bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia, fall risk and routine clinical care: An opportunity to enhance care by incorporation of examiner independent computerized cognitive testing
Authors: Kaczmarek Olivia , Rosenfeld Yulia , Chee Jordan , Bumstead Barbara , Zarif Myassar , Anand Bhupinder , Ofori Edward , Gudesblatt Mark
Published: February 2022

Background

Dementia is an encompassing term referring to multiple clinical conditions characterized by progressive cognitive impairment (CI) that interferes with an individual’s ability to function independently. Clinically, CI varies in degree and combination of cognitive deficits from memory loss, verbal impairment, apraxia to impaired executive function. Clinician recognition of such varied types/degrees of CI is likely problematic. Falls are common and their consequence costly in individuals with such cognitive impairment. Effective analysis of multiple aspects of cognitive function can be provided in routine care with a validated, examiner independent, sensitive and reliable computerized cognitive assessment battery, (CAB, Neurotrax) which specifically evaluates multiple cognitive domains (CD): Memory (MEM), Executive Function (EXE), Visual Spatial (VIS), Verbal Function (VER), Attention (ATT), Information Processing (INF), and Motor Skills (MOT) and a Global Cognitive Summary Score (GCS).

Method

Cross sectional analysis of PwDaD who underwent standardized CAB cognitive testing and were also screened for risk of falls based on number of falls in the past and persons fear of falling.

Result

120 PwDaD, 57.5% female, average age 74 +/‐ 10 years. T‐tests were performed between CAB CD scores grouped by risk of falling (high/low). The following CD scores were associated with increased fall risk: GCS (p=<.05) and VIS (p=<.05). A significant increased fall risk was also associated with an accumulative CDI (# of individual cognitive domains impaired) (p=<.05).

Conclusion

As CAB measured cognition decreases PwDaD risk of falling increases. PwDaD at increased risk for falls had increased accumulative CI with an average of 3 CDI. PwDaD also at increased risk for falls have significantly lower GCS and Visual Spatial scores. Earlier identification of increased fall risk might allow clinicians an opportunity to effectively and pre‐emptively intervene to reduce such increased disability consequence and costs associated with this disease related impact.
Qualitative study of frontotemporal lobar degeneration caregivers' coping strategies and concerns during COVID‐19
Authors: Martinez Maria , Tartaglia Maria Carmela , Cacchione Elena , Monteiro Marta , Maboudi Mehrdad , Ragnanan Tracey
Published: February 2022

Background

The coronavirus (COVID‐19) pandemic has been particularly arduous on those living with dementia and their caregivers as they depend on in‐person support and programs. High rates of depression and anxiety were reported in Alzheimer's disease during the COVID‐19 pandemic (El Haj, 2020). In patients with frontotemporal lobar degeneration (FTLD) there are additional challenges as these patients have motor, language, behavior disorders and cognitive deficits. We examined the impact of COVID‐19 on FTLD caregivers.

Method

From March 2020‐June 2020, we carried out a qualitative study with FTLD caregivers to determine the impact of COVID‐19 on their continued ability to care for the person with dementia. We examined the following: patient’s age, relationship to primary caregiver, number of people in household, access to virtual telecommunication, access to exercise, caregivers’ greatest supports, their identified needs and fears.

Result

We included 52 FTLD patient‐caregiver dyads (5 behavioral variant (bvFTD), 17 primary progressive aphasia (PPA), 19 Corticobasal Syndrome (CBS), and 11 Progressive Supranuclear Palsy (PSP)). Mean age of patients was 67.9+/‐8.76. 57% of caregivers were female. 60% of patients lived alone with spouse, 23% lived with spouse and a child, 2 patients lived in LTC, 3 with a family member (not spouse) or friend, 1 was in hospital, and 2 lived alone. 75% had access to virtual telecommunication. 44% were engaged in physical activity (mostly walking). 16 caregivers (25%) reported their greatest needs were reinstating or increasing Personal Support Worker hours, 8 (15%) needed access to other health care providers and for 7 (13%) they wanted Adult Day Programs to reopen. 31 caregivers (60%) reported their greatest support was family; 8 (15%) were grateful for community supports. 22 caregivers (42%) were concerned about ongoing decline whilst only 11 (21%) feared COVID.

Conclusion

We provide some qualitative data on FTLD caregivers’ experience during COVID. The most frequent concern was ongoing decline. Over 50% of caregivers reported their greatest need was access to services and their greatest support was family network. Enabling easily accessible and safe in‐home care is important to support people living at home with FTLD during the pandemic. REFERENCES: El Haj, M. Psychiatry Research, (2020).
Associations of hippocampal cholinergic receptor binding and subcortical cerebrovascular disease with whole brain volume in cognitive aging and AD
Authors: Lim Aaron C. , Sultzer David L , Gordon Hailey L. , Melrose Rebecca J.
Published: February 2022

Background

Alzheimer’s Disease (AD) is associated with compromise to the cholinergic system. Using PET ligand imaging, our group has reported reduced nicotinic cholinergic receptors (nAchR) in the hippocampus in AD relative to cognitively unimpaired older adults. Studies have increasingly identified that chronic ischemic cerebrovascular disease (CVD) serves as a risk factor for neurodegeneration, and also directly correlates with B‐amyloid and tau accumulation (Flaherty et al., 2020; Wei et al., 2019). We sought to determine the unique contributions of cholinergic dysfunction and CVD to brain health in cognitive aging. We therefore tested differential contributions of T1 white matter hypointensities and hippocampal nAchR binding in predicting whole brain volume among individuals with varying levels of cognitive impairment.

Method

84 individuals (clinical Alzheimer’s Disease (AD), n=27; Mild Cognitive Impairment (MCI), n=25; and Cognitively Unimpaired (CU), n=32) completed MRI and 2‐18F‐fluoro‐3(2(S)azetidinylmethoxy) pyridine (2FA) ‐PET imaging sessions. Total Brain Volume, excluding cerebellum, brain stem, and ventricles, was calculated using FreeSurfer. SPM was used to generate nAchR binding estimates using anatomical ROI of bilateral hippocampus.

Result

When covarying for diagnostic group, age, and use of cholinesterase inhibitors, hierarchical linear regressions identified a significant association between hippocampal nAchR binding and total brain volume (B(SE)=.013(.003); p<.001), while the association between white matter hypointensities and total brain volume was not significant (B(SE)=‐.99(.84); p=.24). Stratified by group, the same pattern emerged in a combined sample of clinical AD and MCI (nAchR binding B(SE)=.013(.005); p<.01, hypointensities B(SE)=‐.18(.91); p=.84). In CU, however, white matter hypointensities were negatively associated with total brain volume (B(SE)=‐10.60(3.53); p<.01), while the relationship between hippocampal nAchR binding and total brain volume was not significant (B(SE)=.006(.005); p=.26).

Conclusion

White matter hypointensities are associated with a measure of brain health among CU; such vascular risk factors may be important to track in preventative treatment. Hippocampal cholinergic function, relative to hypointensities, may be more closely aligned with brain health among those with cognitive decline. Longitudinal study of vascular and cholinergic systems and their interactions are warranted; corroboration of these findings in longitudinal studies may elucidate different treatment targets across stages of AD.
Racial differences in dementia‐related pathology underlying cognitive decline: The Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Hughes Tim M. , Schaich Christopher L. , Lockhart Samuel N. , Hiatt Kevin , Whitlow Christopher T. , Jung Youngkyoo , Bertoni Alain , Burke Gregory L. , Solingapuram Sai Kiran K. , Heckbert Susan , Craft Suzanne , Rapp Stephen R. , Hayden Kathleen M.
Published: February 2022

Background

Racial differences in dementia‐related pathology are purported to underlie health disparities in Alzheimer’s disease and related disorders. We examined the prevalence and relevance of neuroimaging biomarkers of cerebral small vessel disease (cSVD), and β‐amyloid (Aβ) deposition in cognitive decline and impairment among a diverse cohort of older adults.

Method

Participants at the Wake Forest MESA site were recruited at Exam 6 (2016‐19) to receive additional detailed cognitive testing, cognitive adjudication, and multimodal neuroimaging. Brain MRI on 3T Siemens Skyra, included T1, SWI, FLAIR and NODDI sequences. Total gray matter and white matter hyperintensities (WMH) volumes were adjusted for intracranial volume. A single neuroradiologist graded vascular lesions, including cerebral microbleeds, large and lacunar infarcts. Cognitive decline was measured by the Cognitive Abilities Screening Instrument (CASI) at Exam 5 (2010‐12) and Exam 6 (2016‐19). A subset of 157 participants completed Aβ‐PET at Exam 6 to quantify Aβ burden and positivity (PiB SUVR ≥1.21). Multivariable linear and logistic regression modeled neuroimaging parameters with change in CASI and cognitive status adjusted for age, gender, education, and APOE genotype, considering potential interactions by race.

Result

The imaging sample included 252 participants (53% African‐American and 47% White; aged 72±7 years; 58% women, Table 1). 27% of participants were adjudicated to have mild cognitive impairment (MCI) and 4% had dementia. Aβ positivity (36%) and cSVD (microbleeds in 37% and lacunes in 32%) were common and did not differ by race. Further, temporal lobe cortical thickness and WMH volumes did not differ by race. Lower total gray matter volume, higher WMH volumes, and lower temporal lobe cortical thickness were consistently associated with greater cognitive decline and impairment across racial groups (Table 2). Significant interactions between race and imaging biomarkers with cognitive decline and impairment observed for: greater NODDI Free Water only in White participants and microbleeds and Aβ only in African‐American participants.

Conclusion

Imaging biomarkers indicative of cSVD and Aβ are common in older adults. These biomarkers were not more prevalent in African‐American than White older adults as previously reported; however, they appear to be more strongly related to cognitive decline and impairment among African‐Americans.
Exploratory cross‐sectional mediation analysis of the dual‐task effect of cognition on gait in individuals with memory loss
Authors: Delgado Ferdinand , Kaczmarek Olivia , Trebing Stacy , Zarif Myassar , Gudesblatt Mark , Ofori Edward
Published: February 2022

Background

Memory loss is one of the hallmark symptoms of cognitive impairment that progresses towards dementia. Different cognitive domains (CD) have been suggested to influence the performance of dual‐task (DT) activities. While there is evidence of DT effects on those with mild cognitive impairment and other dementias, the impact of DT on those with subjective memory loss is unknown.

Method

Participants (n=57; mean age: 72.72±10.56 years) with memory loss but without a diagnosis of cognitive impairment, dementia, or other neurodegenerative diseases were included. They performed validated computerized cognitive assessment battery (CAB, NeuroTrax BrainCare) to obtain CD measures of executive function (EF), attention, memory, visual‐spatial processing (VSP), information processing speed (IPS), and a global cognitive score (GCS) measure. Using the Zeno Walkway Gait Analysis System (Protokinetics), measures of velocity, stride width (SW), stride time (ST), stride length, cadence, double support (DS), and gait variability were obtained for both single‐task and DT gait. Participants chose between performing the DT gait by either recalling names (n=14), counting backward by 3’s (n=16), or by 7’s (n=27), which were used as group assignments for analysis. A three‐group cross‐sectional mediation analysis was performed using standardized cognitive measures as mediators and the DT effect (DTE) of the gait parameters as outcomes of interest. Data analysis was conducted using SPSS 26 and SPSS AMOS 26.

Result

No significant mediators of cognition on the dual‐task effect of either task were identified. However, increases in individual CD significantly predicted improvement of DTE in specific gait parameters: (1) memory significantly predicted DTE stride time (Effect size by standardized beta(ES)=0.343,p=0.022) and DTE double support (ES=0.322,p=0.033); (2) GCS (ES=0.388,p=0.028), attention (ES=0.348,p=0.007), and IPS (ES=0.290,p=0.027) significantly predicted DTE stride width; and (3) Attention (ES=0.282,p=0.047) significantly predicted DTE cadence. Furthermore, between‐group analysis showed significant differences in VSP (F(2,54)=8.820,p<0.001), IPS (F(2,54)=3.350,p=0.043) and GS (F(2,54)=5.149,p=0.009).

Conclusion

Results suggest that individual CD (VSP, IPS, and/or GS) scores impact different aspects of dual tasking gait in individuals with memory loss. While there were no significant mediators, the significant cognitive predictors suggest improvement of those individual CD could improve the DTE of individual gait measures.
Perivascular spaces and cognitive performance in the Northern Manhattan Study
Authors: Gardener Hannah , Rundek Tatjana , DeRosa Janet , Levin Bonnie , Sun Xiaoyan , Wright Clinton B. , Elkind Mitchell S.V. , Sacco Ralph , Gutierrez Jose
Published: February 2022

Background

Perivascular spaces (PVS) are fluid‐filled compartments surrounding brain small blood vessels, serving as conduits for fluid transport, exchange between CSF and interstitial fluid, and clearance of waste products. PVS are visible on MRI and associated with cerebral small vessel disease (SVD), and research is needed to understand their role as markers of SVD and potential contributors to vascular cognitive impairment. PVS have been reported in Alzheimer's disease, but less is known regarding their association with cognition in diverse populations. We tested the hypothesis that PVS are associated with cognition, independent of demographics and other markers of SVD, including white matter hyperintensity volume, silent brain infarcts, and cerebral microbleeds.

Method

We included 1,201 participants from the prospective Northern Manhattan Study. PVS were identified as parenchymal hypointensities <3mm on axial T1‐weighted MRI without a hyperintense rim on T2‐weighted or FLAIR images, that followed the orientation of perforating arteries. A semiquantitative PVS score represented the degree of brain involvement (range=0‐28). Generalized linear models were used to assess associations with four cognitive domains (memory, executive function, processing speed, language) and global cognition (mean of domains) over two assessments carried out an average 6 years apart. Model 1 adjusted for demographics; Model 2 also included vascular risk factors; Model 3 also included burden of SVD.

Result

Among 1,201 participants (mean age=71±9 years; 60% women, 66% Hispanic, 18% Black, 10±5 years education; 68% with hypertension, 19% diabetes, 65% hypercholesterolemia), PVS scores ranged from 0‐22 with 55% having a PVS score >4. PVS score was not associated with global cognition z‐score at first neuropsychological assessment, nor change in global cognitive performance between the two assessments. Higher PVS score was associated with worse processing speed at first assessment in models 1 and 2 (Model 2 beta=‐0.015, p=0.01). A higher PVS score was associated with greater decline in memory, adjusting for demographics (model 1 beta=‐0.015, p=0.01), but this relationship was attenuated and not significant after adjusting for modifiable vascular risk factors.

Conclusion

PVS are prevalent and associated with worse processing speed independent of age and vascular risk factors. Vascular risk factors largely explained variability in the association between PVS and memory decline.
A subcortical variant of dementia with Lewy bodies?
Authors: Philippi Nathalie , Durand Hélène , Noblet Vincent , Botzung Anne , Blanc Frédéric
Published: February 2022

Background

Even though Dementia with Lewy bodies (DLB) is the second most frequent neurodegenerative disease after Alzheimer’s disease (AD), work is still needed on the definition of its clinical and radiological variants. The objective of the present work is to discuss the existence of a subcortical variant of DLB based on two previous studies. In the first study, the objective was to test the existence of a subcortical atrophy, contrasting with overall preserved cortex in DLB patients. In the second study, we described a series of DLB patients with an initial presentation including marked subcortical atrophy suggestive of normal pressure hydrocephalus (NPH).

Method

In the first study, we included 55 DLB patients and compared their cerebral volumes to those of 51 AD patients and to those of 17 matched healthy control subjects (CS). We examined the ratio of the total ventricular volume (TVV) against the total cortical volume (Cortex), extracted using freesurfer. In the second study, we retrospectively compared the profile of 21 DLB patients fulfilling the criteria of possible NPH on initial presentation, to those of 13 patients with probable NPH.

Result

In the first study, we found that DLB patients had a significantly higher TVV/Cortex ratio compared to both CS and AD patients. In the second study, we highlighted that some DLB patients have a clinical and radiological profile suggestive of NPH. DLB patients had a marked subcortical atrophy, with not significance difference in the dilatation of lateral ventricles and third ventricle compared to HPN patients, though they had a less acute callosal angle and less fourth ventricular dilatation.

Conclusion

DLB is characterized by a subcortical atrophy contrasting with relatively preserved cortex, so marked in some cases that it might evoke ventricular dilatation. Together the two studies suggest the existence of a subcortical variant of DLB, with a clinical presentation and marked subcortical atrophy suggestive of NPH.
Enhancing underrepresented group participation in aging research through workforce development of the Community Research Liaison
Authors: Lamas Anakaren , Vasconcellos Jennifer , Umpierre Mari , Sewell Margaret , Neugroschl Judith A , Chin Shehan , Goytia Crispin , Kinsella Michael T , Smith Nancy , Loizos Maria , McNamara Sarah , Brangman Sharon , Sano Mary
Published: February 2022

Background

Developing a workforce to best engage the breadth of the community in aging research requires highly trained individuals engaged in and trusted by underrepresented groups (URGs) and scientists in the research community. Researchers need to better understand how to engage with communities as partners to develop research proposals and recruitment strategies that motivate and sustain diverse participants.

We report on the initial phase of a dual‐site R‐24 (AG065163) to 1) develop a Community Research Liaison (CRL) job description 2) engage stakeholders in identifying candidates and 3) cultivate stakeholders as potential partners in future community and research engagement. The CRL will maximize research participation by fostering bi‐directional dialogue between URGs in the community and researchers to incorporate community feedback at the earliest stages of research development.

Method

Mount Sinai and SUNY Upstate conducted 4 listening sessions and 11 interviews with 46 individuals (20 community organization representatives, 16 researchers, 10 caregivers/seniors) who participated from July‐October 2020. Sessions, with open ended prompts, were conducted virtually, recorded and transcribed. Individuals were asked for input to optimize the job description and refine the scope of work. Data analysis was completed using thematic analysis.

Result

1) Scope: Some suggested narrowing the job description. Others noted that building trust entails creating linguistic/cultural congruence with multiple communities; therefore volunteers from diverse communities were suggested to support the CRL. 2) Finding candidates: Suggestions included reaching out to recent retirees or previous support group moderators. 3) Resources needed for researchers to recruit: These might include participant transportation and extra coordinator time. 4) Engaging stakeholders: All participants agreed to disseminate information and participate in future engagement activities. CRL candidates were referred. 5) Knowledge gaps: Researchers recognized the lack of URGs in research, however, one underscored that their focus was “on the science”, minimizing the importance of diverse recruitment.

Conclusion

The listening sessions positively impacted the design of the position description. By cultivating the stakeholders we were able to get referrals to interview for the CRL position. The CRL description will be a work in progress as the grant is implemented and real world experiences can be incorporated.
Beliefs about the COVID‐19 pandemic, trust in government, and vaccine intention in older adults with cognitive impairment in the United States and Italy
Authors: DeCaro Renee , Marin Anna , Vives‐Rodriguez Ana , Schiloski Kylie A , Hajos Gabor P , Di Crosta Adolfo , Ceccato Irene , La Malva Pasquale , Lahdo Naheer C , Donnelly Kaleigh , Dong Jiali , Kasha Sabrina , Rooney Colleen E , Dayaw Judith Nicole Tejada , Marton Gabrielle , Wack Audrey , Hanger Vanessa A , Domenico Alberto Di , Turk Katherine W , Palumbo Rocco , Budson Andrew
Published: February 2022

Background

The degree and spread of misinformation regarding the COVID‐19 pandemic has been prolific, influencing individuals of all ages. We examined belief in misinformation in older individuals with and without cognitive impairment in Boston, MA (United States) and Chieti (Italy). The purpose of this investigation was to compare the two cohorts on specific misconceptions, trust in media and government, perceived risk regarding COVID‐19, and their relation to COVID‐19 vaccine hesitancy and intention.

Method

Forty‐seven subjects from the U.S. (mean age = 75.4, SD = 9.4) and 134 subjects from Italy (mean age = 72.2, SD = 7.7) were administered a telephone neuropsychological battery and MoCA. One hundred twenty‐two individuals (67.4%) met the cutoff for cognitive impairment. Individuals answered a COVID‐19 Misinformation Questionnaire and Perceived Risk Scale. A Vaccine Hesitancy Scale was administered 4‐6 months after the initial assessment. Comparisons were made between the two cohorts using binary logistic regression, controlling for age, education, and cognitive status (i.e., MoCA).

Results

Individuals in the Italian cohort demonstrated greater perceived risk of contracting COVID‐19 and also greater trust in the government as a source of information. A large proportion of the sample (N=160; 88.4%) rated the media as not at all trustworthy. Greater cognitive impairment was predictive of misconception endorsement. Further, individuals in the U.S. cohort were approximately four times as likely as individuals in the Italian cohort to believe that that COVID‐19 was a bioweapon developed by a government or terrorist organization. Trust indices were not related to misconception belief. Examination of vaccine hesitancy, and confirmation of the preliminary analyses, will be undertaken following completed recruitment and testing.

Conclusion

When individuals hold knowledge that is incorrect, the consequences can be manifold. From our preliminary analyses, we found that trust in government was not related to misconception endorsement; however, differences emerged between the U.S. and Italian cohorts. This examination provides a broad, cultural context to complex health beliefs, with specific implications for health behaviors such as vaccine intention, for individuals with and without cognitive impairment.
Basilar artery dilatation relates to Alzheimer dementia, particularly among APOE4 non‐carriers
Authors: Gurel Kursat , Serra Guillermo Polanco , Allende Antonio J. Spagnolo , Brickman Adam M. , Kreisl William Charles , Gutierrez Jose
Published: February 2022

Background

Brain arterial dilatation has been associated with higher risk of dementia and cognitive decline in population‐based studies. Whether the association is related to brain amyloid or tau, pathological hallmarks of Alzheimer disease, is uncertain.

Method

We analyzed existing and de novo data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) regarding participants’ demographics, hypertension, dementia status, APOE4 genotype. We used composite PET measures of gray matter regions of beta amyloid (AV‐45) and neurofibrillary tangles (AV‐1451). We obtain de novo cross‐sectional carotid and basilar artery diameters using axial T2 MRI sequences. For cognitive outcomes, we used the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog) and clinical dementia rating (ordinal CDR) scores. All models were adjusted for age, sex, years of education, APOE4 carrier status and hypertension

Result

We included 478 ADNI participants (56% men, mean age 77±7, 36% cognitively normal, 48 with mild cognitive impartment and 16% with dementia). Combined carotid and basilar artery diameters were not associated with ADAS‐13 cog score (B=0.07 per SD, P=0.46), ordinal CDR (B=0.13, P=0.32), amyloid (B=‐0.001, P=0.57) or tau (B=0.02, P=0.45). Stratifying by anterior versus posterior circulation artery showed that basilar artery diameters, but not carotid diameters, were associated with a higher ADAS‐13 cog score (B=0.17, P=0.01), higher CDR (0.25, P=0.009), but not with amyloid (B=0.01, P=0.46). The association between basilar artery diameters and CDR was stronger among APOE4 non‐carriers (B=0.37, P=0.004) than in carriers (B=0.05, P=0.70, P for the interaction 0.12).

Conclusion

Brain arterial dilatation is associated with poorer cognitive outcomes, and the association is stronger among APOE4 negative participants. Investigation of how brain arterial dilatation relates to dementia and whether such relationship interacts with amyloid and/or tau may reveal novel aspects of the vascular contributions to dementia.
Piecing it together: Relationships between hippocampal subfields and cognitive impairment along the Alzheimer’s disease spectrum
Authors: Christopher‐Hayes Nicholas J , Embury Christine M , Wiesman Alex I , May Pamela E , Schantell Mikki D , Johnson Craig M , Wolfson Sara L , Murman Daniel L , Wilson Tony W
Published: February 2022

Background

The ability to form hippocampal‐dependent memories declines steadily in normal aging, and exponentially in people with probable Alzheimer’s disease (AD). Correspondingly, the whole hippocampal formation follows the same trajectories of decline. Critically, pathological changes to distinguishable hippocampal subfields and related cognitive abilities are not well characterized in. Herein, we investigated how these hippocampal subfield and neuropsychological memory measures interact.

Method

Structural MRI and neuropsychological data were collected from 29 biomarker‐confirmed individuals on the AD spectrum (ADS) and a comparison group of 17 biomarker‐negative healthy adults to examine the interactions between subfield‐specific hippocampal integrity and cognitive markers. Cognitive assessments included the Wechsler Logical Memory (WMS‐IV) and Hopkins Verbal Learning (HVLT‐R) tests. High resolution hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured from a dedicated T2‐weighted MRI slab of the hippocampi (TSE; 0.4 x 0.4 x 2.0 mm), co‐registered to a routine T1‐weighted MRI (MPRAGE; 1.0 x 1.0 x 1.0 mm), using automated hippocampal subfield segmentation (ASHS) software and the UPENN atlas consisting of scans of MCI individuals and older adults (Yushkevich et al., 2015). We performed a cross‐sectional analysis of the relationship between hippocampal subfield volume and behavioral performance on measures of learning and declarative memory. Relationships between hippocampal subfields and neuropsychological subtests were probed using multivariate models contrasting ADS and controls, while controlling for age, education, and intracranial volume.

Result

We show that hippocampal subfield volumes robustly predict performance on subtests of WMS‐IV, but not HVLT‐R, regardless of group. Moreover, we report unique contributions of CA3 on learning, subiculum on recognition, and CA2 and CA3 on recall. By dividing the hippocampal formation into distinguishable subfields using ultra high‐resolution MRI, we further elucidate their contributions to ADS‐related neurocognitive declines in learning and memory.

Conclusion

Subfield‐specific atrophy in the human hippocampus may constitute a sensitive measure of neurocognitive decline in patients on the AD spectrum. These results suggest that the atrophy of specific hippocampal subfields selectively influence subprocesses of learning and memory, and that these measures may be used to better model disease trajectories among individuals on the Alzheimer’s disease spectrum.
Development of an indigenous functional assessment (IFA) tool
Authors: Sharma Nabina , Walker Jennifer D
Published: February 2022

Background

Functional decline is an essential criterion for the clinical diagnosis of dementia. Functional decline is assessed by activities of daily living, which consist of Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL). IADL (e.g., cooking, taking medications, handling finances) is more complex as it requires multiple cognitive processes whereas BADL (e.g., bathing, dressing and toileting) can be performed with the support of habits and routines. IADL are more likely to be vulnerable to the early effects of cognitive decline, thus being the first indication of cognitive deterioration. Various functional assessment tools are available to assess instrumental activities of daily living; however, there is no culturally appropriate functional assessment tool for the Indigenous population. As activities of daily living differ across cultures, the tool developed to assess activities of daily living in one culture cannot assess it in another culture. Also, the existing IADLs are influenced by gender and socio‐cultural factors. Thus, we aim to develop a culturally‐grounded functional assessment tool to be used in Indigenous communities.

Method

The study will use a community‐based participatory approach to develop a functional assessment tool. An Indigenous community advisory group will be engaged in the research process. A focus group will be conducted with the Indigenous and non‐Indigenous health service providers working with Indigenous communities and in‐depth interviews with the care partner. The qualitative data on the perspectives, personal and professional experiences of health service providers, and the care partner's lived experiences will be analyzed using community‐engaged thematic analysis with the community advisory group's volunteer. The developed tool will undergo several iterative processes from experts and community advisory groups to reach a consensus on the final tool.

Result

We are establishing relationships with the Indigenous communities as a partner which is an initial step of conducting research in an Indigenous way. The community advisory group formed through this relationship will be engaged meaningfully in every research process step.

Conclusion

This tool will be the first to be designed with and for the Indigenous care partners in Canada, which will promote a culturally safe assessment environment for diagnosis of dementia.
Not just cognitive impairment: Using motion‐based technology to examine mobility, balance, and cognition in dementia and MCI
Authors: Dove Erica , Zabjek Karl , Wang Rosalie , Astell Arlene J
Published: February 2022

Background

Dementia and Mild Cognitive Impairment (MCI) are both characterized by impaired cognition, with dementia a more significant impairment that interferes with functioning in daily life. Both groups are also at high risk of falls and reduced physical activity. Yet, little is known about the characterization of this population with regards to balance, mobility, and their relationship to cognition.

Method

Participants with dementia and MCI (n=28; 53.6% female) were recruited from four community‐based adult day programs and invited to participate in a 10‐week motion‐based technology intervention (i.e., Xbox Kinect bowling) to see whether the intervention impacted their balance, movement confidence, and cognition. As part of the data collection procedures, participants completed a demographic survey, as well as the Montreal Cognitive Assessment (MoCA), and the Mini Balance Evaluation Systems Test (Mini‐BEST) at the start of the study. These baseline data were analyzed using descriptive statistics.

Result

In addition to confirming participants’ cognitive impairment (mean MoCA: 12.86/30; range: 2‐25), participants reported a high instance of mobility impairment (16/28 = 57.1%), with many participants using either walkers (12/16 = 75.0%) or canes (4/16 = 25.0%). The entire sample demonstrated significant balance impairments according to the Mini‐BEST (mean: 14.58/28 [<19‐point cut‐off]; range: 6‐21), but only one of 28 participants (3.6%) reported ever receiving treatment (e.g., physiotherapy) for a balance problem.

Conclusion

People with dementia and MCI have a high prevalence of balance and mobility impairments, in addition to their cognitive impairment. Furthermore, there are few instances in which rehabilitation for these physical issues are offered to this population. This may reflect the primary focus on their cognitive impairment but also misconceptions about the capabilities of people with dementia and MCI to engage in rehabilitation. The findings highlight a need for more physical rehabilitation and/or exercise programs for people with dementia and MCI that target balance and mobility, in addition in taking participants’ cognitive impairment into account.
APOE ε4 as a predictor of tauopathies independent of β‐amyloid
Authors: Thompson Kayla I. , Nunez Christina A. , Golden Charles , Stripling Ashley M.
Published: February 2022

Background

Due to the failure of clinical trials that target amyloid β and findings that suggest tau’s role in Alzheimer’s Disease (AD) atrophy and cognitive decline, the investigation of tau‐pathology in AD is needed. While studies have investigated the effect of APOE ε4 on tau‐pathology in mouse models, few have examined the relationship in humans, as well as tau’s role on cognitive decline as a mechanism independent of amyloid β deposition. The aim will be to examine the roles of tau in AD, as an independent pathway.

Method

Utilizing the National Alzheimer’s Coordinating Center (NACC) database, our sample included those determined with AD, as defined by NACC derived variables. Among participants (n= 5391,Mage= 73, SD=10.5) ε4 carriers accounted for 42%. A separate longitudinal sample (n=108, Mage= 70, SD=9.80) was used to determine cognitive decline as measured by the MoCA.

Result

The ANCOVA showed a significant effect of APOE carrier status on neurofibrillary tangles after controlling for neuritic plaques, F(1,5390) = 5643.617, p<.001, partial η2=.512 and separately, after controlling for Thal amyloid phases, F(1,2632) =4809.032, p<.001, partial η2=.646. The regression model showed covariates including sex, race, ethnicity, age, education, and language did not contribute significantly to the model, F(6,102) =2.051, p<=0.66 and accounted for 10.8% of the variation on MoCA scores. Introducing APOE carrier status explained 16.5% of the variation of MoCA and was significant in change, F(1,101) =6.891, p=.010. While addition of all neuropathies explained 32.9% of the model, F(3,98) =7.979, p<.001, post hoc T‐tests revealed that only neurofibrillary tangles had a significant effect on cognitive decline, demonstrating a negative relationship.

Conclusion

These results indicate that the neuropathological effects of APOE ε4 are demonstrated with or without amyloid β deposition, suggesting that apoE may act through tau‐pathways independently. Additionally, while the relationship between APOE ε4 and neuropathology predicts cognitive decline, NFT is the primary driver of cognitive decline in Alzheimer's Disease, while amyloid β deposition has no significant effect.
Best practices in biomarker performance evaluation: Common tool and standards with neuropredict
Authors: Raamana Pradeep Reddy
Published: February 2022

Background

The need for standards in neuroimaging research has been clearly recognized recently in a number of research areas [1]. However, the recommendations made so far do not sufficiently address the complexities involved in the full PRedictive ANAlysis Workflow (PRANAW). In this presentation, I would like to highlight the need, and present some guidelines, towards standardizing generic predictive analysis, that is increasingly becoming common in many areas of neuroscience research. A key application to the Alzheimer’s community being the performance evaluation of biomarkers.

Method

Incomplete/non‐standard reporting of the PRANAW prevents from engaging in any meaningful comparisons. Moreover, given its complexity, it's easy to make choices for individual steps (such as how one performs cross‐validation) in PRANAW, that may not fit well in the full workflow, or produce less accurate results as a whole (with variations in bias or variance). Lack of standards in PRANAW led to the publication of hundreds of papers without clear insight emerging towards whether there is a reliable biomarker for a particular application, and their relative performances.

Result

I will present some ideas to facilitate standardized and easy predictive analysis: 1) A tool (accessible to all skill levels) to perform predictive analysis that implements the best practices, as well as standardized reports. A preliminary attempt in this direction is neuropredict [2]. 2) A cloud repository to receive various standardized reports (either using the tool above, or user's own). 3) A web portal (for visualization and comparison) which lets users and reviewers compare new methods to those in the database.

Conclusion

I believe the publicly available and openly validated tools/infrastructure is necessary now, and prove to be of great value in the long run. Moreover, this would enable a number of Alzheimer’s researchers without native expertise in machine learning or informatics to apply the best practices in biomarker performance evaluation and report more stable and reproducible results. References: [1] Nichols, Thomas E., et al. "Best practices in data analysis and sharing in neuroimaging using MRI." Nature neuroscience 20.3 (2017): 299‐303. [2] Raamana, Pradeep Reddy, “Easy and standardized predictive analysis with neuropredict”, github.com/raamana
The READyR intervention: Focus group feedback from case managers on the initial development of a remote assessment and dynamic response intervention for dementia‐related care needs
Authors: Miller Lyndsey M , Solomon Diane N , Hiatt Shirin , Wu Chao‐Yi , Harbison Sam , Steele Joel S
Published: February 2022

Background

Previous interventions to improve dementia care planning have relied upon self‐reported needs assessments, which are subject to bias and can be inaccurate, especially as dementia progresses, insight diminishes, caregiver burden increases, and needs change more frequently. The Remote Assessment and Dynamic Response (READyR) Program was created to deliver continuous objective in‐home assessments of dementia‐related care needs through a comprehensive sensor platform. The objective of this study was to refine and validate READyR for use by professional care managers of older adults with early‐stage dementia and their spouses/partners.

Method

Evaluation of the READyR Program by 11 professional care coordinators and case managers for families with dementia (across three semi‐structured focus group interview sessions) was used to explore the utility of READyR for assessing dementia‐related needs. Conventional content analysis was used to iteratively code focus group data and to describe prevalent themes.

Result

Prevalent themes included barriers to (e.g. family relationship strain, chaotic assessments, complex care needs) and facilitators of (e.g. proactive family caregivers, tailored assessments, upholding care values) the optimal process for assessing dementia‐related care needs by professional care managers, as well as advantages (e.g. providing new objective insights into safety, function, and routines) and disadvantages (e.g. bringing up new questions about care) for incorporating the READyR remote monitoring data into a values‐based needs assessment.

Conclusion

Qualitative data supported the utility and validity of the READyR Program. Discussion will focus on the potential of READyR as a dynamically tailored needs assessment to improve preparation for future care, mitigate the stress process of dementia, and improve health and well‐being in the spousal care dyad.
Dementia family caregiving experience among Asian American older adults
Authors: Choi JiWon , Park Van Ta , Vuong Quyen , Cheng Joyce , Mukherjea Arnab , Tsoh Janice Y
Published: February 2022

Background

Asian Americans are almost twice more likely to assume caregiving roles for their family than the general population. More Asian American dementia caregivers (DCGs) find their role highly stressful than African American or Hispanic DCGs. Research exploring the challenges and coping strategies for Asian American DCGs is limited. This qualitative study, entitled the SHARE (Share History, Activity, Resilience, and Experience) Project, was conducted to explore the challenges and coping strategies among Asian American DCGs.

Methods

Focus groups and individual interviews were conducted with 29 Asian Americans in the Bay Area between July‐December 2020. The inclusion criteria were: 1) age ≥ 50 years 2) self‐identified as Chinese, Indian, Korean, or Vietnamese American; and 3) provide ≥ 5 hours of care/week currently or in the past for dementia care recipient. Participants were recruited through local community service agencies, the community advisory board of this study, online networks, and word of mouth. Interviews that were conducted in Cantonese, Korean, and Vietnamese were transcribed and translated in . Ethnically/linguistically matched moderators facilitated eight focus groups (six via zoom video and two via WeChat video; three in English, two in Cantonese, one in Korean, and two in Vietnamese) and two individual interviews via telephone (one in English and one in Vietnamese) using the structured interview guide.

Results

About two thirds were current DCGs. Participants reported care recipient’s behavior‐related challenges (e.g., arguing, forgetfulness, wandering) and dementia‐related challenges (e.g., uncertainty, helplessness, duty for 24/7). Across all focus groups, filial piety, love, or responsibility as a family were the main source of enduring. Participants reported exercise, distraction, positive thinking, and having time alone as coping strategies. Having multigenerational families or a care team approach for care recipients appeared to decrease caregiving burden. Not feeling guilty or shame about one’s limitation and using informal/formal support in a timely manner may also help. Some DCGs also expressed a need for social networking with other DCGs for information and emotional support.

Conclusions

Needs for affordable and/or culturally appropriate formal care services were found. Education and training for DCGs given by former DCGs may be useful to disseminate coping strategies.
Quality of life of Alzheimer’s disease patients during the Covid‐19 pandemic January ‐ December 2020 at the National Brain Center Hospital in Jakarta, Indonesia
Authors: Devicaesaria Asnelia
Published: February 2022

Background

During the Covid‐19 pandemic, new habit adaptations applied. This affects the Alzheimer’s Disease patients quality of life who went to our Memory Clinic from January – December 2020.

Method

This study aims to describe the quality of life of Alzheimer's Disease patients based on 13 questions from the QOL‐AD questionnaire filled by the patient's family. A descriptive cross‐sectional study using QOL‐AD questionnaire google form sent by Whatsapp to 42 Alzheimer's disease patients, which was filled by the patient's family. Data collected in the form of gender, age, latest education level, MMSE score and MOCA‐INA score.

Result

From 42 Alzheimer's Disease patients, 24 patient families (57%) responded to the questionnaire. Obtained 10 male (42%) and 14 female (58%) patients, age range 40‐50 years 1 person (4%), 51‐60 years 4 people (17%), 61‐ 70 years 8 people (33%), 71 ‐ 80 years 8 people (33%) and> 80 years 3 people (13%), education level <6 years 3 people (13%), 6‐9 years 2 people (8 %), 10‐12 years 11 people (46%) and> 12 years 8 people (33%), MMSE scores 0‐16 20 people (83%), 17‐23 4 people (17%) and 24‐30 0 people (0%) and MOCA‐INA scores 0‐17 23 people (96%), 18‐25 0 people (0%) and 26‐30 1 people (4%). Quality of life based on gender, age, education level, MMSE score and MOCA‐INA score, the most poor quality is found in the memory of 19 people (79%), the most fair quality is in the finances of 19 people (79%), the most good quality is in marriage with 13 people (54%) and the most excellent quality is in the marriage of 2 people (9 %).

Conclusion

The quality of life of Alzheimer's Disease patients at National Brain Center Hospital during pandemic Covid‐19 is poor to fair.
Developing biomarkers of TDP‐43‐related splicing dysfunction in frontotemporal dementia
Authors: Seddighi Sahba , Hill Sarah , Brown Anna‐Leigh , Qi Andy , Hawrot James , Coon Steven , Petrucelli Leonard , Fratta Pietro , Ward Michael
Published: February 2022

Background

Frontotemporal dementia (FTD) is a rapidly progressive neurodegenerative disorder characterized by prominent atrophy of the frontal and temporal lobes and marked language and/or behavioral disturbances. Mislocalization of the TAR DNA‐binding protein 43 (TDP‐43) – characterized by both its nuclear loss and its cytosolic accumulation – occurs in up to 50% of FTD cases. Recent evidence from our group and others demonstrates that loss of TDP‐43‐dependent splicing activity occurs in FTD patient brains, is an early disease phenomenon, and contributes directly to neuronal death. Monitoring the products of TDP‐43 related mis‐splicing may, thus, yield promising biomarker candidates of early cellular dysfunction in FTD.

Method

We propose a series of proteogenomic studies in human iPSC neurons, post‐mortem brain, and patient biospecimens to identify and develop protein‐based biomarkers of RNA mis‐splicing in FTD. First, we will identify pathologic RNA splicing changes and protein products of mis‐splicing that occur in the context of TDP‐43 depletion in iPSC‐derived neurons. We will next determine which of these predicted transcripts and de novo proteins occur in post‐mortem human FTD brains, as a crucial first step in biomarker development. Finally, we will develop CSF biomarkers of FTD‐related mis‐splicing through a combination of targeted proteomics and ELISA‐based assays of lead candidate biomarkers.

Result

Using CRISPRi knockdown of TDP‐43 in i3Neurons followed by total RNAseq, we detected cryptic exon formation in STMN2 as well as hundreds of additional transcripts. We developed a proteogenomic informatic pipeline to detect de novo protein products of mis‐spliced transcripts in TDP‐43 deficient i3Neurons, revealing two in‐frame de novo peptides in the MYO18A transcript. Furthermore, we detected 38 of these mis‐spliced transcripts in ALS/FTD post‐mortem cortex, including MYO18A.

Conclusion

These preliminary studies indicate that our i3Neuron CRISPRi pipeline can predict disease‐relevant markers of TDP‐43 mis‐splicing and suggest a proteogenomic workflow for development of novel protein‐based biomarkers of mis‐spliced transcripts.Together, these efforts will yield early biomarkers of TDP‐43 related cellular dysfunction that can act as surrogate measures of disease onset and progression in FTD.