bluuebunny/crossref_metadata_2025 huggingface dataset:
The protective impact of telecare on persons with dementia and their caregivers during the COVID‐19 pandemic
Authors: Ho‐yin Lai Frank , Wai‐hung Yan Elaine , Ka‐ying Yu Kathy , Tsui Wing Sze , Yee Benjamin K
Published: February 2022

Background

Social distancing under the COVID‐19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable alternative to face‐to‐face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video‐conferencing platforms could bring additional benefits to care‐recipient with NCD and their spousal caregivers at home.

Method

Sixty older adults NCD‐and‐caregiver dyads were recruited through an activity centre. The impact of additional services delivered to both care‐recipient and caregiver through video conference (n=30) was compared with telehealth targeted at caregivers by telephone only (n=30), over 4 weeks in a pretest‐posttest design. Interviews and questionnaires were conducted at baseline and study’s end.

Result

Supplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone‐only group (ηp2=0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL‐AD, ηp2=0.23). Varying degrees of improvements in physical and mental health (Short‐Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self‐efficacy (Revised Caregiving Self‐Efficacy Scale) were observed among caregivers in the video‐conferencing group, which were absent in the telephone‐only group (ηp2=0.23–0.51).

Conclusion

Telehealth by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehealth beyond the context of pandemic‐related social distancing should be considered.
The experiences of daughters caring for a parent with Alzheimer's disease in the home: A phenomenological study
Authors: DiLeone Christine
Published: February 2022

Background

An estimated 5.8 million Americans of all ages are living with Alzheimer’s Disease (AD) dementia as of 2019, which includes an estimated 5.6 million people age 65 and older. Of the 5.8 million people who have AD dementia, 81% are age 75 or older. Alzheimer’s disease is the 6th leading cause of death in the United States. By 2050, the number of people age 65 and older with AD dementia may grow to a projected 13.8 million, barring the development of medical breakthroughs to prevent, slow, or cure AD.

Method

The study used purposeful and snowball sampling. 12 daughters participated. Data were collected through in‐depth semi structured interviews. Data were analyzed using a Colaizzi’s (1978) descriptive phenomenological approach.

Result

Caregiving years ranged from 1‐10 years with a mean of 5 years. The average duration of caregiving reported by participants was 5 years. Six themes were uncovered: (a) Where Are You When I Need You? (b) Safety First (c) I Don’t Know What to Say or How to Say It (d) They Are Beautiful People, but They Aren’t Trained (e) Letting Go of Who They Were and (f) It Affects Every Area of My Life.

Conclusion

The study findings have implications for nursing education, research, and practice, and indicate a need for better support for daughters caring for their parent with AD in the home. They are struggling as they manage their parents’ care.
Larger hippocampal and brainstem volumes in high volume lumbar puncture responders as a predictor of shunt response in normal pressure hydrocephalus
Authors: Lotan Eyal , Damadian Brianna E. , Rusinek Henry , ades‐Aron Benjamin , Golomb James , George Ajax
Published: February 2022

Background

Normal pressure hydrocephalus (NPH) is a treatable cause of dementia, urinary incontinence and gait abnormality which is important to diagnose early as the longer the delay in treatment, the worse the outcome after shunting. Gait improvement following high volume lumbar puncture (HVLP) and continuous lumbar drain (cLD) is widely used to predict shunt responsiveness in patients with suspected NPH. Here, we investigate differences in MRI volumetric and traditional measures between HVLP/cLD responders and non‐responders to identify imaging features that may help predict shunt response.

Method

82 patients with suspected NPH were studied retrospectively. Gait testing was performed before and immediately/24‐hours/72‐hours after CSF removal. A positive response to HVLP/cLD was defined as improvement in gait following the procedure. The 36 responders (26 men; mean‐age 79.3±6.3) and 46 non‐responders (25 men; mean‐age 77.2±6.1) underwent pre‐procedure 3T brain MRI including 3D‐MPRAGE sequence. 66 subcortical regional volumes were segmented using FreeSurfer. After normalizing for total intracranial volume, two‐tailed student's t‐test and chi‐square test were used to characterize statistical group‐differences. Assessment of Evan’s‐index (EI), callosal‐angle (CA) and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were also made. Multivariable logistic regression models were tested using Akaike information criterion to determine which combination of metrics is most accurate in prediction of HVLP/cLD response.

Result

Responders and non‐responders demonstrated no differences in total ventricular and white/gray matter volumes and in EI and DESH. CA (in men) and third and fourth ventricular volumes were decreased; and hippocampal and brainstem volumes were increased in responders (p<0.05). Temporal horns volume correlated with degree of improvement in gait velocity in responders (p=0.0006). The regression model was 76.8% accurate for HVLP/cLD response with AUC of 0.81.

Conclusion

Imaging biomarkers, such as CA, third and fourth ventricular volumes and hippocampal and brainstem volumes, combined in a predictive model, may provide a useful noninvasive diagnostic supportive tool potentially helpful in (a) replacing the need for HVLP/cLD, and (b) predicting the success of shunt surgery. Larger hippocampi and brainstem in responders may reflect decreased rate of other comorbidities that contribute to hippocampal and brainstem atrophy, such as possible concomitant pathology of Alzheimer's disease, in responders as compared to non‐responders.
Rhythms of aging: Determining relationships between rhythm perception, learning, and performance
Authors: Colverson Aaron
Published: February 2022

Background

Many cognitive abilities change with age including how people experience, learn and perform music. Relatively little is known regarding effects of aging upon older adults’ abilities to perceive, learn, and perform rhythms. This is particularly the case for complex rhythms, defined here as multiple overlapping independent rhythms requiring simultaneous synchronization of neural structures across the brain to process. Knowledge of older adults’ ability to learn and perform complex rhythms may lead to interventions to improve cognitive functioning and quality of life in this population, potentially limiting incidence rates of decline into dementia‐related pathways.

Method

This research is divided into three contingent phases: 1) self‐report survey assessments of audience experiences listening to music; 2) in‐lab experiment; and 3) fMRI measurement of neurobehavioral correlates of rhythm processing in the aging brain. Phase 1 will determine self‐report experiences of pleasure and desire to move to music. Phase 2 will compare younger (ages 18‐35) and older (ages 55‐89) adults’ abilities to learn and perform progressively challenging rhythms. A comparative cohort of Latinx participants will be included to determine similarities and differences in rhythm learning and performance from a cross‐cultural perspective. Phase 3 will involve fMRI measurement to determine neurobehavioral correlates of rhythm processing in the aging brain.

Result

This work is prospective. Phase 1 data have been partially collected and analyzed, confirming the hypothesis that in conjunction, complex rhythms induce both pleasure from and desire to move to music. It is further hypothesized that simple rhythms will elicit less pleasure and desire to move in conjunction, as contrasted to complex rhythms. Phase 2 data collection is projected to begin in March 2021, and Phase 3, September 2021.

Conclusion

This research will address intergenerational, cross‐disciplinary, and cross‐cultural questions specific to meanings and uses of rhythm in humans’ lives. The intent is to broaden the ethnomusicological and anthropological discourse particular to the consideration of empiricism as reductionist, by incorporating empirical methods into ethnography‐based approaches addressing such topics. Furthermore, the intent of this research is to broaden awareness within empirically‐based research traditions as to the value of participant observation to enrich meaning‐making from quantitative results.
Diagnostic applications of tau PET
Authors: Rabinovici Gil D.
Published: February 2022

Background

Tau PET is useful for in vivo diagnosis of Alzheimer’s disease (AD) and may be useful in detecting non‐AD tauopathies. Diagnostic applications vary by tracer and AD disease stage.

Method

This presentation will review existing literature on the diagnostic utility of tau PET tracers across the AD continuum and in non‐AD tauopathies. Data from in vitro (autoradiography, brain homogenate binding) and in vivo studies will be reviewed, with an emphasis on large clinical studies and PET‐to‐autopsy correlations.

Result

In vitro and in vivo data suggest that [18]FTP, [18F]MK6240, [18F]GTP‐1, [18F]RO948 and [18F]JNJ‐067 are AD‐selective tau tracers, while [18F]PI2620 and [18F]PM‐PBB3 (also known as [18F]APN‐1607) may bind to non‐AD tauopathies. FTP‐PET quantification shows high accuracy in differentiating AD dementia from other disorders. In a multi‐site study conducted in Lund, Seoul and UCSF (N=719), FTP SUVR in in a temporal meta‐ROI showed 89.9% sensitivity and 90.6% specificity for AD dementia versus non‐AD disorders. Sensitivity in Aβ+ MCI was lower (61.5%) with similar specificity (90.6%). RO948 PET in the Swedish BioFinder‐2 study (N=613) showed similar diagnostic performance, though sensitivity in Aβ+ MCI was lower (37.5%). Data from Mayo Clinic (N=1,281) revealed that Aβ‐PET is more sensitive than FTP‐PET for detecting the AD continuum in cognitively unimpaired (29% of subjects Aβ+ vs. 5% tau+) and MCI (55% Aβ+ vs. 30% tau+), while sensitivity was similar in clinical AD dementia (97% Aβ+ vs. 89% tau+). PET‐to‐autopsy data from the Avid A16 trial, Mayo Clinic and UCSF cohorts show high sensitivity and specificity for FTP‐PET visual reads and quantification in detecting Braak Stages V‐VI, but low sensitivity for Braak Stages I‐IV. Antemortem FTP binding in these cohorts showed poor correlation with non‐AD tau pathology. In a multi‐site German study, [18F]PI‐2620 showed 77% sensitivity and specificity in discriminating Progressive Supranuclear Palsy (N=60) from disease (N=20) and healthy (N=10) controls.

Conclusion

Tau PET is most useful in differentiating AD from other causes of dementia but is less sensitive in detecting preclinical and prodromal AD, which are associated with earlier Braak stages. While most tau PET tracers are AD‐specific, [18F]PI2620 and [18F]PM‐PBB3 warrant further study in non‐AD tauopathies.
Towards clinical application of tau PET: Prognostics
Authors: Cho Hanna , Baek Minsuk , Kim Han‐Kyeol , Lee Jae Hoon , Chun Joong‐Hyun , Ryu Young Hoon , Lyoo Chul Hyoung
Published: February 2022

Background

Tau PET is now considered to be a disease stage biomarker for reflecting of Alzheimer’s disease (AD) severity. Recent longitudinal studies showed a progression of cortical tau burden and a predictability of baseline tau PET for further tau accumulation, cortical atrophy, and even clinical progression in the short term. In this study, we sought to investigate long‐term changes in tau burden and predictability of tau PET for long‐term disease progression.

Method

In a cohort with 273 participants who had completed visit 1 (V1) assessments including two PET scans (18F‐florbetaben and 18F‐flortaucipir), MR imaging studies and neuropsychological function tests, 77 Aβ+ participants [9 cognitively unimpaired (CU) and 38 mild cognitive impairment (MCI), and 30 AD dementia (DEM)] completed visit 2 (V2) assessments at two years, and subsequently 39 Aβ+ participants (6 CU, 24 MCI, and 9 DEM) completed visit 3 (V3) assessments at about four years (mean 4.6 years) after the V1 study. After correcting for partial volume effect, we measured regional standardized uptake value ratio (SUVR) values with cerebellar crus median as a reference and regional volumes, as well.

Result

During the short‐ (V1 to V2) and long‐term (V1 to V3) periods, tau burden significantly increased in the widespread cortex, particularly in the medial and lateral temporal cortices. In 33 cognitively impaired patients who completed both V2 and V3 scans, DEM patients exhibited higher global cortical tau accumulation rates (V1 to V2 = 0.066 and V2 to V3 = 0.058 SUVR/year) than MCI patients (V1 to V2 = 0.044 and V2 to V3 = 0.051 SUVR/year). Tau burden at V1 correlated strongly with the tau accumulation and volume reduction rates, particularly in the lateral temporal cortex and also correlated with the global cognitive decline rate, particularly in the prefrontal and parietal cortices. Likewise, in both short‐ and long‐term data, tau accumulation rate correlated with the volume reduction and global cognitive decline rates.

Conclusion

Tau accumulated progressively throughout a four year long‐term follow‐up period. Progression of tau pathology, cortical atrophy and cognitive decline can be predicted by baseline tau burden. Tau PET is a useful imaging biomarker in predicting long‐term disease progression.
Change in communication‐related participation in primary progressive apraxia of speech and aphasia
Authors: Utianski Rene L , Martin Peter R , Duffy Joseph R , Botha Hugo , Clark Heather M , Josephs Keith A
Published: February 2022

Background

Individuals with Primary Progressive Apraxia of Speech (PPAOS) have AOS as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. Past research has shown that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co‐occurring language deficits. Previous studies suggest measures of disease severity do not necessarily correlate with measures of participation restrictions. The aim of this study was to describe changes in communication limitations in these patients over a one‐year interval, measured by 1) the patient via the Communicative Participation Item Bank (CPIB) and 2) the speech‐language pathologist via ASHA's Functional Communication Measures (FCMs) and an adapted Motor Speech Disorder (MSD) severity rating and determine if there are significant changes in these and other objective speech and language measures (e.g. Western Aphasia Battery‐Revised Aphasia Quotient, Apraxia of Speech Rating Scale‐3).

Method

Seventeen patients (10 male) with progressive AOS were seen for a second visit approximately one year following the first visit. The measures collected at each visit were statistically compared. Correlations were calculated between the participation ratings and other clinical assessment measures at each visit and qualitatively compared.

Result

There were statistically significant differences in AOS and aphasia severity between visits. There were significant changes in clinical assessments, MSD severity rating, and all ASHA FCMs between visits, but not the CPIB. Comparison of correlations suggest the relationships among clinical and participation measures may change over time.

Conclusion

The findings of this study support the use of patient reported outcome measures, like the CPIB, as they may better reflect the patient experience and associated changes in day‐to‐day functioning when other measures may simply index the progression of the disease.
Cognitive health risks posed by social isolation and loneliness in older Korean Americans
Authors: Jang Yuri , Park Nan Sook , Chiriboga David A
Published: February 2022

Background

This study examines associations among social isolation, loneliness, and cognitive health risks in older Korean Americans, focusing on the mediating role of loneliness in the relationship between social isolation and objective and subjective measures of cognitive impairment.

Method

Data are from 2,061 participants in the Study of Older Korean Americans, a multi‐state survey of Korean immigrants age 60 and older (M
age = 73.2, SD = 7.93). Social isolation was indexed with the Lubben Social Network Scale−6; loneliness, with the short‐form UCLA Loneliness Scale. Objective and subjective measures of cognitive impairment included the Mini‐Mental State Examination and a single‐item self‐rating of cognitive health.

Result

In the logistic regression model for objective cognitive impairment, social isolation was significantly associated, but loneliness was not. In the model for subjective cognitive impairment, both social isolation and loneliness were significant factors. However, the effect of social isolation became non‐significant when loneliness was considered, suggesting a potential mediating role of loneliness. The subsequent mediation analysis confirmed that the indirect effect of social isolation on subjective cognitive impairment through loneliness was significant (B = .33, SE = .04, 95% CI = .24, .42).

Conclusion

Our analyses provide evidence for the proposed mediating effect of loneliness in the relationship between social isolation and subjective cognitive impairment. Intervention efforts should focus on reducing feelings of loneliness experienced by older immigrants, possibly by engaging them in socially meaningful and cognitively stimulating activities.
Qualitative study of how care is planned and delivered to people living with dementia and a long‐term condition
Authors: Rees Jessica , Walters Kate , Burton Alexandra , Cooper Claudia
Published: February 2022

Background

Dementia rarely travels alone. In the UK, almost 8 in every 10 people with dementia have another chronic condition. Long‐term conditions require continuous management in primary care, including support for self‐management. Tailoring physical health care plans to account for dementia is vital and requires skill and confidence from health care professionals. The objective of this study was to understand how care is planned in primary care, and how professional advice is followed at home, when a person has dementia and a long‐term condition.

Method

We conducted a remote ethnographic study, beginning in September 2020, using qualitative interviews, participant observations supplemented by care plan document analysis and event‐based diaries. We invited people with dementia and their family carers, and relevant health and social care professionals and/or home care workers involved in care of long‐term conditions to participate. We used inductive thematic analysis to analyse observations and interviews and integrated the findings with document analysis to ensure data triangulation.

Result

Preliminary findings indicate a degree of disconnect between participant account of health care and documented medical notes, specifically between the ‘goal setting’ and ‘action planning’ aspects of care planning. Participants discussed the impact of the pandemic and reduced physical contact with primary care; in addition to aspects of holistic health management such as the closure of swimming pools. We consider how relationships between participants and general practitioners, homecare workers, and pharmacists are constructed within the care networks of people living with dementia and how these have shifted during the pandemic. We will present our reflections on conducting remote observations with people with dementia, including challenges of developing trust over the phone and overcoming technology barriers.

Conclusion

Continued involvement of people with dementia in healthcare and in research is imperative despite the challenges of remote contact. Special consideration is required for people with dementia who lack capacity to ensure proxy management by family or home care workers does not become primary management.
A comparative study of 18F‐FDG PET brain metabolism and cognitive performance between normal controls and amnestic Alzheimer’s disease patients
Authors: Demey Ignacio , Falasco German , Mendez Patricio Alexis Chrem , Urrutia Leandro , Bérgamo Yanina , de Leon Magdalena Ponce , Sevlever Gustavo , Allegri Ricardo Francisco , Vazquez Silvia
Published: February 2022

Background

18F‐fluorodeoxyglucose Positron Emission Tomography (18F‐FDG PET) allows the measurement of brain metabolism in vivo. In neurodegenerative diseases, hypometabolism´s topography patterns usually correlate with certain types of cognitive dysfunction. In the amnestic presentation of Alzheimer’s Disease (AD), the temporoparietal hypometabolism is the typical 18F‐FDG PET signature. However, much less is known about its spatial correlation with other cognitive manifestations typically seen in the clinical setting. Objectives: To compare the distribution of 18F‐FDG PET between Normal Controls (NC), patients with Mild Cognitive impairment due to AD (MCI‐AD), and patients with AD Dementia (ADD) and to analyze each cognitive test as a covariate.

Method

Cross‐sectional study, including 14 NC (13 PET‐PIB ‐, 1 PET‐PIB +), 25 MCI, and 28 ADD patients, (all PET‐PIB +) matched by age and education. Images were normalized to a template using non‐linear methods. The metabolic differences between the 3 groups were evaluated by a voxel‐wise analysis based on Statistical Parametric Mapping. Statistical models were applied using neuropsychological tests as covariates, and VOIS statistics were generated using the Boogle‐DKT atlas.

Result

Differences were observed between the groups analyzed in middle and inferior temporal, posterior parietal, posterior cingulate, and precuneus cortical regions, among other areas of interest (p <0.005). Some of these areas correlated with a worse performance in verbal episodic memory tests (left temporoparietal regions), visuospatial tests (right parietal regions) and phonological fluency tests (left frontal and temporoparietal regions), among other results (p<0.005).

Conclusion

In this study, 18F‐FDG PET voxel‐wise analysis showed metabolic differences between the groups included, following the severity spectrum of each amnestic AD stage considered. Although these differences correlated with some cortical areas usually reported as the “AD metabolic signature”, some cortical regions were associated with cognitive functions that weren´t previously reported, allowing a better understanding of the cortical networks involved in the clinical manifestations of AD.
The connection between Down syndrome and Alzheimer disease
Authors: Battaglino Lisa B , Rodrigues Ashley B
Published: February 2022

Background

Individuals with Down syndrome (DS) face unique aging issues. Often the serious consequences of Alzheimer’s disease in individuals with DS are misunderstood and inadequately addressed due to a lack of understanding and sparse resources. This presentation explores research in medical advances, education, programming, housing, and transitioning.

Method

This presentation is a review of literature and research examining the relationship between Down syndrome (DS) and Alzheimer's disease.

Result

Over the past 40 years the life expectancy of people with Down syndrome has more than doubled from 25 years in 1983 to 60 years in 2020 due to advances in cardiac surgery, medications, updated treatments, and the elimination of inhumane institutionalization. As a result, ever increasing numbers of people deal with the issues faced when people with DS experience premature age related changes. While memory loss is an early predictor of AD in the general population, according to the Alzheimer’s Association (2020) people with DS are more likely to experience other symptoms such as a reduction in being social, decreased enthusiasm for usual activities, a decline in focusing ability, sadness, fearfulness or anxiety, irritability, uncooperativeness or aggression, sleep disturbances, adult onset seizures, changes in coordination, and or increased excitability.

Conclusion

Implications for professionals include becoming knowledgeable of the signs of AD in clients with DS. Essential to the planning and implementation of effective medical interventions as well as programing is the development of medications, strategies and behavioral supports to ease transitions, the creation of resources for families and care givers, and the recognition of the growing demands of older adults with DS. Families are frequently ill prepared for the increased demands put upon them as a result of AD symptoms in their loved one with DS. Accessing state, federal, and privately funded services may be unknown, unavailable, and/or difficult. In addition, proper diagnosis and reliable information may not be readily available. These families are often in dire need of sound medical advice, financial, emotional, respite care, and physical assistance.
Comparison of Pittsburgh compound‐B and flutemetamol white matter binding
Authors: Zeydan Burcu , Schwarz Christopher G. , Przybelski Scott A. , Lesnick Timothy G. , Kremers Walter K. , Senjem Matthew L. , Kantarci Orhun H. , Min Paul H. , Kemp Bradley J. , Jack Clifford R. , Kantarci Kejal , Lowe Val J.
Published: February 2022

Background

White matter (WM) 11C‐Pittsburgh compound‐B (PiB) and 18F‐Flutemetamol (FMT) uptake is increasingly being used as a reference region to calculate the standard uptake value ratios (SUVr) in longitudinal amyloid‐β PET studies. PiB uptake is lower in WM hyperintensities (WMH) in older adults. Furthermore, WM PiB uptake increases with aging. Our objective was to determine whether a similar variation in WM uptake exists with an 18F‐ligand FMT.

Method

A cohort of cognitively unimpaired (CU) older adults with median (range) age of 67 (61, 83) years (N=31), and younger adults with median (range) age of 38 (30, 48) years (N=30) from the community responding to a study advertisement underwent MRI, PiB and FMT PET. MRI‐FLAIR images were segmented into WMH and normal appearing white matter (NAWM) and registered to the T1‐weighted image. PiB and FMT PET images were registered to the T1‐weighted image. PiB and FMT SUVrs from the WMH and NAWM compartments were calculated using cerebellar crus uptake as a reference.

Result

WMH PiB SUVr and NAWM PiB SUVr were lower in the younger compared to the older adults (p<0.001). WMH FMT SUVr and NAWM FMT SUVr were lower in younger compared to older adults (p<0.001). PiB SUVr was lower than FMT SUVr both in younger and older adults in both WMH and NAWM compartments (p<0.001). In both age groups, PiB SUVr and FMT SUVr in WMH was lower than NAWM (p<0.001). AUROC analysis demonstrated no difference between PiB versus FMT SUVr in differentiating WMH from NAWM in younger and older adults.

Conclusion

WMH and NAWM SUVRs are higher with FMT than PiB, however both PiB and FMT show a similar topographic pattern of uptake in the WM with higher uptake in NAWM compared to WMH. Aging is associated with a decrease in myelin integrity and increase of WMH volume. Higher WMH and NAWM PiB and FMT uptake in the older compared to younger adults suggests that additional aging‐related mechanisms are influencing WM PET tracer uptake. Age and WMH volume should be considered when WM uptake is used as a reference region for the evaluation of cortical uptake of both PiB and FMT.
Caring for behavioral symptoms of dementia (CBD): A new investigation into cannabidiol for the treatment of anxiety and agitation in Alzheimer’s dementia
Authors: Ash Eleanor T , McManus Kaitlin R , Smith Rosemary , Harper David G , Gruber Staci , Forester Brent P
Published: February 2022

Background

Anxiety and agitation symptoms affect 25‐70% of the dementia population, though there are no FDA‐approved medications that treat the behavioral symptoms of AD. Thus, the need for developing safe and efficacious treatments for anxiety and agitation in AD is dire. One potential treatment is cannabidiol (CBD), the major non‐intoxicating constituent of cannabis sativa, a variety of the cannabis plant that contains <0.3% delta9‐tetrahydrocannabinol (THC), the main intoxicating constituent in cannabis, by weight. The present open‐label clinical trial seeks to address this gap in knowledge by assessing the efficacy and tolerability of a high‐CBD/low‐THC sublingual solution as a treatment for anxiety and agitation in older adults with Alzheimer’s disease.

Method

An 8‐week open‐label clinical trial of an industrial hemp‐derived high‐CBD/low‐THC sublingual solution. This includes 12 research participants with AD and symptoms of anxiety with or without agitation. Our primary efficacy outcome measures include the anxiety domain of the Neuropsychiatric Inventory‐Clinician Version (NPI‐C) and the Generalized Anxiety Disorder‐7 Item Scale (GAD‐7). Our secondary safety outcome measures include monitoring for serious adverse events and medication side effects, cognitive decline estimates from the Mini Mental Status Exam (MMSE), and the emergence of possible delirium from the Confusion Assessment Method (CAM). Scores on the NPI‐C, the Cohen‐Mansfield Agitation Inventory (CMAI), and caregiver burden estimates from the Zarit Caregiver Burden Interview will be included as additional exploratory measures.

Results

We hypothesize that twice daily treatment with a high‐CBD/low‐THC solution in older adults with AD for 8 weeks will be associated with a statistically significant reduction in anxiety and agitation symptoms compared to baseline, as measured by our efficacy outcome measurements. We predict that the solution will be well‐tolerated by the study population, as measured by our safety outcome measurements.

Conclusion

With no current FDA‐approved treatments for these behavioral symptoms, patients with AD risk ineffective therapies or mortality‐associated antipsychotic treatments to address their NPS. Treating anxiety and agitation in these patients not only alleviates their symptoms but could also reduce caregiver burden and lengthen the time to institutionalization. CBD is a promising anxiolytic treatment that could advance our available treatment options for anxiety and agitation in AD.
Lesion‐network mapping of tau accumulation is predictive of domain‐specific cognitive deficits in Alzheimer’s disease
Authors: Luan Ying , Franzmeier Nicolai , Rubinski Anna , Ewers Michael
Published: February 2022

Background

Clinical heterogeneity is present in a substantial portion of patients with Alzheimer’s disease (AD). Understanding the underlying pathological differences is an unmet goal towards patient‐tailored medicine in AD. We hypothesized that the brain localization of tau deposition, a key driver of neurodegeneration, is predictive of which cognitive domain predominantly affected. We adopted a symptom‐network mapping approach applied to tau PET, reasoning that the functional connectivity of local tau PET to a cognitive‐domain specific network is predictive of which cognitive ability is impaired.

Method

We included 448 participants consisting of 234 amyloid‐PET‐negative cognitively normal subjects (CN‐Aβ‐), 95 amyloid‐PET‐positive mild cognitive impairment (MCI‐Aβ+) and 119 amyloid‐PET‐positive cognitively normal (CN‐Aβ+) patients. AV1451 tau‐PET was parcellated using the 400 ROI Schaefer atlas. Adopting a lesion‐network mapping approach (Darby et al. Brain 2018), we computed in the Aβ+ participants, subject‐level W‐scores, i.e. the standardized deviation of tau‐PET ROI values from those in CN‐Aβ‐. We computed for each subject and tau‐PET lesion (ROI W‐score > 2) the seed‐based connectivity based on resting‐state fMRI data from Human Connectome Project (n = 1000), rendering patient‐level lesion network maps. In order to identify symptom‐specific lesion‐networks, we regressed composite scores of episodic memory (ADNI‐MEM), executive function (ADNI‐EF), and language (ADNI‐LAN) onto the subject‐level lesion‐network maps, using partial least squares.

Result

Substantial variability in the tau‐PET lesions locations between subjects were observed (Figure 1A), with highest overlaps observed in the lateral and medial temporal cortex and posterior cingulate (Figure 1B). We found for each cognitive domain, a specific tau‐lesion network map: stronger connectivity of tau‐PET lesions to lateral temporal, posterior parietal and lateral prefrontal cortex were associated with lower episodic memory (ADNI‐MEM). In contrast, stronger connectivity to pre‐ and post‐central gyri and superior parietal cortex was associated with lower executive function (ADNI‐EF), and stronger connectivity to inferior frontal and auditory cortex was associated with language function, suggesting the presence of cognitive‐domain specific networks of tau lesions.

Conclusion

We identified functional network patterns of local tau PET accumulation that map onto impairment in specific cognitive domains. This approach thus contributes to precision medicine guided prediction of specific cognitive impairments in AD.
Recommendations of nursing students to improve nursing curriculum in Germany: Current results of a study with mixed methods design
Authors: Panjaitan Hentry , Kowe Antonia , Vogel Jann Niklas , Wachholz Anne , Teipel Stefan J
Published: February 2022

Background

Digitalization is key to face socio‐demographic change accompanied by an increasing care demand of people with dementia and a shortage of skilled healthcare workers. The project Digital Training of Nursing and Health Management (DigiCare) aims to involve people affected by dementia in the development of digital teaching formats that meet the needs of all stakeholders in dementia care. Here, we explored the needs of nursing students which already have practical experience in dementia care to identify gaps in the existing curricula and subjective improvement suggestions.

Method

We used a mixed methods design consisting of a quantitative survey with a questionnaire and semi‐structured qualitative interviews. We analysed the quantitative data descriptively and the qualitative data with qualitative content analysis approach according to Mayring.

Result

Seventeen nursing students took part in the quantitative survey (agemean = 37.1 years; male: 29.4%) and five nursing students were interviewed qualitatively (agemean = 38.0 years; male: 40.0%). Participants named nursing care especially dealing with challenging behaviour in dementia and care management as gaps in the existing curricula in nursing courses. Participants wished for a practical orientation of the course or an internship during the training. In their daily working routines, smartphones and computer were the most frequently used technological devices. Barriers to use technological devices in care were additional effort for nurses, mistrust among patients and loss of a close relationship to patients. Although participants saw blended learning concepts as an opportunity to improve their training, they criticised the lack of a contact person for specific questions on the implementation of digital learning.

Conclusion

The survey indicated that digital teaching methods in combination with a practical orientation of the curriculum could provide effective training in dementia care for nursing students. The existing doubts of nursing students about digital learning methods and the usage of technological devices must be taken into account when integrating new technologies into the curriculum and working routine.
Preliminary efficacy of an internet‐delivered behavioral intervention for insomnia in individuals with mild cognitive impairment
Authors: Mattos Meghan K , Manning Carol A , Quigg Mark S , Davis Eric M , Barnes Laura , Sollinger Ann , Ritterband Lee M
Published: February 2022

Background

Insomnia is present in up to 50% of older adults with cognitive impairment. When insomnia is left untreated, pre‐existing cognitive problems may be exacerbated and potentially contribute to further cognitive decline. One promising approach to improve cognitive health in individuals with cognitive impairment is to improve quantity and quality of sleep. Our objective was to determine preliminary efficacy of an Internet‐delivered cognitive behavioral therapy for insomnia program in older adults with mild cognitive impairment (MCI).

Method

Older adults with MCI and insomnia were recruited from hospital‐based memory and sleep disorders clinics and enrolled in a single‐arm intervention pilot study. Participants completed the Internet‐delivered, six‐part CBT‐I intervention over nine weeks with two‐week pre‐ and post‐assessments using self‐reported sleep diaries. Preliminary efficacy was informed by patient‐generated data on sleep parameters.

Result

Twelve participants enrolled and, on average, were 75.8 years of age with a 7.5‐year history of sleep difficulties. There were significant differences found on all pre‐ to post‐assessment sleep measures. Most notably, there were clinically meaningful changes in insomnia severity index (13.5 to 8.3, p<.01), sleep efficiency (77.3% to 86.5%, p<.001), wake after sleep onset (38.0 to 22.4, p=.02), and sleep onset latency (36.0 to 18.3, p<.001). There was no statistically significant change in cognitive measures over time (p>.05).

Conclusion

Results provide evidence that older adults with cognitive impairment can complete CBT‐I via the internet and achieve clinical improvements in their sleep.
Retinal microvasculature and neurodegenerative changes in males vs females with Alzheimer’s disease: A case‐control study
Authors: Mirzania Delaram , Thompson Atalie C. , Robbins Cason B. , Soundararajan Srinath , Liu Andy , Johnson Kim , Grewal Dilraj S. , Fekrat Sharon
Published: February 2022

Background

Women comprise two‐thirds of people living with AD, regardless of age and ethnicity. Retinal imaging is being increasingly investigated as a potential non‐invasive method to understand neuropathological and microvascular changes in AD. The purpose of this study was to evaluate differences among males and females in the superficial capillary plexus (SCP) of the retinal microvasculature in patients with Alzheimer’s disease (AD) compared to age‐matched cognitively healthy controls.

Method

Prospective cross‐sectional study of participants ³50 years of age with a diagnosis of AD compared to cognitively healthy controls who underwent optical coherence tomography OCT angiography (OCTA). The foveal avascular zone area (FAZ) and vessel density (VD) and perfusion density (PD) in the 3 and 6‐mm circle and ring using EDTRS overlay were calculated.

Result

Two hundred and two eyes (101 cases, 101 controls) were included. No significant sex differences were found in the AD or control cohorts in regard to VD or PD. Central subfield thickness (CST) and FAZ area were not different between male and female AD. Among controls, males had a thicker CST (p < 0.001) and smaller FAZ area (P=0.003). Retinal nerve fiber layer (p > 0.05) and ganglion cell layer (p=0.054) thicknesses were similar among male AD, female AD, and controls.

Conclusion

There may be a loss of the physiologic sex‐related differences in retinal structure and microvasculature in AD compared to controls. Further studies are needed to elucidate the pathophysiological basis for these findings.
Amyloid and tau PET in a middle‐aged, racially and ethnically diverse, community‐based cohort
Authors: Lao Patrick J. , Berroa Joncarlos , Benavides Andrea , Tejeda Emely , Shouel Heather , Igwe Kay , Maas Benjamin , Schupf Nicole , Mayeux Richard , Manly Jennifer J. , Brickman Adam M.
Published: February 2022

Background

Alzheimer’s disease (AD) pathophysiology (i.e., amyloid and tau) develops first and then leads to subsequent neurodegeneration and cognitive impairment. Anti‐amyloid or anti‐tau interventions would be most effective in the earliest stages of disease, prior to irreversible neuronal death, i.e., during midlife. Our objective was to characterize the patterns of distribution for amyloid and tau PET in a middle‐aged, racially and ethnically diverse sample.

Method

In an ongoing study, participants (63±6 years old, 73% women, 19±5 years of education, 8 Non‐Hispanic White/21 Non‐Hispanic Black/47 Latinx) underwent amyloid PET imaging with Florbetaben (n=76; weighted average SUVR in Thaal phase regions) and tau PET imaging with MK‐6240 (n=59; average SUVR in Braak stages I‐VI) in the Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease. Amyloid positivity was considered at >1.25 global SUVR, while tau positivity was considered at >2SD above the mean in Braak stage I in an independent healthy sample. A series of general linear models on the region of interest and voxel level were performed to determine the associations among age, amyloid, and tau PET.

Result

Regional patterns of amyloid and tau burden were similar across race/ethnicity groups (Figure 1). In our middle‐aged sample, 13% were amyloid positive, while 7% were tau positive in Braak stage I. Amyloid positivity was observed as early as 60 years old and tau positivity was observed as early as 62 years old. Older age was associated with increased global amyloid (r=0.36, p=0.001), but was not associated with tau burden in any Braak stage. Using amyloid continuously, increased global amyloid was associated with increased tau in Braak stage I (r=0.25, p=0.06), but not with tau in Braak stages II‐VI after adjusting for age. Using amyloid dichotomously, tau burden was higher in amyloid positive compared with amyloid negative individuals in Braak stages I‐V after adjusting for age (p<0.04; voxelwise results in Figure 2).

Conclusion

Preliminary data suggest a range of AD pathophysiology during midlife in a racially and ethnically diverse sample. Amyloid increased in an age‐dependent manner, while tau increased in an amyloid‐dependent manner suggesting that the amyloid cascade begins in midlife.
Translating magnetic resonance imaging research in clinical practice for dementia: The Oxford Brain Health Centre
Authors: Griffanti Ludovica , Clare O'Donoghue M. , Blane Jasmine , Mitchell Robert , Aikin Nicola , Lindsay Karen , Campbell Jon , Semple Juliet , Nobis Lisa , Raymont Vanessa , Martos Lola , Mackay Clare
Published: February 2022

Background

The Oxford Brain Health Centre (BHC) is a pioneering psychiatry‐led joint clinical‐research service launched in 2020. It provides NHS patients with existing memory problems access to high‐quality assessments not routinely available in clinical practice, including MRI rather than CT. This abstract describes the MRI protocol of the BHC, designed to translate dementia research advances into clinical practice, and shows preliminary data from the BHC pilot.

Method

The BHC MRI protocol (details in Table 1) is structured to include core clinical sequences (high‐resolution T1, FLAIR, SWI and 3D DWI) and optional research sequences (TOF, ASL, DWI, resting state fMRI). Patients can consent to use of clinical scans for research, additional research sequences, and recontact about future research. Sequences were matched as much as possible to the UK Biobank (UKB) imaging protocol (Miller et al., 2016 Nat Neurosci.) to take advantage of its high‐quality data, clinically feasible acquisition time, and availability of big population data. Additional scans on healthy controls are planned to improve generalizability of UKB and enrich the age range of interest.

Result

Thirty‐three patients attended the BHC between August and December 2020 (average age 77.5 years, age range 66‐90 years, 58% female). 94% of patients completed the clinical scans and consented use for research, 64% consented to additional research sequences and 42% completed the research scan. Table 1 details the number of currently available scans for each modality. An adapted version of the UK Biobank pipeline (Alfaro‐Almagro et al., 2018 Neuroimage) is being developed to extract quantitative measures from the scans (imaging derived phenotypes, IDPs). For example, Figure 1 shows how hippocampal volumes for 11 BHC patients compare with UKB data: most of them fall in the lower percentiles, suggesting potentially pathological deviations from the norm.

Conclusion

The data acquired in the first months of the BHC pilot phase demonstrate that the MRI protocol is well tolerated and provides good quality data both for research and clinical purposes. Future work aims to integrate quantitative measures in the radiology reports of the BHC and evaluate their impact in the clinical practice.
The effect of memantine on cortical network function in frontotemporal lobar degeneration is conditional on baseline GABA physiology
Authors: Perry Alistair , Adams Natalie E. , Hughes Laura , Kocagoncu Ece , Rouse Matthew A. , Murley Alexander G. , Bevan‐Jones W. Richard , Passamonti Luca , Street Duncan , Naessens Michelle , Holland Negin , Nesbitt David , Cope Thomas E. , Rowe James B.
Published: February 2022

Background

Frontotemporal lobar degeneration (FTLD) is associated with deficits to GABA and glutamatergic neurotransmitters, particularly in the frontal cortex. While targeting GABAergic systems has shown to restore frontotemporal deficits in FTLD, little is known whether pharmacological probes of glutamatergic functioning have similar effects in these circuits.

Method

Twenty participants with a FTLD‐associated syndrome (11 with PSP, 9 with bvFTD) and 20 healthy‐controls undertook two magnetoencephalography (MEG) sessions with a roving auditory oddball paradigm assessing frontotemporal change detection: (1) session on placebo and (2) after 10mg of oral memantine, which aims to blocks glutamatergic ecotoxicity. The mean amplitude of MEG “mismatch negativity” responses (MMN; standard‐deviants, 125‐175ms) was calculated across gradiometer sensors and for bilateral frontotemporal sources. Glutamate and GABA levels were measured using 7T proton magnetic resonance spectroscopy of the right inferior frontal gyrus (IFG). Frequentist and Bayesian ANOVAs assessed the differential mean MMN responses between controls and patients across placebo and drug conditions. Evoked difference waveforms (standard‐deviants) across the peristimulus time‐window were analysed using random field theory (RFT) (crit p=0.05, FWER) for the interaction effects of interest (i.e. drug session x group and drug x MRS levels).

Result

Patients and controls did not demonstrate differential mean MMN amplitudes on placebo at the average‐sensor (p=0.95) or source‐level (p>0.27) (BF10=0.3‐0.5). Across sensors, only controls exhibited a differential drug‐dependent MMN, reflected by a steeper rebound of difference waveforms between 206‐288ms on memantine (Fig 1A; pFWER=0.026, cluster‐level). However, no interaction was found for mean MMNs (p>0.053). Notably, RFT (Fig 1B) and linear mixed models (Fig 1C) identified that greater GABA levels in patients are significantly associated with stronger MMN responses in right‐hemisphere areas under memantine. Glutamate levels did not moderate the mean MMN response to memantine (p>0.065).

Conclusion

Overall, we show that targeting glutamatergic systems may not lead to a restoration of frontotemporal physiology across patients. However, the effects of memantine are conditional on patient's baseline GABA, suggesting a critical balance between glutamatergic and GABA physiology that may underlie the large‐scale neural deficits in FTLD.