bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐report of seriousness of forgetting predicts objective memory ability in older adults with subjective cognitive decline
Authors: Mah Linda , Murari Geetanjali , Vandermorris Susan , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan 
Published: December 2021

AbstractBackgroundPrevious work in subjective cognitive decline (SCD) suggests that subjective memory and other cognitive concerns are more likely to be associated with mood or anxiety, rather than objective memory performance, but the overall literature is inconsistent. In the current study, subjective memory profiles were characterized to examine differences amongst SCD, mild cognitive impairment (MCI), and cognitively unimpaired (CU) older adults and to determine their association with mood, anxiety, and objective memory in SCD.MethodsParticipants were 33 MCI [17F, age 72.3(SD6.7)], 71 SCD [49F, age 71.1(SD6.3)] and 42 CU [27F, age 70.6(SD6.8)] free of lifetime history of psychiatric illness and neurological conditions. They completed the Memory Functioning Questionnaire (MFQ), a measure of subjective memory according to Frequency of Forgetting (FF), Seriousness of Forgetting (SF), Retrospective Functioning (RF), and Mnemonics Usage (MU), with higher scores indicating better subjective memory; as well as Geriatric Depression Scale (GDS), State Trait Anxiety Inventory (STAI), Health Anxiety Inventory (HAI) and NEO Five‐Factor Inventory (NEO‐FFI). Multivariate ANOVA was used to examine group differences in MFQ, followed by post hoc comparisons using Dunnett’s test. Relationships between MFQ and mood and anxiety measures within groups were assessed using Pearson’s correlation. Linear regression modelling with subjective memory and mood/anxiety as predictors of performance on the California Verbal Learning Test (CVLT) was conducted in SCD.ResultsGroups differed in total MFQ, FF, and SF, with total MFQ reduced in MCI and SCD. However, FF and SF were decreased in MCI and SCD respectively. SF was inversely associated with NEO‐FF neuroticism in CN, and with HAI in MCI participants. Within SCD, both SF and FF were inversely associated with NEO‐FFI neuroticism, HAI, STAI‐trait, and GDS. Further, SF, but neither FF nor any mood or anxiety measure, predicted CVLT immediate and long delayed recall in SCD.ConclusionsConsistent with previous research, perception of poorer subjective memory was correlated with greater anxiety and depression symptoms in SCD. Despite these associations, subjective memory, as characterized by perceived seriousness of memory slips, was predictive of objective memory in SCD. These findings highlight the need to better understand the phenomenology of subjective memory in SCD.
Evolution of core features in Lewy body disease pathologic subtypes
Authors: Choudhury Parichita , Graff‐Radford Jonathan , Aakre Jeremiah A , Wurtz Lincoln , Knopman David S. , Graff‐Radford Neill R. , Savica Rodolfo , Kantarci Kejal , Fields Julie A. , Pedraza Otto , Reichard Ross R. , Petersen Ronald C. , Dickson Dennis W , Boeve Bradley F. , Ferman Tanis J 
Published: December 2021

AbstractBackgroundNeocortical tau can be present in over half of patients with Lewy body disease at autopsy, and may influence the timing of when a diagnosis of Dementia with Lewy bodies (DLB) can be made. We examined whether the core features, onset age and latency of probable DLB diagnosis differ by pathological subgroups.MethodAll patients (n=176) met clinical criteria for probable DLB, underwent autopsy and were classified as transitional or diffuse Lewy body disease (TLBD, DLBD). The TLBD and DLBD groups were further subdivided based on the absence of neocortical tangles represented by a low (L) Braak NFT stage of 0‐III or by the presence of neocortical tangles represented by a high (H) Braak NFT stage of IV‐VI. Onset age and latency from cognitive symptom onset to probable DLB were compared for TLBD‐L (n=30), DLBD‐L (n=47), DLBD‐H (n=78) and TLBD‐H (n=21).ResultThe TLBD‐H group met criteria for DLB at an older age (median 76 years) compared to TLBD‐L, DLBD‐L or DLBD‐H groups (median age 70 years, p<0.001). The latency to probable DLB from cognitive onset was shortest for TLBD‐L and DLBD‐L (median < 1 year), which was shorter than DLBD‐H (median 2 years; p=0.016), each of which were shorter than TLBD‐H (median 7.3 years; p<0.001). RBD was more common in men (79% men vs. 40% women, p<0.001) and in patients without neocortical tangles (86% vs. 57%, p<0.001). Patients with RBD met criteria for probable DLB at a younger age than those without a history of RBD (median 69 years vs. 76 years, p<0.001). Men had a shorter latency to probable DLB than women (median 1.0 year vs. 2.8 years, p<0.01), but this was related to RBD status that was more common in men.ConclusionPresence of RBD in both sexes led to a younger onset age and shorter latency to diagnosis of probable DLB. Patients with more widespread tau relative to α‐synuclein pathology (TLBD‐H) were older when probable DLB was diagnosed compared to those with so‐called pure Lewy body disease (TLBD‐L, DLBD‐L) or those with diffuse α‐synuclein and tau pathology (DLBD‐H).
The role of worry in subjective cognitive decline
Authors: Mah Linda , Vandermorris Susan , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan 
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD) is defined as self‐report of memory or other cognitive decline with normal test performance, but there is lack of consensus regarding operational criteria for SCD. One fundamental question is whether perception of cognitive decline is sufficient to establish SCD, or whether accompanying concern or worry about the cognitive change is another core feature. The goal of the current study was to characterize clinical and neuroimaging characteristics of older adults with subjective memory decline with worry (SCD+W) and without worry (SCD‐W).MethodsParticipants were diagnosed based on psychiatric/medical assessment, neuropsychological (NP) test performance, and responses to 1)“Do you feel like your memory is becoming worse?”; 2)“If so, are you worried?”. The sample included 71 SCD+W [49F, age 71.1(SD6.3)] and 20 SCD‐W [15F, age 72.5(SD6.9)] based on normal NP scores and responses of yes/yes and yes/no respectively, 33 MCI [17F, age 72.3(SD7.6)] defined as subjective cognitive complaints, impaired NP performance and functional independence, and 16 CU [8F, age 69.2(SD7.2)]] based on normal NP and absence of subjective memory decline/worry. Participants completed subjective memory, depression, state‐trait anxiety, and health anxiety scales. Resting state functional magnetic resonance imaging (rs‐fMRI) was acquired in a subset [24 SCD+W, 12 SCD‐W, 12 CU] to assess default mode network (DMN) connectivity. Group effects were evaluated using multivariate ANOVA followed by Sidak‐adjusted post‐hoc comparisons.ResultsRelative to CU, SCD+W and MCI participants endorsed poorer subjective memory (P’s<.001), greater trait anxiety (P’s<.05) and greater health anxiety (P’s<.02). SCD‐W and CU did not differ on any measure. On rs‐fMRI, a significant group effect was found for DMN‐parahippocampal connectivity [F(2, 45)=5.35, P=.008], which was attributable to lower DMN‐parahippocampal connectivity in SCD+W compared to CU (P=.006). This finding remained significant with trait anxiety or health anxiety included as covariates.ConclusionsSimilar to MCI, SCD+W participants showed poorer subjective memory ability and greater trait and health anxiety, while SCD‐W did not differ from CU. Disrupted neural connectivity was found in SCD+W only, suggesting worry may define a subgroup of SCD patients with distinct neurobiology than those without worry. Longitudinal studies are needed to determine the prognostic significance of worry.
Telephone cognitive screening with older aboriginal Australians: A preliminary study
Authors: Veinovic Madeleine , Hill Thi Yen , Lavrencic Louise , Lasschuit Danielle , Broe Gerald A , Delbaere Kim , Draper Brian , Garvey Gail , Radford Kylie 
Published: December 2021

AbstractBackgroundCognitive assessment via telehealth is being increasingly employed, particularly in the context of the COVID‐19 pandemic. Widespread access to video call software has improved the availability and quality of telehealth services however inequity of access to such technologies remains for some communities, especially when restricted to home‐based telehealth options. As such, telephone adaptations of existing cognitive screening tests need to be validated across diverse populations.MethodThe present study sought to evaluate an existing 26‐point telephone adaptation of the Mini Mental State Examination (TMMSE) in a sample of older Aboriginal Australians. Additionally, we aimed to evaluate a novel urban telephone adaptation of the Aboriginal‐specific Kimberly Indigenous Cognitive Examination short form (TKICA‐screen). A sub‐sample (n=20) of participants (age range: 55‐69 years; MMSE range: 23‐30), who had completed in‐person cognitive assessment (MMSE and KICA‐screen) within the past 6 months as part of the Koori Growing Old Well Study, completed telephone‐based cognitive testing using the TMMSE and TKICA‐screen.ResultThere was a moderate positive correlation between MMSE versions (r=.583; p=.011) with poorer performance on the TMMSE for Season (p=.016) and Phrase (p=.016) items. A weak correlation was observed between the KICA‐screen and TKICA‐screen (r=.196; p=.407) with participant’s performing significantly worse on the TKICA‐screen for Season (p=.016) and Picture Recall (p=0.001). Demographic factors, including age, sex and education were not associated with telephone screening performance. Participants with hearing problems performed worse than those without on the TKICA‐screen (p=.042), but there was no significant difference found on TMMSE (p=.609).ConclusionThis small pragmatic study had a number of limitations, but preliminary results indicate that the TMMSE may be a suitable alternative to the in‐person test in this population. However, the TKICA‐screen requires further revision and evaluation. Clinically, service‐to‐service video telehealth has enabled the continuation of geriatric medicine and dementia outreach clinics to rural Aboriginal community controlled health services throughout pandemic‐related public health restrictions. There is potential for telehealth services to enhance remote access to culturally safe dementia assessment, diagnosis and specialist care services for older Aboriginal Australians, but further research is required, particularly validation of cognitive assessment approaches.
Novel measures to assess the association of IPA agitation criteria domains with cognition, caregiver burden and quality of life in dementia
Authors: Guan Lily T , Sekhon Ramnik , Kaur Sharanjit , Chen Hung‐Yu , K.V. Vineetha Warriyar , Burhan Amer M. , Colman Sarah , Derkach Peter , Elmi Sarah , Hussain Maria , Krisman Linda , Nair Vasavan , Rej Soham , Rostas Aviva , Streiner David , Van Bussel Lisa , Rajji Tarek K. , Kumar Sanjeev , Ismail Zahinoor ,   the StaN Study Group
Published: December 2021

AbstractBackgroundSyndromic agitation as per International Psychogeriatric Association (IPA) criteria consists of three domains: verbal aggression (VA), physical aggression (PA), and excessive motor activity (EMA). The relationships between these domains and cognition, caregiver burden, and patient quality of life are not well established. We examined these associations utilizing data from a multisite clinical trial using novel measures for these domains.MethodBaseline participant data (n=128) from Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study were utilized. Recently described IPA domain‐specific measures were implemented: domain prevalence was assessed with the NPI‐C‐IPA (derived from the Neuropsychiatric Inventory Clinician rating scale) and the CMAI‐IPA (derived from the Cohen Mansfield Agitation Inventory). Kendall’s Tau‐B was utilized for correlations between agitation domains from both scales and the Montreal Cognitive Assessment (MoCA), Severe Cognitive Impairment Rating Scale (SCIRS), Zarit Burden Inventory (ZBI), and Alzheimer’s Disease Related Quality of Life (ADRQL).ResultUsing the NPI‐C‐IPA, 58.3% of participants had EMA, 58.3% VA, and 72.2% PA. With the CMAI‐IPA, 70.1% had EMA, 66.9% VA, and 45.2% PA. PA in both derived rating scales was correlated with poorer performance on the SCIRS (NPI‐C‐IPA: τb= ‐.21, p = .01, CMAI‐IPA: τb= ‐.29, p<.001). NPI‐C‐IPA EMA was correlated with poorer MoCA performance (τb= ‐.31, p=.01). Agitation in all three domains on the NPI‐C‐IPA was correlated with greater caregiver burden (EMA: τb=.16, p =.02, VA: τb=.14, p=.04, PA: τb=.15, p =.02), whereas only EMA was correlated with caregiver burden on the CMAI‐IPA (τb=.13, p=.04). Across both derived scales, the PA and VA domains were significantly correlated with poorer patient quality of life (NPI‐C‐IPA VA: τb
= ‐.13, p=.04, NPI‐C‐IPA PA: τb= ‐.16, p=.01, CMAI‐IPA VA: τb= ‐.14, p =.03, CMAI‐IPA PA: τb
= ‐.26, p <.001).ConclusionThe NPI‐C‐IPA and CMAI‐IPA both capture the IPA agitation domains, although differently. Domains measured with the NPI‐C‐IPA were more likely to correlate with the cognitive, caregiver burden, and quality of life outcomes compared to the CMAI‐IPA. Further research is required to determine the clinical significance of the differences in associations, and other salient domain‐specific features of the IPA agitation syndrome.
Left ventricular hypertrophy and incident cognitive impairment in elderly hypertensive patients: Hypertension in the Very Elderly Trial
Authors: Xu Ying , Bouliotis George , Beckett Nigel S , Warwick Jane , Antikainen Riitta L , Anderson Craig S , Bulpitt Christopher J , Peters Ruth 
Published: December 2021

AbstractBackgroundWe assessed whether left ventricular hypertrophy (LVH), as an indicator of hypertensive target organ damage, was associated with subsequent cognitive decline.MethodWe used data collected in the Hypertension in the Very Elderly Trial (HYVET). HYVET was a double‐blind placebo‐controlled trial of antihypertensives in hypertensive older adults (≥80 years). Trial treatment was not associated with cognitive decline, allowing us to analyze the trial data as a cohort. The baseline characteristics of the analytical sample and those who were excluded due to missing electrocardiography (ECG) values or cognitive outcomes were compared. LVH was assessed using a 12‐lead ECG based on Cornell product criterion. The Mini‐Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to ≤24 or an annual fall of ≥three points was defined as cognitive decline. Proportional hazard regression, including a competing risk Fine‐Gray model to account for competing outcomes (stroke, heart failure, myocardial infarction, other fatal cardiovascular disease), was used to examine the relationship between baseline LVH and cognitive outcomes. Sensitivity analyses were run in those with baseline MMSE ≥24, considered unlikely to have pre‐existing cognitive decline. To evaluate attrition bias, we ran inverse probability weighting (IPW) models.ResultThere were 1944 in the analytical sample, 164 with LVH. Mean follow‐up was 3.9 or 4.2 years accounting or not accounting for competing outcomes. The analytical sample differed from those excluded, e.g. they had higher diastolic blood pressures and were more likely to be female (Table 1). LVH was associated with increased risk of 1) cognitive decline (Table 2), hazard ratio (HR)1.44 (95%confidence interval (CI)1.12:1.84), 2) combined cardiovascular events and cognitive decline, HR1.51 (95% CI 1.2:1.91), and 3) cognitive decline using the Fine‐Gray model, HR1.41 (95%CI 1.08:1.84). Sensitivity and IPW analyses yielded similar results.ConclusionCP criterion defined LVH was associated with an increased risk of cognitive decline in older adults with hypertension. The potential for selection bias and healthy individual bias (trial participants) should be noted. Further work should explore the potential for LVH as an indicator of target organ damage beyond the heart.
Discovery of a‐synuclein degraders as potential therapeutics for Parkinson's disease
Authors: Lin Yih‐Shyan , Tempest Paul , Jang Ming‐Kuei 
Published: December 2021

AbstractBackgroundParkinson's disease (PD) is a progressive neurodegenerative disorder with a hallmark feature of intraneuronal inclusions termed Lewy bodies (LBs), which is defined by aggregated, b‐sheet rich a‐synuclein (a‐syn) fibrils. The misfolded a‐syn aggregates are widely accepted to play a key role in PD pathogenesis and regarded as potential therapeutic target.MethodHerein, we describe the development of a family of degrader compounds, which recruit E3 ubiquitin ligase to specifically eliminate a‐syn aggregates.ResultOur degraders have been demonstrated to selectively recognize pathological a‐syn aggregates derived form a patient with dementia with Lewy bodies (DLB) over tau aggregates from an Alzheimer patient. More importantly, these degraders trigger proteasome‐dependent eliminations of a‐syn aggregates in ReNcell VM neuronal model. The half‐maximal concentrations (DC50) are within nanomolar range. Furthermore, the degraders are capable of crossing blood‐brain barrier (BBB) when systemically administrations a dose at 25 mg/kg to C57BL/6 mice via intravenous (IV) injection. The brain AUCs have achieved > 1000 (hr*ng/mL).ConclusionThe results suggest that development of a‐syn degraders represents a potential therapeutic strategy for treatment of PD.
Progression of metabolic brain patterns in common dementias
Authors: Perovnik Matej , Krejan Karmen , Tomše Petra , Rus Tomaž , Ležaić Luka , Kramberger Milica G , Pirtošek Zvezdan , Trost Maja 
Published: December 2021

AbstractBackgroundNeurodegenerative dementias are chronic progressive syndromes. The neurodegenerative process can be well observed with the metabolic brain imaging, which reveals typical patterns of regional hypometabolism. The specific metabolic brain patterns have been previously identified for the common dementia syndromes using 18F‐FDG PET scans and SSM/PCA network analysis and they represent a metabolic biomarker of neurodegenerative process. Aims: The aim of this retrospective study was to analyse changes in the expression of the three characteristic metabolic patterns: Alzheimer’s disease related pattern (ADRP), frontotemporal dementia related pattern (FTDRP) and dementia with Lewy bodies related pattern (DLBRP), from the 18F‐FDG PET scans in a cohort of patients with cognitive decline, who were scanned with 18F‐FDG PET twice.MethodWe analysed clinical data and 18F‐FDG PET brain scans from 25 patients with cognitive decline due to AD (n=5), FTD (n=6), DLB (n=7) and non‐AD cognitively stable mild cognitive impairment (MCI, n=7) who underwent two 18F‐FDG PET imaging, within 2.9 years. We performed TPR network analysis to measure the expression of ADRP, FTDRP and DLBRP in all 18F‐FDG PET scans. Then we calculated absolute difference in pattern expression between the two scans and fitted a series of linear models to examine slopes of progression.ResultsIn AD group we have observed a larger increase of ADRP‐Z scores (β=1.21, p<0.001) in comparison to FTDRP‐z (β=0.98) or DLBRP‐Z (β=0.07). In FTD group we have observed a larger increase of FTDRP‐Z scores (β=0.85, p<0.001) in comparison to ADRP‐Z (β=0.43) or DLBRP‐Z (β=‐0.36). In DLB group we have observed the highest coefficient for ADRP‐Z (β=0.84), followed by DLBRP‐Z (β=0.45) and FTDRP‐Z (β=0.14). On the other hand, DLBRP expression progressed in time in DLB group, but not in AD or FTD group. In MCI group FTDRP‐Z expression scores remained stable, while ADRP‐Z and DLBRP‐Z scores decreased in time.ConclusionsCharacteristic and dementia specific metabolic brain patterns have proved to be a reliable imaging biomarker of the disease progression in common dementia syndromes. As the diseases progresses, the expression of corresponding patterns increases.
Impairment of EEG functional connectivity in dementia during recognition of emotional facial expression
Authors: Uzunlar Hakan , Kıyı İlayda , Bayraktaroglu Zubeyir , Hanoğlu Lutfu , Yener Gorsev , Güntekin Bahar 
Published: December 2021

AbstractBackgroundThe performance of facial expression recognition is affected both in neurocognitive disorders and in healthy elderly. Emotional content processing is expected to be adversely affected in dementia and as well in Parkinson's disease patients. The present study aims to compare the impaired facial expression recognition between different types of dementia patients, functional connectivity changes in patients with mild cognitive impairment, and patients with dementia were investigated by event‐related EEG‐coherence.Method25 Healthy elderly controls (HC), 25 Mild Cognitive Impairment patients (MCI), 25 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease with Mild Cognitive Impairment (PDMCI), and 16 patients with Parkinson's disease Dementia (PDD) were included in the study. EEG was recorded while angry, happy, and neutral facial expressions were presented. The artifacts were rejected by using Independent‐Component‐Analysis and Current‐Source‐Density. Magnitude‐squared coherence values of theta (4‐7Hz, 50‐400ms) responses were calculated. Inter‐hemispheric and intra‐hemispheric (frontal and central centered) pairs of F3, F4, C3, C4, T7, T8, Tp7, Tp8, P3, P4, O1, O2 channels were used. Two separate inter and intra hemispheric repeated‐measures‐ANOVA models were used for group comparisons.ResultThere were no group differences for intra‐hemispheric comparisons, but GroupXLocation comparison (p=.040) was significant, HE and MCI groups had higher coherence values in central‐ temporal, central‐ temporoparietal, and central‐ occipital connections compared to PDMCI, PDD, and AD patient groups (Figure 1). FaceXGroup (p=.009) interaction was significant for inter‐hemispheric coherence values, HC and MCI groups had higher interhemispheric coherence values than the PDMCI, PDD, and AD, especially during recognition of "angry" facial expression.ConclusionThe connectivity between the central and posterior regions increased with emotional face content; this increase seems to be preserved in MCI. On the other hand, it wasn't maintained in patients with more severe neurocognitive impairment; PDMCI, PDD, and AD groups had reduced central‐posterior connectivity and interhemispheric connectivity during the facial expression recognition paradigm. The decrease in inter and intra‐connectivity in the posterior regions is consistent with behavioral scores and may indicate neural losses as a phenomenon.