bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of cognitive performance from IQ biomarkers and MR volumetrics in the ATN framework depends on diagnosis
Authors: Whittington Alex , Gunn Roger N. 
Published: February 2022

AbstractBackgroundThe A/T/N classification system has emphasised the importance of considering multi‐channel biomarker readouts in AD research. Further, it is important to establish the relationship of these signals to cognitive performance and their relevance to enable optimum inclusion criteria for clinical trials. The IQ analytics platform provides powerful outcome measures for both Amyloid and Tau PET. In this work, we also consider hippocampal volume and investigate the relationship of these A/T/N biomarkers with cognitive performance at different stages of the disease process.MethodAmyloidIQ, TauIQ and MR Volumetric analytics were performed on cross‐sectional data from 605 subjects (CN=376, MCI=173, Dementia=56) downloaded from ADNI where each subject had [18F]Florbetapir, [18F]Flortaucipir and a T1 MRI scan. AmyloidIQ determines the overall amyloid burden as an Amyloid Load percentage (Figure 1 and 2) whilst the TauIQ algorithm deconstructs the more complex Tau signal into global signal and local signal (Figure 3 and Figure 4). The hippocampal volumes for each subject were derived in SPM. We performed a multiple regression analysis with ADAS‐COG as the outcome variable and Global Tau Load, Local Tau Load, Amyloid Load and Hippocampal Volume as predictors. All possible linear models (including interaction terms) were evaluated on each diagnosis group separately and the optimum model was selected at in each case by choosing the model with the lowest BIC.ResultThe hippocampal volume was a statistically significant variable in the optimum model in all diagnosis groups but the statistically significant IQ analytics outcome measures were dependent on the diagnosis (Table 1); in the CN group the key parameter was Amyloid Load, in the MCI group, interestingly, both Local Tau Load and Amyloid Load were statistically significant, finally in the Dementia subjects only the Global Tau Load was found to be statistically significant. When evaluated on all subjects simultaneously, the optimum model explained 49% of the variance in ADAS‐Cog scores.ConclusionThe IQ analytics biomarkers provide orthogonal information that are related to cognitive function in different ways across the disease spectrum. Our results imply that the novel Local Tau Load outcome measure is an important biomarker for stratifying and following MCI subjects.
Characterizing brain structure among middle‐age and older Hispanics/Latinos in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL‐Investigation of Neurocognitive Aging (SOL‐INCA): Preliminary findings
Authors: Stickel Ariana M. , Tarraf Wassim , Gonzalez Kevin A. , Paredes Alejandra Morlett , Zeng Donglin , Cai Jianwen , Isasi Carmen R. , Kaplan Robert , Lipton Richard B. , Daviglus Martha L. , Testai Fenando D. , Lamar Melissa , Gallo Linda C. , Talavera Gregory A. , Gellman Marc D. , Ramos Alberto R. , Gonzalez Hector M. , DeCarli Charles S. 
Published: February 2022

AbstractBackgroundThe older Hispanic/Latino population in the U.S. is projected to grow faster than any racial/ethnic group in the country. Little is known about brain aging in this population, and we remain poorly equipped to detect and track brain changes in this population. We characterized brain aging in a sample of Hispanics/Latinos from diverse backgrounds and investigated differences by sex.MethodNunweighted=1,389 Hispanics/Latinos (ages 39‐85 years; 66% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent brain magnetic resonance imaging (MRI) as part of the Study of Latinos ‐ Investigation of Neurocognitive Aging MRI (SOL‐INCA MRI) ancillary study. MRI outcomes of interest included global (gray matter, total brain) and regional (lobar cortices, hippocampus) brain volumes, lateral ventricle volume, and total white matter hyperintensity (WMH) volume. All MRI measures were residualized for total cranial volume prior to calculating brain aging trajectories using linear regressions that included sex, height, and Hispanic/Latino background as terms in the model. We also tested for effect modification by sex.ResultMean age was 60.8± 10.3 years. Age was associated with decrements in total (β
total
=‐0.66; p<0.001) and hippocampal volumes (β
hippocampus
=‐0.20; p<0.001) as well as incremental enlargements in lateral ventricle and WMH volumes (β
log_lateralvent
=0.48; p<0.001; β
log_WMH
=0.54; p<0.001). Age was also inversely linked to total brain gray matter as well as all lobar cortical gray matter volumes. Age‐related decrements in total and regional brain volumes, but not lateral ventricle or WMH, were exacerbated in men relative to women (all p<0.05). Adjusting for height and background, women had larger total brain (standardized beta β
total
=0.27; p<0.001), frontal (β
frontal
=0.27; p<0.001), and parietal (β
parietal
=0.17; p=0.025) volumes, smaller hippocampal and lateral ventricle volumes, and larger gray matter volumes, but did not differ in WMH as compared to men.ConclusionThese findings suggest that increasing age is associated with smaller regional MRI brain measures in Hispanic/Latino individuals. Aging patterns in gray matter volumes appeared to be exacerbated among men compared to women whereas age‐related differences in lateral ventricular volume and white matter hyperintensities were consistent between sexes. Our findings help establish the trajectories of brain aging among middle‐aged and older Hispanics/Latinos.
Differential cognitive correlates of tau and neurofilament light chain in cerebrospinal fluid of frontotemporal lobar degeneration patients with and without Alzheimer’s markers
Authors: Vasilevskaya Anna , Taghdiri Foad , Multani Namita , Salvo Cristina , Anor Cassandra Jessica , Misquitta Karen , Burke Charles , Tang‐Wai David F. , Lang Anthony E. , Fox Susan , Slow Elizabeth , Tartaglia Maria Carmela 
Published: February 2022

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) phenotypes can be associated with Alzheimer’s disease (AD). It is unknown whether differences exist in relationship between markers of degeneration such as tau and neurofilament light chain (NFL) and cognition between FTLD with and without AD.Method40 FTLD patients were included in this study: (A) 31 FTLD without AD [5 behavioral variant FTD, 11 corticobasal syndrome (CBS), 1 non‐fluent variant primary progressive aphasia (nfvPPA), 12 progressive supranuclear palsy (PSP), 2 semantic variant PPA (svPPA); age (67.74±10.28); sex (20M:11F)]; and (B) 9 FTLD positive for AD [6 CBS‐AD, 1 nfvPPA‐AD, 1 PSP‐AD, 1 svPPA‐AD; age (66±8.46); sex (5M:4F)]. CSF levels of Aβ42, phosphorylated tau (p‐tau) & total tau (t‐tau) were measured using sandwich ELISA and AD pathology was deemed present if p‐tau > 68 pg/mL and Aβ42 to t‐tau index < 0.8. CSF NFL was measured using SIMOA. Full neuropsychological battery was completed, controlled for age/education.ResultIn the FTLD cohort, significant relationships were observed between CSF t‐tau and CDR sum of boxes (r=0.599, p=.001) and MOCA (r=‐0.530, p=.004). In FTLD group, digit span backwards (DSB) was significantly associated with CSF t‐tau (r=‐0.492, p=.009) & NFL (r=‐0.427, p=.02); while verbal fluency, Trail Making Test part A & digit span forward (DSF) were only related to NFL (r=‐0.410, p=.03; r=0.463, p=.02; r=‐0.374, p=.05, respectively). In the FTLD‐AD cohort, MOCA was significantly associated with CSF p‐tau (r=‐1.00, p<.0001) & t‐tau (r=‐0.887, p=.02); memory and executive function tests including California verbal learning test 30s recall, DSB & DSF were significantly associated with CSF t‐tau (r=‐0.788, p=.04; r=‐0.836, p=.04; r=‐0.760, p=.07, respectively); while verbal fluency & category fluency were significantly associated with CSF markers of NFL (r=‐0.841, p=.04; r=‐1.00, p<.0001), p‐tau (r=‐0.981, p<.001; r=‐1.00, p<.0001), & t‐tau (r=‐0.984, p<.001; r=‐0.977, p=.004).ConclusionIn both FTLD with and without AD, overall severity was related to CSF t‐tau but executive function in FTLD without AD was related to CSF NFL while in FTLD‐AD it was related to p‐tau and t‐tau. The presence of AD in FTLD phenotypes alters relationship to NFL, which may be indicative of differences in extent of degeneration.
PS1 mutation position influences regional PiB‐uptake and white matter lesion volume
Authors: Joseph‐Mathurin Nelly , Feldman Rebecca L. , Toomer Carmen , McKay Nicole S. , Strain Jeremy F. , Kilgore Collin B. , Gordon Brian A. , McCullough Austin A. , Chen Charles D. , Schultz Stephanie A. , Cruchaga Carlos , Xiong Chengjie , Morris John C. , Bateman Randall J. , Chhatwal Jasmeer P. , Benzinger Tammie L.S. ,   Dominantly Inherited Alzheimer Network
Published: February 2022

AbstractBackgroundMutations in the Presenilin‐1 (PS1) gene account for 80% of dominantly inherited Alzheimer disease (DIAD). Previous findings suggest PS1 mutation position relative to codon 200 may impact the distribution and amount of cerebral β‐amyloid pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of mutation position on imaging markers of β‐amyloidosis and small vessel disease with a focus on regional variability and disease progression.MethodIndividuals with PS1 mutations before (Pre‐200MC, n=76) or after codon‐200 (Post‐200MC, n=126) and non‐carriers of these mutations (n=129) from the same families were assessed with the Clinical Dementia Rating (CDR) scale and underwent neuroimaging including PiB‐PET to assess β‐amyloid burden and T2‐FLAIR MRI to assess white matter lesions. A subset (52 non‐carriers, 63 Pre‐200MC, 73 Post‐200MC) had longitudinal data available. Accounting for estimated year to symptom onset (EYO) and APOE‐ɛ4 status, cross‐sectional and longitudinal linear mixed‐effects models evaluated the effect of mutation positions on PiB‐uptake (SUVR) in 40 FreeSurfer regions, white matter hyperintensity (WMH) volumes in periventricular and deep areas, and their associations with dementia.ResultPre‐200MC had earlier age of symptom onset versus Post‐200MC (43.34±8.97 versus 46.81±7.55 years, p<0.0001). Pre‐200MC presented with higher amyloid burden (mean cortical SUVR of 2.28±1.27 versus 1.91±1.0, p<0.02). Differences were observed mostly in frontal, temporal, and subcortical regions. Stronger associations between PiB‐uptake and EYO were observed in Pre‐200MC versus Post‐200MC in nearly all regions (precuneus: F(1,192)=9.37, p<0.01; caudate: F(1,192)=17.65, p<0.001; Figure 1A). In contrast, Post‐200MC presented with stronger associations of periventricular WMH with EYO (F(1,25)=5.02, p<0.05) and deep WMH with dementia as measured by CDR‐SB (F(1,25)=14.01, p=0.01). Longitudinal analyses showed higher rates of change in PiB uptake in Pre‐200MC versus Post‐200MC in several frontal, temporal, and striatal regions (inferior temporal: F(1,171)=13.71, p<0.0005; caudate: F(1,171)=8.22, p<0.005; Figure 1B). Mutation position did not influence rates of change in WMH volumes nor cognitive decline.ConclusionThese findings confirm that mutation position within the PS1 gene influences disease presentation in DIAD. Improved characterization of heterogeneity in disease progression may inform further clinical trials in this population. Further investigation into biological mechanisms responsible for these differences is necessary. Funding: AARFD‐20‐681815;U19AG032438.
Piloting of a compensatory memory digital health intervention in a group of individuals with subject cognitive complaints
Authors: Weakley Alyssa , Schmitter‐Edgecombe Maureen , Namboodiri Sudev , Randhawa Jagnoor , Farias Sarah Tomaszewski 
Published: February 2022

AbstractBackgroundTraditional paper‐based calendars and to‐do lists have limitations related to difficulty retrieving information and no automated way to prompt completion of activities. Such limitations may be overcome using a digital format through organized files, search functions, and alarms. This pilot project trained older adults at risk for cognitive decline to use the Digital Memory Notebook (DMN), a tablet‐based application, to support everyday memory. The primary goal was to obtain preliminary information regarding a 6‐week, group‐based DMN training intervention in terms of acceptability and satisfaction.MethodTen participants with subject cognitive complaints (SCC), a risk factor for Alzheimer’s disease, enrolled in the study. Participants met 2‐hours per week for 6‐weeks. A manualized curriculum covered specific DMN functions and weekly homework/goal‐setting targets. Following the intervention, participants continued to use the DMN for 4‐weeks and then provided feedback, which was audio recorded and transcribed.ResultsThree participants left the study after the initial consenting session and one participant discontinued after the second session, all specifying that they were already efficiently using similar electronic systems. The remaining six participants had an average attendance rate of 89%, which was above our initial target rate of 80%. Overall, participants reported that they enjoyed the group intervention and believe the DMN is a useful everyday memory aid. Participants endorsed seeing benefit of having multiple functions (e.g., calendar, to‐do list, notes, journal) in a single, senior‐friendly application. Participants particularly enjoyed the journal and note taking functions, emphasizing the organization and search functions to be the most beneficial. Three participants chose to download the DMN onto their personal tablet device for continued use and one participant downloaded a notes/journal specific application to their phone.ConclusionsInitial feedback for the DMN group intervention is promising and suggests that individuals find value in using the DMN as a compensatory tool. That said, participants may lack initial buy‐in if they are already using a similar electronic system. Information gleaned from this pilot study will help improve the group intervention and digital health tool.
Dementia grief reconceptualized: Systemic review of psychotherapeutic approaches for BPSD and NPS during COVID‐19
Authors: Ione Adrienne 
Published: February 2022

AbstractBackgroundThe biopsychosocial effects of COVID‐19 experienced by people ages 65 and greater are unprecedented. The gravity of losses will not be realized for decades. Physical, personal, economic and social constraints remain in place, generating feelings of stress and anger. Even graver of a situation is a subset of this population ‐ people who have been diagnosed with dementia and those who are more vulnerable to stress effects on the aging brain ‐ where mental health ramifications of stress are magnified. Traumatic experiences hold the possibility of reactivating previous losses that have not been fully integrated into the gut‐brain axis. At the same time, traumatic events present possibilities in releasing emancipating power when losses are modulated by access to grief‐based psychotherapies. With access to psychotherapy remaining severely limited for the most vulnerable among us, the vastness of mental health disparities remains undocumented.MethodsCritically review psychological intervention studies investigating the biopsychosocial effects of COVID‐19 among people with dementia and assess the evidence for incorporation of grief‐based psychotherapy and presence of strengths‐based language. A systematic review of Web of Science databases was carried out by using keywords dementia and COVID‐19, employing Boolean operating word AND, with search results limited to 2020‐2021.ResultsFrom a total of 229 initial search results, 156 did not meet study criteria and were omitted. Of the 73 studies that met criteria, six thematic therapeutic approaches emerged: neuroscience, management of BPSD, pharmacological, lifestyle, social work, and technological interventions. Secondarily, studies were assigned to one of three categories on viewing COVID‐19 as an event that is: limiting or constraining, growth opportunity, or something else.ConclusionCurrent evidence suggests that the biopsychosocial effects of COVID‐19 and dementia present a complex, dynamic and evolving relationship. Prolonged and sustained exposure to stress and trauma develops a deepening cognitive divide, where people transition from mild cognitive impairment to meeting diagnostic criteria of dementia. These times demand increasing access to grief‐informed psychological services, such as Active Capabilities Therapy, in an attempt to diminish the gut‐brain axis harms of BPSD and NPS as experienced by the individual.
Exploring the basis of phenotypic diversity in Alzheimer’s disease
Authors: Wan Yutong 
Published: February 2022

AbstractBackgroundAlzheimer’s Disease (AD) is the most common type of dementia and affects more than 50 million people around the world. Although there is no effective treatment for the disease at the moment, early detection is still critical to start an early management plan and try out various interventions. Besides the stereotypical Amnestic Syndrome, many atypical pehnotypes exist which make accurate early diagnosis challenging.MethodExamined Corticobasal Syndrome (CBS), behavioural variant of Frontotemporal Dementia (bvFTD), Posterior Cortical Atrophy (PCA), and Primary Progressive Aphasia (PPA) cases correlating with AD's onset. As such, this literature review investigated the reasons underpinning the selective regional vulnerability leading to clinical diversity in AD.ResultThe majority of AD is sporadic, caused by phosphorylated‐tau aggregates and amyloid‐β depositions in neurons or extracellular space. Increasing age is the dominant risk factor for AD development and the major genetic risk factor for sporadic AD is ApoE4. A small proportion of AD is familial, due to mutations in APP, PSEN1, and PSEN2 genes. The available research findings suggest that diverse clinical presentations correlated with selective degeneration and pathology development in different brain regions. The different regions with originally pathological alternations of each phenotype may help explain the conundrum of polytropic presentations, that primary motor cortex is significantly affected in CBS, basal ganglia in bvFTD, posterior part of the brain in PCA, and temporoparietal areas in PPA. Research indicates that the presence of ApoE4 is significant for the development of all AD phenotypes. In addition, while some studies reported several famial cases, these are not typically thought to be representative and thus more studies are needed.ConclusionThe diverse clinical phenotypes of AD, including AS, CBS, bvFTD, PCA, and PPA, share similar pathogenesis and genetic factors, but each phenotype has divergent patterns of regional distribution of the pathology.
Effects of the culturally sensitive DEmentia Competence Education for Nursing home Taskforce (DECENT) programme in mainland China: A quasi‐experimental study
Authors: Zhao Yayi , DING Yaping , Liu Li , Chan Helen YL 
Published: February 2022

AbstractBackgroundA number of dementia care educational programmes are developed to build nursing‐home staff’s care competence in the Western culture. However, their applicability and cultural relevancy to Chinese population are questionable. This study aimed to develop and evaluate a Culturally Specific DEmentia Competence Education for Nursing home Taskforce (DECENT) programme in mainland China.MethodA multi‐centre two‐arm repeated‐measures quasi‐experimental study was conducted with 217 care staff from 10 nursing homes. Nursing homes were pair‐matched and allocated into intervention (n = 5) and control group (n = 5). Participants were allocated into intervention group (n=101) who received the DECENT programme or control group (n = 116) who received the printed educational materials according to the settings they worked. The DECENT programme comprised eight topics and was delivered through multiple pedagogical strategies by a qualified educator once per week for 60‐90 minutes over eight weeks. The study outcomes were the sense of competence in dementia care, dementia knowledge, attitudes towards people with dementia, person‐centred care in nursing homes and the severity of behavioural and psychological symptoms of dementia (BPSD) of residents with dementia and staff‐perceived disturbance. They were measured at baseline (T0), immediately post‐intervention (T1) and 3‐month after intervention (T2). Generalised estimating equation models were performed to analyse the effect.ResultThe intervention group improved more significantly than the control group in sense of competence in dementia care both at T1 (B = 5.24, p < .001) and T2 (B = 4.43, p = .013). In terms of dementia knowledge and person‐centred care in nursing homes, the intervention group only showed significant improvement at T1 (B = 3.18, p = .001; B = 5.75, p = .018, respectively), but not at T2 (p = .089 and .104, respectively), when compared to control group. Attitudes towards people with dementia and severity of BPSD and staff‐perceived disturbance were not significant both at T1 and T2 relative to control group.ConclusionThe DECENT programme is effective in improving nursing‐home staff’s perceived dementia‐care competence. Nevertheless, continual learning and support at organisational level is needed for cultivating changes in practice and residents’ outcomes.
Insights on FTD: An externally led patient‐focused drug development meeting
Authors: Niehoff Debra , Dodge Shana G , Graham Elizabeth , Barker Megan S , Cosentino Stephanie , Wheaton Dianna KH , Denny Sharon S , Dacks Penny A , Dickinson Susan 
Published: February 2022

AbstractBackgroundUnderstanding the lived experience of those affected by a disorder should be central to the development and evaluation of therapeutics. Disease‐specific Externally Led Patient‐Focused Drug Development (EL‐PFDD) meetings were established by the FDA to hear directly from those living with a condition about experiences, symptoms, treatments, and hopes for new therapies. Such insights are particularly important for frontotemporal degeneration (FTD), a genetically and clinically heterogenous condition that includes behavioral variant FTD (bvFTD), primary progressive aphasias, progressive supranuclear palsy, corticobasal syndrome, and ALS with FTD.MethodOn March 5, 2021, AFTD hosted an EL‐PFDD for FTD; 382 caregivers, family members, and persons with FTD participated, plus 171 professionals. In preparation, AFTD and the FTD Disorders Registry conducted the FTD Insights Survey, gathering information on clinical and genetic characteristics of respondents; the earliest, current, and most concerning symptoms; and perspectives on treatments and clinical trials. 1,237 persons with FTD, care partners/caregivers, and family members in the US, Canada and UK had completed the survey by October 31, 2020.ResultPeople living with all FTD syndromes described challenges in activities of daily life, including preparing meals, managing finances, driving, and conversing. Symptoms vary within and across disorders, encompassing language, motor function, thinking/decision‐making, interpersonal/emotional functioning, among others. Many people diagnosed have limited awareness of their symptoms (65% bvFTD; 37% other FTD disorders). In genetic FTD, the path to diagnosis can be simpler, yet a lifetime of perceived or known risk can dramatically influence life decisions. The lack of effective, approved therapies – disease‐modifying or symptomatic – was a universal concern. Non‐prescription and off‐label prescription therapies may stabilize symptoms temporarily while prescribed acetylcholinesterase inhibitors can exacerbate symptoms. Many people are willing to participate in clinical research depending on illness stage and burden imposed by trial design.ConclusionThe community of those affected by FTD offers insights into this condition as partners in research. Central themes of the EL‐PFDD meeting for FTD will be summarized by AFTD in a Voice of the Patient reported submitted to the FDA. Results of the FTD Insights Survey are available to researchers through the FTD Disorders Registry.