confinement seems to impact neuropsychiatric symptomatology in AD patients with low baseline cognitive function.
The objective of this study was twofold. We assessed whether individuals with Alzheimer's disease (AD) demonstrate higher empathy toward people with the same disorder. We also assessed whether ...empathy may enhance the recognition of these peoples' faces.
Twenty-seven mild AD participants and 30 healthy older adults were invited to retain faces depicting either people diagnosed with AD or healthy people. Participants were also invited to rate their empathy toward all faces.
Although AD participants reported higher empathy for "AD-labeled" than for "healthy" faces, recognition was similar for both categories of faces. Healthy older adults also reported higher empathy for "AD-labeled" than for "healthy" faces. However, they demonstrated higher recognition for "healthy" than for "AD-labeled" faces.
Although our paper shows no effect of empathy on face recognition in AD, it provides a clinically relevant finding: individuals with mild AD can demonstrate significant empathy toward people with the same medical condition.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to ...test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints.
The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aβ42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period.
Overall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46,
< 0.0001) and were associated with amyloid-PET status (
< 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 95% CI = 0.69; 0.79). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 95% CI = 0.69; 0.77); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 95% CI = 0.69; 0.97) than in patients with CDR = 0.5 (c-index = 0.70 95% CI = 0.66; 0.74). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 95% CI = 0.86-0.91 and performance increased to 0.90 95% CI = 0.88; 0.92 when adding blood p181-tau + Aβ42/40. A "research" reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 95% CI = 0.89-0.93 increasing to 0.92 95% CI = 0.90; 0.93 when adding blood p181-tau + Aβ42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances.
In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.
Background
Dementia with Lewy bodies remains underdiagnosed in clinical practice mainly because of the low sensitivity of existing diagnostic criteria and a strong overlap with Alzheimer’s pathology ...that can mask the Lewy phenotype.
Objective
The objective of this study was therefore to develop and validate a new clinical scale designed to detect signs of Lewy body disease, called LeSCoD for Lewy body Screening scale in Cognitive Disorders.
Methods
128 patients who fulfilled the clinical criteria of dementia with Lewy bodies (DLB;
n
= 32), Alzheimer’s disease (AD;
n
= 77) or both (
n
= 19) was prospectively enrolled.
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F-DOPA PET imaging and/or CSF biomarkers were available in some patients. LeSCoD scale was systematically administered and the potential correlation with
18
F-DOPA PET imaging was evaluated in a subgroup of patients.
Results
LeSCoD scale showed robust internal and external validity. We determined a cut-off of 10 above which the sensitivity and specificity for Lewy body disease diagnosis were 86% and 95%, respectively. The LeSCoD scale correlated with striatal dopamine uptake in
18
F-DOPA PET.
Conclusion
LeSCoD scale is a simple and reliable tool for the evaluation of Lewy body disease in routine clinical practice, with a higher sensitivity and specificity than the existing criteria. It might be an alternative to the use of dopamine-specific imaging.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Platelet-derived growth factor receptor beta (PDGFRB) is one of the genes associated with primary familial brain calcification (PFBC), an inherited neurological disease (OMIM:173410). ...Genetic analysis of patients and families revealed at least 13 PDGFRB heterozygous missense variants, including two novel ones described in the present report. Limited experimental data published on five of these variants had suggested that they decrease the receptor activity. No functional information was available on the impact of variants located within the receptor extracellular domains. Here, we performed a comprehensive molecular analysis of PDGFRB variants linked to PFBC. Mutated receptors were transfected in various cell lines to monitor receptor expression, signaling, mitogenic activity and ligand binding. Four mutants caused a complete loss of tyrosine kinase activity in multiple assays. One of the novel variants, p.Pro154Ser, decreased the receptor expression and abolished binding of platelet-derived growth factor (PDGF-BB). Others showed a partial loss of function related to reduced expression or signaling. Combining clinical, genetic and molecular data, we consider nine variants as pathogenic or likely pathogenic, three as benign or likely benign and one as a variant of unknown significance. We discuss the possible relationship between the variant residual activity, incomplete penetrance, brain calcification and neurological symptoms. In conclusion, we identified distinct molecular mechanisms whereby PDGFRB variants may result in a receptor loss of function. This work will facilitate genetic counseling in PFBC.
The COVID-19 crisis has been increasing the burden of healthcare workers in acute care geriatric facilities. These workers have been dealing with drastic changes in the care they provide to their ...residents including cancelation of group activities and communal dining and even restrictions of activities outside rooms. Healthcare workers have also been devoting more time and energy to perform COVID-related medical duties. Geriatric facilities have been facing shortages in equipment and supplies, as well as staffing shortages. Finally, healthcare workers have been facing challenges regarding their personal safety and that of their families. Consequently, we hypothesized the presence of high levels of burnout among healthcare workers during the COVID-19 crisis.
To evaluate burnout in healthcare workers in French acute care geriatric facilities, we used an online survey based on the Oldenburg Burnout Inventory. Eighty-four healthcare workers answered the survey, during April of 2020.
Analysis demonstrated that they were experiencing medium levels of burnout, exhaustion, and disengagement.
This level of burnout reflected their fatigue, loss of energy, and/or feelings of being overextended and exhausted. Considering the expected cumulative impact of various stressors, the medium level of burnout observed has come as a surprise to us and might actually be considered as relatively good news. Nevertheless, no level of burnout is negligible and has wide ranging negative consequences.
Introduction: The clinical presentation of the behavioral variant of frontotemporal dementia (bvFTD) differs from that of Alzheimer disease (AD), with major impairments in behavioral functions in ...bvFTD and cognitive impairment in AD. Both behavioral disturbances in bvFTD and cognitive impairment in AD contribute to caregiver burden. Objective: To investigate the impact of home confinement during the COVID-19 crisis on the burden of caregivers of bvFTD or AD patients. Methods: During the COVID-19 lockdown in France, neurologists and neuropsychologists from the Memory Center of Nantes Hospital conducted teleconsultations for 38 AD patients and 38 bvFTD patients as well as for their caregivers. During these consultations, caregivers were invited to rate the change in their burden during home confinement. They were also invited to rate behavioral or emotional changes in the patients during, compared with before, the confinement. Results: Twenty-two bvFTD caregivers and 14 AD caregivers experienced an increase in burden. For bvFTD caregivers, this increased burden occurred regardless of behavioral changes, while AD caregivers experienced an increased burden related to changes in patients’ neuropsychiatric symptoms. Among the whole cohort, 2 factors were associated with increased caregiver burden: behavioral change and bvFTD. Conclusion: The results demonstrate that during home confinement in the COVID-19 crisis, neuropsychiatric symptoms were the core factor that impacted caregiver burden in different ways depending on the disease.
GRN mutations are frequent causes of familial frontotemporal degeneration. Although there is no clear consensual threshold, plasma progranulin levels represent an efficient biomarker for predicting ...GRN mutations when decreased. We evaluated plasma levels to determine whether it could also predict age at onset, clinical phenotype, or disease progression in 160 GRN carriers. Importantly, progranulin levels were influenced by gender, with lower levels in male than in female patients in our study. Although we found no correlation with age at onset or with clinical phenotype, we confirmed that decreased level predicts GRN mutations, even in presymptomatic carriers more than four decades before disease onset. We also provided first evidence for the stability of levels throughout longitudinal trajectory in carriers, over a 4-year time span. Finally, we confirmed that progranulin levels constitute a reliable, cost-effective marker, suitable as a screening tool in patients with familial frontotemporal degeneration, and more broadly in patients without family history or with atypical presentations who are less likely to be referred for molecular diagnosis.
•Plasma progranulin levels were analyzed in 293 GRN carriers and controls.•Progranulin levels were stable in carriers and controls over a 4-year time span.•Plasma progranulin did not correlate with age at onset and FTD phenotypes.•Different thresholds were suggested for male and female carriers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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