bluuebunny/crossref_metadata_2025 huggingface dataset:
The SYNERGIC RCTs from Can Thumbs Up: Canadian experience in migrating lifestyle interventions to an @Home‐based program to enhance cognition
Authors: Montero‐Odasso Manuel , Jarrett Pamela , Handrigan Grant , Chamard‐Witkowski Ludivine , Bouchard Danielle R , Tranchant Carole C , Yetman Linda , Belleville Sylvie , Chertkow Howard , Feldman Howard , Nygaard Haakon B , Almeida Quincy J , Bherer Louis , Liu‐Ambrose Teresa , Middleton Laura E , Speechley Mark R , Kamkar Nellie , McGibbon Chris A
Published: December 2021

Background

The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition), a large multi‐site randomized controlled trial (RCT), showed promising interim results that individuals with Mild Cognitive Impairment (MCI) who received aerobic exercise combined with progressive resistance training and cognitive training improved their global cognition. When the COVID‐19 pandemic put SYNERGIC on hold, we migrated our interventions and assessments remotely. This experience informed the design of the SYNERGIC@Home trial.

Method

The SYNERGIC trial was a multi‐site, double‐blinded, five‐arm, randomized controlled trial that assessed the potential synergistic effect of combining bi‐modal exercises (aerobic + progressive resistance training), cognitive training, and, vitamin D supplementation in older adults with MCI. Interventions were delivered for 20 weeks. Results present data in 10 participants who migrated to conducting interventions and assessments at home.

Result

Ten participants with MCI (mean age 73±6.4, ♀70%) from the SYNERGIC trial migrated to a virtual modality at month 2 of their intervention. Their adherence for the 2‐month in‐person exercise and cognitive training was 90.2%, while for the 4‐month home‐based intervention, it was 95.9%. Participants reported being able to use the digital platform (WebEx© and Zoom Healthcare©) assigned on the first session. Similarly, 95% of the assessments tests were completed, including cognitive (ADAS‐Cog 13), medical, and mobility assessments conducted remotely. One participant was only able to complete half of the assessments due to digital connection issues. Following remote administration of the SYNERGIC trial in this subset of participants, we set up logistics and obtained ethical approval for the SYNERGIC@Home trial, a pilot RCT fully delivered remotely in 64 older adults at risk of dementia.

Conclusion

Delivering progressive physical exercise and cognitive training at home was feasible in older adults at risk of dementia. Insights gained from this migration informed our SYNERGIC@Home pilot, which is based on the SYNERGIC trial, but will be delivered fully remotely. SYNERGIC@Home will recruit participants with MCI, Subjective Cognitive Impairment, and Normal Cognition and two or more risk factors for dementia. Remote interventions and assessment are becoming particularly important during the COVID‐19 pandemic in which research participation for older adults may only be possible through virtual platforms.
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

Background

Previous 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.

Methods

Participants 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.

Results

Groups 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.

Conclusions

Consistent 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

Background

Neocortical 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.

Method

All 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).

Result

The 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.

Conclusion

Presence 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

Background

Subjective 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).

Methods

Participants 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.

Results

Relative 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.

Conclusions

Similar 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

Background

Cognitive 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.

Method

The 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.

Result

There 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).

Conclusion

This 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

Background

Syndromic 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.

Method

Baseline 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).

Result

Using 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).

Conclusion

The 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

Background

We assessed whether left ventricular hypertrophy (LVH), as an indicator of hypertensive target organ damage, was associated with subsequent cognitive decline.

Method

We 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.

Result

There 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.

Conclusion

CP 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

Background

Parkinson'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.

Method

Herein, we describe the development of a family of degrader compounds, which recruit E3 ubiquitin ligase to specifically eliminate a‐syn aggregates.

Result

Our 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).

Conclusion

The 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

Background

Neurodegenerative 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.

Method

We 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.

Results

In 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.

Conclusions

Characteristic 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

Background

The 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.

Method

25 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.

Result

There 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.

Conclusion

The 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.
Associations of plasma neurofilament light protein levels with cognitive functions and brain structure parameters
Authors: Coors Annabell , Boenniger Meta M. , Santos Marina , Koch Alexandra , Zeng Weiyi , Ettinger Ulrich , Aziz N. Ahmad , Breteler Monique M.B.
Published: December 2021

Background

Neurofilament light (NfL) protein level is considered a non‐specific marker of neurodegeneration. NfL levels have been associated with established, non‐blood based neurodegenerative markers, including cognitive performance and reduced brain volume. However, most studies were small (N<300), and compared levels in patients (MCI, Alzheimer’s disease) with those in healthy controls. We investigated to what extent NfL levels are associated with cognitive performance and MRI measures of brain volume and microstructure, in a large non‐demented population‐based sample.

Method

The analyses were based on 4,578 participants (30‐95 years) of the Rhineland Study, a community‐based cohort study in Bonn, Germany. Plasma NfL levels were measured on the SIMOA platform. We assessed cognitive performance with tests for memory, processing speed, executive function and crystallized intelligence and an eye movement (EM) test battery. 3,206 persons underwent structural and diffusion weighted MR imaging. Imaging outcomes included volumetric measures (total brain, grey matter, white matter, hippocampus); diffusion tensor measures (fractional anisotropy; mean, radial, and axial diffusivity); and neurite orientation dispersion and density imaging (NODDI) measures. We used multivariable regression models to assess the relation between NfL levels and cognitive performance and MRI measures with adjustment for possible confounders.

Result

Across all participants, we found only negligibly small associations between NfL levels and cognitive performance, brain volumetric and diffusion tensor measures. However, age‐stratified analyses revealed that in age 40‐49 and from age 60 onwards higher NfL levels were associated with lower orientation dispersion index (ODI). In the 70‐ to 79‐year‐olds, higher NfL levels were additionally associated with higher prosaccade accuracy, higher mean, axial and radial diffusivity, higher extracellular and lower intracellular volume fraction and a lower neurite density index. In the 80+‐year‐olds, NfL levels were negatively associated with hippocampal and white matter volume and positively associated with fractional anisotropy and radial diffusivity.

Conclusion

Higher NfL levels were associated with smaller hippocampal volume and diffusion tensor and NODDI measures in older subjects. In younger persons (up to age 70 years), NfL levels were only associated with ODI. This suggests that NfL level is a sensitive marker of subtle changes in brain microstructure, especially in old age.
Like psychosis, like dementia: Nigella sativa oil enhanced olfactory and amygdalic phenotypes in socially isolated BALB/c mice model of schizophrenia
Authors: Folarin Royhaan , Bakare Falilat , Onamusi Barnabas
Published: December 2021

Background

Social isolation rearing (SIR) is a developmental schizophrenia model with characteristic behavioral symptoms like anxiety and olfactory deficits influenced by the amygdala and olfactory bulbs respectively. Psychiatric disorders and dementias are often comorbid, with neuropsychiatric disturbances constituting inherent component of Alzheimer’s. As long‐term side effects mar available antipsychotics, novel natural psycho‐dementia drugs are urgently needed. This study thus investigated Nigella sativa (NS) for its impacts on olfactory bulb and amygdalic phenotypes in socially isolated BALB/c mice.

Method

Fifty (50) male BALB/c mice weaned after 21 days of birth were grouped equally into five. CTRL and NS were reared socially and administered normal saline (1ml/kgbw) and Nigella sativa (1ml/kgbw) respectively. SIR‐NS, NS‐SIR and SIR were socially isolated and administered Nigella sativa (1ml/kgbw) post‐isolation, Nigella sativa pre‐isolation (through maternal exposure) and normal saline respectively. Respective administrations lasted 10 days while social isolation lasted 4 weeks. Amygdalic and olfactory bulb glutamate, GPX and dopamine levels as well as histo‐architecture were investigated in addition to body weights, relative brain weight, temperature, food and water consumption. Olfactory acuity was assayed with olfactory sensitivity and discrimination tests while anxiety levels were assayed with elevated plus maze. Statistical analysis was carried out using one‐way ANOVA at 95% CI.

Result

In addition to increased brain‐body weight ratios, Nigella sativa increased the glutamate and dopamine levels in the amygdala and olfactory bulb of socially isolated mice which were maternally exposed to Nigella sativa (NS‐SIR mice) compared to the untreated but isolated mice. GPX also increased in the amygdala of the NS‐SIR but not in the olfactory bulb. Maternal Nigella sativa exposure prevented olfactory insensitivity in the SIR mice but with no ameliorative effect on the open arm exploration time in the pre‐ or post‐treated mice compared with the untreated isolated mice. NS‐SIR animals exhibited better histoarchitecture than SIR mice, as evidenced by increased neuronal sizes, densities and neuro‐piliary staining.

Conclusion

Social isolation modelled olfactory and partial emotional deficits in BALB/c mice similar to schizophrenics. Maternal exposure to Nigella sativa showed significant prophylactic potentials against these deficits especially in olfaction. However, farther isolation distance between the animals is recommended for better results.
Event related delta and theta oscillations are reduced in severe obstructive sleep apnea as a possible electrophysiologial evidence of subtle cognitive changes
Authors: Yerlikaya Deniz , Bircan Behice , Öztura İbrahim , Yener Gorsev
Published: December 2021

Background

Obstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder that leads to widespread cognitive impairment when left untreated. OSAS is also reported as a risk factor for developing Alzheimer’s disease. Recent studies report a shared pathophysiology between OSAS and Alzheimer’s disease (Polsek et al., 2018; Baril et al., 2018). Working memory and attention related ERP P300 deficits were previously reported (for a review see, Raggi and Ferri, 2012). This study aims to investigate electrophysiological changes by using time‐frequency analysis to gain a better understanding on cognitive impairment in OSAS.

Method

56 severe OSAS patients and age, education and gender matched 33 healthy controls were participated to the study. Participants completed a classical auditory oddball task. A complex Morlet with Gabor normalization was applied and total power within four frequency bandwidths, delta (0.5‐3.5 Hz), theta (4‐7 Hz), alpha (8‐13 Hz), and beta (15‐30 Hz), was calculated using Event‐Related Spectral Perturbation (ERSP) analyses.

Result

OSAS patients had reduced delta and theta ERPS to target stimuli compared to healthy controls in repeated measures ANOVA yielding a significant main GROUP effect (respectively, [F(1,87)=9.181, p=0.003] and [F(1,87)=5.083, p=0.027]). No differences were found on alpha and beta power.

Conclusion

We found reduced delta and theta activity in severe OSAS patients. Delta EROs activity is associated with attention and decision making (Başar ve Stampfer, 1985; Stampfer ve Başar, 1985), whereas theta activity was associated with task induced activation of working memory (Yordanova et al. 2000). Reduced delta and theta EROs activity can be useful indices of subtle cognitive impairment in severe OSAS even before neuropsychological test. These results strengthen our understanding of the cognitive changes in OSAS by means of electrophysiological methodologies. This study was supported by Dokuz Eylul University Scientific Research Projects (Project Number: 2014.KB.SAG.058).
Abnormal event‐related EEG theta responses in patients with dementia with Lewy bodies and Parkinson's disease dementia
Authors: Yıldırım Ebru , Hanoğlu Lutfu , Güntekin Bahar
Published: December 2021

Background

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by intracellular Lewy bodies in the brain neurons and clinical symptoms including cognitive impairment and flucations, motor symptoms, and hallucinations with some differences, namely non‐motor symptoms appear earlier in DLB over PDD patients (McKeith et al., 2017). An unmet need in the actual diagnostic criteria is the availability of biomarkers probing working brain cognitive systems. A promising biomarker may be derived from the frequency analysis of electroencephalographic oscillatory responses (EROs) during cognitive demands, as a decrease of frontal‐central EROs at theta (4‐7 Hz) frequencies was reapatedly demonstrated in Alzheimer’s disease patients with mild cognitive impairment and dementia over cognitively unimpaired (CU) persons (Yener et al., 2007; Guntekin et al., 2008). In this line, the present study tested the hypothesis of abnormal event‐related EROs at theta frequencies in PDD and DLB patients.

Method

Electroencephalographic activity was recorded during a visual oddball paradigm (i.e., 30% of target stimuli requiring mental counting intermingled with 70% of stimuli to be ignored) in 15 PDD, 12 DLB, and 15 CU persons. EROs at theta power and phase‐locking were computed for the oddball target stimuli and compared among the groups (ANOVA, p < 0.05).

Result

As compared to the CU group, both PDD and DLB groups showed a strong topographically widespread reduction in ERO theta power (p < 0.005) (Figure 1). They also showed a strong reduction in ERO theta phase‐locking, especially in frontal‐central locations (p < 0.0001)( Figure 2).

Conclusion

The present study showed that ERO theta power and phase‐locking during a standard visual oddball paradigm probing visual focused attention and short‐term memory may be suitable biomarkers to investigate working cognitive brain systems in both PDD and LBD patients. References: 1) McKeith et al. (2017). 10.1212/WNL.0000000000004058 2) Yener et al. (2007). https://doi.org/10.1016/j.ijpsycho.2006.07.006. 3) Güntekin et al.(2008). 10.1016/j.brainres.2008.06.028
Improving research recruitment through participant input
Authors: Large Stephanie E , Munoz Haydee Izurieta , Davila Marcela , Hall James R , O'Bryant Sid , Johnson Leigh Ann
Published: December 2021

Background

Recruitment of older adults into aging research is a challenge. Several research studies and clinical trials have failed due to low participant enrollment. Older adults face many barriers to study participation (mistrust of research, lack of transportation, health status, etc.), so special efforts must be made to recruit them into research. We created a recruitment questionnaire with the goal of understanding how to better promote the study and to obtain participant suggestions of groups and locations where the study team could recruit new participants.

Method

The Health and Aging Brain Study: Health Disparities (HABS‐HD) is a community based research study of cognitive aging in diverse communities. We designed a voluntary exit questionnaire for current study participants regarding their recruitment preferences. The questionnaire included the following questions: 1) How did you find out about the study? 2) How can we promote the study to someone similar to you? 3)Which of the following advertising methods do you prefer? 4) Do you know any organization/group that would benefit from the study information? Questionnaire data was compiled and analyzed to assess recruitment preferences and suggestions.

Result

The total number of participants who responded to the questionnaire was 413. 26.9% of respondents stated that they would prefer TV as their main advertising method, followed by the internet (23%) and postal service (mail) (22.7%). Word of mouth was listed as the best way to promote the study (26.9%) followed by community engagement (16.2%) and church (8.2%). When asked for names of organizations, participants recommended tradition groups such as churches, senior centers, and retirement homes. Participants also recommended groups such as rotary clubs, veterans associations, libraries, and the community college senior education program.

Conclusion

Participants can assist in recruitment efforts through suggesting organizations that study personnel may not have reached out to. The input allows for assessment of recruitment and the suggestions can broaden the study’s reach.
A smartphone‐based self‐administered test of verbal episodic memory: Development and initial validation
Authors: Valentine Sophie , Hall John , Gagnon Julien , Binning Emily , Narayan Vaibhav A , Wittenberg Gayle , Jaeger Judith , Mosca Kenneth
Published: December 2021

Background

Remote, self‐administered assessment of cognitive impairment offers immense value to all those impacted by Alzheimer’s disease: patients, carers, healthcare professionals, researchers and pharmaceutical companies alike. The high cost, slow pace and inaccessibility of traditional methods for evaluating novel assessment tools maintains a chasm between innovation and real‐world impact. Focusing on user‐centered design development and technical feature optimisation, we present the next generation of a digitisation of the examiner‐administered Rey Auditory Verbal Learning Test (RAVLT) (Morrison et al., 2018; Mackin et al., 2017) as a smartphone‐based self‐administered test of verbal episodic memory.

Method

A smartphone‐based version of RAVLT was developed, integrating artificial intelligence (AI), psychometric assessment principles and user‐centric design. Key risks to user acceptability were identified with moderated and unmoderated testing of the user interface (UI) in 11 users (aged 50+). AI speech‐recognition solutions implemented to replace traditional human components of RAVLT were tested for accuracy, via comparison to a human listener, in a real‐world environment (N = 13).

Result

All testers were able to complete the assessment without additional assistance, indicating high UI acceptability. Qualitative outcomes highlighted potential patient anxiety, insights which were used to iterate the UI design. AI solutions, when implemented alongside data‐driven adjustment features, achieved speech‐recognition accuracy of over 92%.

Conclusion

We present extrapolatable principles for developers of remote assessment tools. Thorough inclusion of patients in the development process is essential to ensure that technical and clinical accuracy can be mirrored by optimal adherence and patient experience. Novel technical solutions required to adapt clinic‐based tests for remote use must be validated in ecologically appropriate environments. A fully remote validation study is underway to assess user acceptability and speech‐recognition accuracy at scale in people with subjective memory complaints (SMC). These methods and results hold promise for the continued development of effective at‐home digital tools for remote assessment and reduction of time‐to‐market for innovations in Alzheimer’s disease and beyond. References: Morrison et al., 2018, Alzheimer’s Dement (Amst), 10, 647‐656. doi.org/10.1016/j.dadm.2018.08.010 Mackin et al., 2017, Alzheimer's & Dementia, 13, 598‐599. doi.org/10.1016/j.jalz.2017.07.239.
Parental education and delirium risk after surgery in older adults: A lifecourse analysis
Authors: Arias Franchesca , Chen Fan , Shiff Haley , Marcantonio Edward R , Jones Richard N , Travison Thomas G , Schmitt Eva M , Fong Tamara G , Inouye Sharon K
Published: December 2021

Background

Delirium is common in older adults and is a risk factor for long‐term cognitive decline. Efforts to conceptualize risk factors for delirium have focused on the time period proximate to the episode, and the role of early‐life exposures on delirium risk is poorly understood. Social and historical factors interact with psychological and biological predispositions, particularly during critical and sensitive periods in childhood, to influence health across the lifespan. Understanding the association between early life exposures and acute conditions occurring after surgeries provides an innovative first step in applying cumulative lifecourse models to examine perioperative risks and outcomes.

Method

Patients in the Successful Aging after Elective Surgery study, a cohort of adults 70+ scheduled for major non‐cardiac surgery, were interviewed prior to surgery to assess reading abilities. Cognitive functioning, neighborhood‐level characteristics, and medical co‐morbidities. Delirium incidence and severity were measured daily after surgery using the Confusion Assessment Method (CAM) and CAM‐severity (CAM‐S), respectively. Parental education and participation in cognitive stimulating activities were also assessed.

Result

In our sample of 547 patients, higher paternal education was associated with significantly lower incidence of delirium (odds ratio OR = 0.93, 95% CI [0.87, 0.98]) and inversely associated with delirium severity (Spearman’s rho = ‐.13, p < .001). Higher maternal education was associated with lower delirium incidence, but this association did not reach statistical significance. A multivariate model revealed that the effect of paternal education on delirium incidence was independent of the patient’s education, the patient’s verbal intelligence assessed pre‐operatively, medical comorbidities, neighborhood disadvantage, and participation in cognitively stimulating activities throughout the lifespan. Paternal education and general cognitive functioning at baseline explained about 10% of the variance in incidence of delirium (R2=.10, X2(7) =39.35, p<.001).

Conclusion

Paternal education is associated with delirium severity and predicts delirium incidence independent of other delirium risk factors. A life course perspective examining early‐life exposures may yield unique insights into the risks and pathogenesis of delirium. More broadly, this study represents a novel exploration in the field of delirium, and our results contribute to the growing body of literature on the early‐life exposures associated with health in adulthood and will into older age.
Sex differences in connectivity in the default mode network in healthy aging adults
Authors: Ficek Bronte , Horien Corey , Lacadie Cheryl , Shen Xilin , Scheinost Dustin , Constable Todd , Fredericks Carolyn A
Published: December 2021

Background

Two‐thirds of individuals diagnosed with Alzheimer’s disease (AD) are women, but the reasons for women’s elevated risk are unknown, and sex differences in brain aging trajectories are poorly understood. Both symptomatic AD and aging are associated with decreased connectivity within the default mode network (DMN), which supports short‐term memory processing, while individuals with preclinical AD show increased connectivity in some DMN regions. We sought to identify sex‐based differences in DMN connectivity over the lifespan in a large cross‐sectional study of healthy adults.

Method

We examined functional MRI data from a cross‐sectional cohort of n=595 cognitively normal individuals (aged 36‐100 years; 249 females) drawn from the Human Connectome Project‐Aging (HCP‐A) dataset (Harms et al., 2018; Bookheimer et al., 2019). Preprocessing followed our previously described pipeline, with stringent motion thresholds applied. The four resting‐state scans for each individual were averaged and masked to a standard DMN parcellation (Yeo et al., 2011). We calculated within‐network connectivity of each DMN voxel using the intrinsic connectivity distribution (ICD) (Scheinost et al., 2012), a robust voxel‐based metric of functional connectivity, and used a general linear model to assess the main effect of sex on within‐network ICD with increasing age.

Result

Females showed relative hyperconnectivity in posterior DMN with age compared to males, but lower connectivity in anterior nodes (Fig 1). Specifically, z‐scores for female minus male contrasts for posterior clusters were 3.9 (posterior cingulate), 4.5 (R angular gyrus), and 4.7 (L), and for anterior clusters were ‐4.1 (R frontal pole) and ‐4.3 (L).

Conclusion

In a large sample of healthy aging adults, women showed increased connectivity in posterior, and decreased connectivity in anterior, nodes of the DMN compared with their aging male counterparts. Interestingly, individuals with preclinical AD show a similar pattern of posterior hyperconnectivity, often interpreted as the compensatory response of a network under stress. These findings provide early clues to a potential role for network‐level sex differences in explaining women’s increased vulnerability to AD as they age.