bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross vendor test‐retest validation of diffusion tensor analysis along the perivascular space (DTI‐ALPS) method for evaluating glymphatic system function in vascular cognitive impairment and dementia (VCID)
Authors: Liu Xiaodan , Barisano Giuseppe , Shao Xingfeng , Jann Kay , Ringman John M , Lu Hanzhang , Arfanakis Konstantinos , Arvind Caprihan , Decarli Charles , Gold Brian T. , Maillard Pauline , Satizabal Clandia L. , Fadaee Elyas , Habes Mohamad , Stables Lara , Singh Herpreet , Fischl Bruce , van der Kouwe Andre J. , Schwab Kristin , Helmer Karl G. , Greenberg Steven M. , Wang Danny J.J.
Published: December 2023

Background

Glymphatic system (GS) is a recently discovered brain‐wide perivascular fluid transport system in the cerebral nervous system (CNS)(Benveniste H et al., 2019) The impairment of glymphatic transport has been demonstrated to be associated with several neurological diseases, in particular the vascular cognitive impairment and dementia (VCID)(Tang J et al., 2022). The diffusion tensor analysis along the perivascular space (DTI‐ALPS) was proposed to non‐invasively evaluate the GS clearance dysfunction which has been used to investigate the GS in various pathologies(Taoka T et al., 2017, Hsu JL et al., 2022). However, studies on the cross‐vendor and test‐retest reliability of DTI‐ALPS method are lacking. The current study aimed to perform cross‐vendor, inter‐rater and test‐retest validations of DTI‐ALPS method by using a cohort from the MarkVCID consortium.

Method

Fifty participants’ DTI data from the MarkVCID consortium (consists of 7 sites) were included in this study: 15 participants were scanned on four MRI scanners; 35 participants underwent two MR scans within 14 days. The DTI data were acquired used a single shell, b = 1000s/mm2, 40‐direction with a voxel size of 2.02.02.0mm3 and six b = 0 s/mm2 on 3T MR scanners from seven sites, including two Siemens systems, one Philips system and one GE system. Two pipelines by using DSI studio and FSL software were developed for data processing and ALPS index calculation (Figure 1). The mean ALPS (mALPS) index was obtained by the average of bilateral ALPS index and was used for testing the inter‐rater, cross‐vendor and test‐retest reliability. The association between mALPS index and Montreal Cognitive assessment (MoCA) scores were evaluated using a general linear model with age and gender as covariate.

Result

The Bland‐Altman plot and scatterplot illustrated the validation results of the mALPS index analyzed using DSI studio and FSL pipelines (Figure 2). The mALPS index demonstrated favorable inter‐scanner reproducibility (ICC = 0.77 to 0.95, P< 0.001), inter‐rater reliability (ICC = 0.96 to 1, P< 0.001) and test‐retest repeatability (ICC = 0.89 to 0.95, P< 0.001). A significantly positive correlation was observed between mALPS index and MoCA scores (r = 0.502, P< 0.01) (Figure 3).

Conclusion

The mALPS index offers a robust potential biomarker for evaluating GS clearance function in VCID.
The use of Event Related Potentials to predict amyloid PET status among patients from a memory disorders clinic
Authors: Chadalavada Myna , Marin Anna , Schiloski Kylie A , Suh Cheongmin , Uppal Prayerna , Palumbo Rocco , Budson Andrew E , Turk Katherine W
Published: December 2023

Background

Amyloid PET scans provide in vivo evidence of Alzheimer’s Disease (AD) however, due to high cost and limited insurance coverage, they are not available as part of standard clinical care. Event Related Potentials (ERPs) are inexpensive, and non‐invasive method to directly measure brain physiology that may allow an alternative method for detection of AD pathology.

Method

We investigated whether ERPs together with neuropsychological data are predictors of amyloid PET status in patients with memory complaints. Older veterans aged 50‐100 were recruited from a memory disorders clinic at VA Boston Healthcare System. Participants underwent a standard neuropsychological battery and an ERP auditory oddball protocol. Twenty‐eight patients had a positive amyloid PET scan, and thirty‐nine patients had a negative amyloid PET scan.

Results

Two neuropsychological measures (CERAD Delayed Recall and MMSE) were predictors of amyloid PET status. Increased P200 target amplitude (Figure 1B), and decreased P200 standard latency (Figure 1A) in patients with amyloid PET positive scan were found. ERP‐P200 amplitude in response to target tones and ERP‐P200 latency in response to standard tones were also predictors of amyloid PET status. The highest classification accuracy was obtained when combining CERAD Delayed Recall, MMSE and ERP‐P200 standard latency.

Conclusion

ERP‐P200, especially when combined with cognitive measures of delayed memory and overall cognitive function, was predictive of amyloid beta (Aβ) load in the brain of patients from a memory disorder clinic. Increased P200 amplitude, and decreased P200 latency in patients with amyloid PET positive scan might suggest hyperactivation of perceptual bottom‐up processes to compensate for AD‐related synaptic loss in the fronto‐parietal networks.
Recalibrating narratives of gender differences in ADRD research: Lessons and opportunities from the Global South
Authors: Esiaka Darlingtina
Published: December 2023

Sex and gender differences in brain health and cognitive decline are increasingly visible as we grapple with the profound impact of Alzheimer’s disease and related dementia (ADRD). However, the conventional narratives of sex and gender differences in ADRD research are often grounded in mainstream Global North cultural values. Despite its manifestation, the indigenous and non‐western concepts of sex and gender and the intersecting narratives of social vulnerability remain largely unexplored. Accurate characterization of sex and gender differences in ADRD must include narratives evident in high‐incidence populations or regions beyond the Global North. A full account of sex and gender differences in ADRD requires changing the narrative to interweave critical approaches. Specifically, it requires that we systematically examine how to reframe, repair, or otherwise change narratives about sex and gender differences in AD/ADRD research that do not reflect the experiences of people in the Global South. The talk will serve as a resource and a call to action regarding how one can produce and critically consume knowledge that affirms and represents all experiences ‐ including indigenous people and people in the Global South. Further, it will foster innovative approaches to empirical research on sex and gender differences in AD/ADRD and help us understand current research findings in the field and their limited capacity to inform research and clinical practice outside of the Global North.
Can Plasma Optical Density or Transmission be used for helping AD Diagnosis?
Authors: Li Wei , Arnold Elizabeth , Jenkins Bradley , Hemby Leslie , Patel Hailey , Vobbilisetty Nandini , Li Daniel , Mamaeva Olga , Maqbool Muhammad
Published: December 2023

Background

Currently, diagnosis of Alzheimer’s disease (AD) mainly relies on clinical and neuropsychological tests, which are not only costly but also time‐consuming and burdensome to the patients. The only way to confirm an AD diagnosis is the post‐mortem detection of amyloid plaques and neurofibrillary tangles. The research on biomarkers has some significant progresses in recent years but none is available to be used clinically that can meet the sensitivity and specificity requirements.

Method

Blood samples were collected from participants with different diagnoses: early‐onset AD, late‐onset AD, and those without an AD diagnosis (controls). 22 participants had early‐onset AD, 72 participants had late‐onset AD, and 48 participants were in the control group. The optical density (OD), as well as transmission, were measured from blood plasma samples using a densitometer. An analysis of variance (ANOVA) was performed using the diagnosis group as the independent variable with post hoc Bonferroni correction.

Result

The optical density for the late‐onset AD group was 0.356 ± 0.009, which is significantly higher than the counterpart measure for the control group of 0.313 ± 0.012 (p = 0.015). By contrast, the optical density for the early‐onset AD group was 0.361 ± 0.017, which is not significantly different from the late‐onset group (p = 1) or the control group (p = 0.065). As expected, the late‐onset AD group had an average transmission of 0.947 ± 0.002, which is at the level compared with the early‐onset AD group of 0.947 ± 0.004 (p = 1) but significantly lower than the same measure from the control group of 0.958 ± 0.003 (p = 0.006).

Conclusion

The physical properties of blood plasma: OD or transmission can help with an AD diagnosis, which is particularly useful for diagnosing late‐onset AD.
Initial experiences with amyloid‐related imaging abnormalities in patients receiving aducanumab following accelerated approval
Authors: Howe Matthew D. , Britton Karysa J. , Joyce Hannah E , Faust Melanie A. , Dawson Brittany C. , Riddle Meghan C. , Salloway Stephen
Published: December 2023

Background

Aducanumab is the first approved amyloid‐lowering immunotherapy for Alzheimer’s disease (AD). There is little real‐world data to guide the management of amyloid‐related imaging abnormality (ARIA), a potentially serious side‐effect requiring surveillance with serial magnetic resonance imaging (MRI). The current study seeks to characterize the symptoms, clinical course and management of ARIA in memory clinic patients treated with aducanumab.

Method

We conducted a non‐blinded, observational case series of patients who received aducanumab from June 16, 2021 to August 1, 2022 at the Butler Hospital Memory and Aging Program. Inclusion: (1) Clinical diagnosis of mild cognitive impairment (MCI) or mild dementia due to AD, (2) confirmed amyloid positivity (PET/CSF), and (3) Mini Mental State Exam (MMSE) = 20‐30. Exclusions: (1) MRI with > 4 microhemorrhages, > 1 area of superficial siderosis or significant cerebrovascular disease, (2) MRI contraindication, (3) anticoagulation and (4) unstable medical/psychiatric conditions. Participants received monthly aducanumab infusions, titrated to a dose of 10 mg/kg, with ApoE genotyping and enhanced MRI monitoring adapted from the phase 3 trials. The primary outcome of the study was the identification of ARIA‐E by MRI. Secondary outcomes included severity of ARIA, clinical course, and time to resolution.

Result

Out of 24 patients treated with aducanumab, we identified ARIA‐E in 6 patients (25%), all ApoE‐ε4 carriers, and 4 of whom had moderate‐severe radiographic severity. Comorbid ARIA‐H occurred in 3 patients, 1 of whom also had new onset of cerebellar metastatic cancer. Symptomatic ARIA occurred in 3 patients and included headache, confusion, gait instability, and word‐finding difficulties. Treatment was discontinued in 4 cases of moderate‐severe ARIA‐E, temporarily held in 1 moderate/asymptomatic case, and dosed through in 1 mild/asymptomatic case. All cases of ARIA‐E resolved without hospitalization or corticosteroids (mean duration = 3 months, range, 1 ‐ 6 months).

Conclusion

Additional amyloid‐lowering antibodies, associated with ARIA, may soon become clinically available. These data support the careful patient selection, ApoE genotyping, MRI surveillance and individualized dosing recommended in the updated FDA prescribing information and Appropriate Use Recommendations.
Synthetic FDG‐PET hypometabolism sensitivity validation in AD
Authors: Collin‐Castonguay Pénéloppe , Gourdeau Daniel , Potvin Olivier , Duchesne Simon
Published: December 2023

Background

The availability of 18‐F fluorodeoxyglucose positron emission tomography (FDG‐PET) is not universal. We hypothesized that synthetically generated FDG‐PET images would be as sensitive to detecting the pattern of hypometabolism associated with AD as real images.

Method

We developed a deep learning‐based method to produce synthetic FDG‐PET images from 1,828 T1‐weighted MRI / real FDG‐PET image pairs from the ADNI dataset, and validated the technique on a further 284 image pairs. The technique generated synthetic FDG‐PET images which were then processed to compare Standardized Uptake Value Ratio (SUVR) with the pons as reference in 81 brain regions as defined in the Desikan‐Killiany‐Tourville and subcortical default FreeSurfer atlases.

Result

We tested the differences between synthetic and real FDG‐PET on 745 image pairs (205 controls, 365 mild cognitive impairment (MCI) and 175 AD)(Table 1). Correlations in SUVR values between synthetic and real FDG‐PET ranged between weak (r = 0.13) to strong (r = 0.63), with moderate results in key regions for AD (bilateral precuneus, r = 0.43; bilateral posterior cingulate, r = 0.37). There were significant between‐group (control vs MCI and control vs AD) differences in SUVR values for all regions between synthetic and real PET‐FDG (Figure 1) with synthetic FDG‐PET having lower values. Inter‐group effect sizes were not significantly different in the majority of brain regions (76/81)(Figure 2), with similar effect sizes in the right precuneus (synthetic: ‐0.98 vs original: ‐1.37), left (‐0.77 vs ‐1.0459) and right (‐0.80 vs ‐1.04) posterior cingulate, but different for the left precuneus (‐0.91 vs ‐1.33).

Conclusion

Synthetic images would increase patients’ accessibility to a meaningful modality for disease assessment while decreasing their exposure to radiation and resources in the health care system.
Assessing bidirectional longitudinal associations between changes in social network structures and cognitive decline in late life
Authors: Zhang Yun , Clouston Sean A.P. , Hou Wei , Scott Stacey B , Smith Dylan
Published: December 2023

Background

The role of social networks in maintaining cognitive health is unclear, in part because few longitudinal studies have explored bidirectional associations between changes in social network structures and cognition.

Method

Secondary analyses of data collected during nine waves of the National Health and Aging Trends Study (NHATS; 2011‐2019) were conducted. Global cognition was the main outcome, but domain‐specific analyses examined episodic memory, orientation, and executive function. Linear mixed models were used to investigate longitudinal effects of neighborhood social cohesion and physical environment on cognitive decline. Dual‐outcomes models were used to examine bidirectional associations between social network structures and cognitive decline. Covariates included socioeconomic status, physical measurements, mental health, and lifestyle indicators.

Result

Eligible participants (N = 7,325) were recruited at baseline and followed for an average of 4.86±3.22 years. Bivariate correlations indicated that slopes of changes in social networks or participation and cognitive decline were positively correlated. Having more friend ties and a higher percentage of college graduates at baseline were associated with slower declines in global cognition and episodic memory, whereas higher global cognition at baseline was associated with smaller changes in social network size. Less disorientation at baseline was associated with a slower decline in social participation.

Conclusion

Findings indicate bidirectional longitudinal relationships between social network structure and cognitive decline. Social networks may improve cognitive health but are also vulnerable to cognitive decline related to disorientation.
Vitamin B12 deficiency and cognitive impairment: Is there a distinctive cognitive domain affected? A descriptive study in Buenos Aires
Authors: Boccazzi Julian Fernandez , Rojas Galeno , Guillen Jonathan Cubas , Gatto Emilia , Persi Gabriel Gustavo , Hierro Xavier Merchan , Aldinio Victoria , Seguí Josefina , Camino Victoria , Muniagurria Santiago , Gilbert Afra , de Silva Nahuel Pereira , Eizaguirre Barbara
Published: December 2023

Background

Vitamin B12 deficiency is associated with cognitive‐behavioral disorders, which may be potentially reversible. No specific associated cognitive domain has been established and alterations in episodic memory, verbal fluency, attention and executive functions, praxia and visuoconstruction have been described. The objective of this work is to evaluate and describe the cognitive domains affected in patients with cognitive impairment associated with vitamin B12 deficiency.

Method

Cross‐sectional observational study conducted at the Trinidad Mitre sanatorium of Buenos Aires City. Patients with cognitive impairment and vitamin B12 deficiency were analyzed. Information was collected on the cognitive domain affected (taking as altered value the Z score ≤‐1.5 according to age and educational level, obtained in the neurocognitive evaluations), cognitive profile, magnetic resonance imaging features and mean consultation‐supplementation time.

Result

25 patients with vitamin B12 deficiency and cognitive complaint were analyzed, with a mean age of 68.5 years. 83% presented multidomain mild cognitive impairment being 60% with subcortical pattern. Memory and attention were the most affected domains in 80% of the sample, followed by executive functions with 52%. The most deficient tests were the direct digit test (68%), serial memory (56%), deferred logical memory (52%) and Trail Making B (52%). Nearly 52% presented mild depressive symptomatology. A 56% of the sample presented with severe B12 deficiency with 32% elevation of plasma homocysteine. Supplementation was performed intramuscularly in 68% of the patients with a mean symptomatology‐supplementation onset time of 10.8 months. 92% of the patients presented subjective improvement after supplementation, 32% had control global test evaluation with improvement in all of them and 50% of this group presented control cognitive evaluation with improvement in previously deficient domains.

Conclusion

According to our findings we conclude that these patients with vitamin B12 deficiency present a multidomain pattern with special affectation of memory, attention and executive functions; of mild degree and potentially reversible. The reversibility of the picture could be related to high doses of B12 and early supplementation, using control cognitive assessments as an objective measure of improvement.

References

Reynolds E. Lancet Neurol. 2006 Nov;5(11):949‐60. Eastley R. Int J Geriatr Psychiatry. 2000 Mar;15(3):226‐33. Robins Wahlin. Biol Psychol. 2001 Jun;56(3):247‐65.
Naturalistic Assessment of Reaction Time Variability in Older Adults at Risk for Alzheimer’s Disease
Authors: Welhaf Matthew S. , Wilks Hannah M , Aschenbrenner Andrew J. , Schindler Suzanne E. , Benzinger Tammie L.S. , Gordon Brian A. , Cruchaga Carlos , Morris John C , Hassenstab Jason J.
Published: December 2023

Background

Breakdowns in attentional control may underscore cognitive changes seen in the earliest stages of Alzheimer’s disease (AD). One way to measure these changes is to assess variability in cognitive performance. Variability in cognition may be most evident when repeatedly sampled over hours or days and in different environmental contexts or at different times of day. We analyzed data from an ongoing smartphone‐based study of cognition in AD which utilizes extremely brief cognitive tests taken remotely over several days in natural environments.

Method

Older adults (N = 319, aged 75 +/‐ 5 years) completed repeated cognitive testing on the Ambulatory Research in Cognition (ARC) platform and had CSF or PET amyloid biomarkers and APOE genotype available. RTSD was assessed in a brief processing speed task by taking the SD of correct RTs. All models adjusted for baseline age, education, and gender.

Result

Averaging across sessions, symptomatic participants (indicated by Clinical Dementia Rating® (CDR®) > 0) showed more variability than asymptomatic (CDR 0) participants (p = 0.009). APOE ε4 carriers showed more variability than non‐carriers, although this was not significant (p = 0.067). More fine‐grained models considered RTSD within each session (e.g. from trial‐to‐trial) using mixed effects models. Symptomatic participants exhibited greater trial‐to‐trial RTSD compared to asymptomatic participants (p = 0.001). APOE ε4 carriers also exhibited greater trial‐to‐trial RTSD compared to non‐carriers (p = 0.004). When limiting the sample to asymptomatic participants to determine if there were changes in the preclinical stage of AD, there remained a strong APOE ε4 effect, with carriers exhibiting greater trial‐to‐trial RTSD than non‐carriers (p = 0.005). Interestingly, amyloid was not significant in any models.

Conclusion

Older adults at risk for AD show increased RTSD even in brief assessments. These subtle fluctuations in attention were most evident in APOE e4 carriers at very short time intervals, and less so when averaged across trials and sessions. Overall, these findings suggest that fluctuations in attention in preclinical AD are most evident from moment to moment, highlighting the need for fine‐grained and repeated assessment of attentional control.
Identification of genetic regions associated with Alzheimer ‘s disease blood‐based biomarkers in Mexican American families
Authors: Almeida Marcio A
Published: December 2023

Background

Dementias are heterogeneous age‐associated neurodegenerative disorders generally included in the broad term, Alzheimer’s disease (AD) and related dementias (ADRD). ADRD affects individuals of all ethnicities, but Hispanic individuals show a 1.5‐fold higher risk when compared to non‐Hispanic whites. Many AD risk biomarkers have been proposed but not much is known about how genetic elements control their expression. We used 2000 genome sequenced Mexican Americans from extended pedigrees to identify genetic regions associated with AD blood‐based biomarkers.

Method

A total of 70 Mexican American subjects were diagnosed as ADRD cases (h2 = 0.75, p = 2.6×10−5). We quantified plasma concentrations, using a QuanterixÒ elisa assay, of four AD candidate biomarkers AB40, AB42, TAU and NFL. We identified genomic regions associated with these biomarkers using a linear mixed model as implemented in SOLAR on a set of 28 million SNPs. Our genetic variance decomposition model is tailored for relatively rare diseases where extended pedigrees are available. Candidate SNPs identified were extensively annotated and their individual eQTL contribution to the expression of flanking genes defined.

Result

The heritability component of each AD biomarker was defined, and the most significant estimate observed for NFL (h2 = 0.33, p = 6.96×10−17). We tested the association between circulating tau and identified two genome‐wide significant associations for SNPs rs242557 (3.11×10−14) and rs242562 (1.34×10−13)(Figure 1). Both SNPs are common and located in the first and second introns of the gene MAPT, respectively, and are in a conserved region with chromatin accessibility for transcription factors, suggesting regulatory functions (Figure 2). We tested the association between both SNPs and flanking gene expression, identifying strong evidence of cis‐regulation with the expression of the antisense‐RNA (KANSL1_AS1) of the gene KANSL1.

Conclusion

The identification of genetic variants associated with AD biomarkers is key to providing a reliable and cost‐effective genetic test for AD risk for the Hispanic population. The gene KANSL1 encodes a subunit of a histone acetylation enzyme and has been associated with Koolen‐de Vries Syndrome and cognitive impairment. The genetic associations are promising, but demand an independent validation to confirm their impact for the AD risk estimation.
Associations of plasma GFAP, NfL, and p‐tau231 with early‐onset Alzheimer’s Disease pathology
Authors: Logan Paige E. , Dage Jeff L. , Hammers Dustin B. , Manchella Mohit K. , Eloyan Ani , Mundada Nidhi S. , La Joie Renaud , Iaccarino Leonardo , Fagan Anne M. , Foroud Tatiana M. , Zetterberg Henrik , Blennow Kaj , Koeppe Robert A. , Aisen Paul S. S , Carrillo Maria C. , Rabinovici Gil D. , Dickerson Brad C. , Apostolova Liana G.
Published: December 2023

Background

Increased levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 231 (p‐tau231) in plasma have been associated with late‐onset Alzheimer’s Disease (AD). The impact of these biomarkers in early‐onset AD (EOAD) is unclear and the novel plasma biomarker, p‐tau231, has not been studied in this population. We aimed to demonstrate the effect of each biomarker on EOAD pathology by investigating their associations with amyloid burden, tau burden, and gray matter density (GMD).

Method

183 EOAD participants from the Longitudinal EOAD study with available baseline plasma GFAP, NfL, p‐tau231, MRI, amyloid PET, and tau PET data were included (mean age = 58.7, 55.2% female, 54.1% APOE‐ε4 carrier, mean MMSE = 21.9). Voxel‐wise multiple linear regression models of amyloid PET, tau PET, and T1‐weighted MRI images yielded statistical maps with GFAP, NfL, or p‐tau231 as predictors. Covariates were hierarchically added: Model 1: age, sex; Model 2: age, sex and APOE‐ε4; Model 3: age, sex, APOE‐ε4 and MMSE. All models are displayed at a family‐wise error adjustment of p<.05.

Result

Higher levels of GFAP, NfL, and p‐tau231 were significantly associated with greater amyloid burden and tau burden. Higher levels of GFAP and NfL were also significantly associated with lower GMD. No significant associations were found for p‐tau231 and GMD (Figures 1, 2 & 3). When controlling for APOE‐ε4 carrier status, the effect of GFAP on amyloid burden was no longer significant (Figure 1). After additionally controlling for MMSE, the effects of NfL and p‐tau231 on amyloid burden were no longer significant, while the effects of all three biomarkers on tau burden were reduced but remained significant. In terms in of GMD, the effect of NfL survived correction for dementia severity, while the effect of GFAP did not.

Conclusion

These results suggest that all three plasma biomarkers show stronger associations with neurodegeneration (cortical atrophy and/or tau burden) than with amyloid burden. Furthermore, this study highlights the importance of plasma biomarkers for AD diagnosis and monitoring. Future work should investigate longitudinal associations and the mediational role of APOE‐ε4 and dementia severity.
Continuum of measurement: Reviewing the advantages and disadvantages of self‐administered remote cognitive tests and their examiner administered alternatives
Authors: Ho Emily
Published: December 2023

Background

Four in 10 older adults own a smartphone in their 60s and beyond (Pew Research; 2017). Correspondingly, there has been surging interest in using digital cognitive assessments remotely to inform clinical and research practice with older adults and more comparisons between self‐ and examiner‐administered tests are needed.

Method

As part of a larger study, 1120 adults completed a battery of remotely administered tests (Mobile Toolbox) and a subset of this sample completed examiner administered in‐person testing (NIH Toolbox Cognition Battery). Attention was given to making the sample reflective of the US 2020 Census during participant recruitment. Of the 1120 participants, the majority of the sample were female (57%) and Caucasian (72%) and had a mean age of 45 (SD = 21). In terms of education, equal percentages had high school (34%) or some college (34%).

Result

Cognitive tests of processing speed, language, executive function, attention, and episodic memory were administered via a trained examiner and correlates of these tests were self‐administered remotely via a smartphone. Using examples, we will show which aspects of cognitive assessment had the best correlations between remote self‐administration and face‐to‐face examination and which had lower correlations.

Conclusion

For geriatric individuals, remote assessments can be used to help over barriers for care, such as difficulty getting to the office location due to limited mobility or lack of transportation. Remote assessments reduce participant burden and expense and increase research accessibility for older adults. Capitalizing on the omnipresent nature of internet‐connected devices, this improves opportunities to remotely monitor other dimensions relevant to cognition using smartphone apps and wearable sensors. In addition to improving access to testing, digitally administered assessments dramatically improve some individual’s tolerance to testing with shorter tests that can be administered via computer adaptive testing (CAT). Despite these benefits, some aspects of the cognitive assessment cannot be adequately replicated remotely and thus yield lower correlations to their examiner‐administered alternatives. Clinical and research implications are discussed.
Mobile Toolbox cognitive tests: validity and reliability in three samples
Authors: Nowinski Cindy J. , Kaat Aaron J. , Novack Miriam , Slotkin Jerry , Hosseinian Zahra , Adam Hubert , Gershon Richard C.
Published: December 2023

Background

The Mobile Toolbox (MTB), an app‐based assessment platform, enables completely remote, self‐administered assessment using participants’ own smartphones. We present psychometric evidence for eight MTB cognitive measures assessing language, working memory, episodic memory, executive function, and processing speed.

Method

Three samples were used to evaluate convergent validity, age‐related change, internal consistency and test‐retest reliability. Sample I consisted of 94 adults ages 18‐85 who were administered “gold standard” cognitive measures followed by self‐administered MTB. Sample II, recruited for norming, included 1,020 participants ages 18‐90 who completed MTB measures remotely. Sample III was a convenience sample of 800 participants who completed MTB remotely with retest after 7, 14, or 21 days. Pearson correlation coefficients between MTB and external measures were used to evaluate convergent validity. Internal consistency was evaluated using measure‐appropriate tests: split‐half reliability, Cronbach’s alpha or IRT‐based indices. For measures with timing‐dependent scores, separate analyses were performed for iOS and Android devices. Spearman correlation coefficients were calculated to evaluate relationships between age and test scores.

Result

Convergent validity data from Sample I (64% female, 52% white, 99% non‐Hispanic, age = 48+/‐18) revealed moderate to strong correlations between MTB test scores and performance on external measures of similar constructs (Table 1). Table 2 shows results derived from Sample II (44% female, 13% Hispanic, 74% white, age = 45+/‐22). Internal consistency estimates ranged from 0.69 to 0.98. On timed tests, Shape‐Color Sorting and Arrow Matching showed significant score differences between Android and iOS devices when controlling for age. However, internal consistency was equivalent between the two, as indicated by overlapping confidence thresholds (Table 3). Performance on executive function, processing speed, and some memory tasks negatively correlated with age. Word Meaning scores improved with age while Spelling remained stable. Test‐retest reliability, using preliminary Sample III data, ranged from 0.47 (memory tests) to 0.86.

Conclusion

Initial studies, using three diverse samples, support the validity and reliability of the first eight MTB cognitive measures. MTB tests showed satisfactory internal consistency and convergent validity and most measures correlated with age in the expected directions. Our results support the use of MTB in cognitive research.
Assessing risk taking and decision making associated with late‐life onset mild psychotics symptoms in cognitively normal older adults
Authors: Ismail Zahinoor , Aarsland Dag , Ballard Clive G , Corbett Anne , Creese Byron
Published: December 2023

Background

Late‐life onset psychosis assessed in the Mild Behavioral Impairment framework (MBI‐psychosis) is a risk factor for dementia and known to be associated with impaired reasoning and memory in people without dementia. There is evidence that psychotic symptoms across diagnostic boundaries share some common genetic and neuropsychological correlates. In this study we aimed to determine whether MBI‐psychosis is associated cognitive deficits typically associated with other psychoses. To do this, we examined the relationship between MBI‐psychosis and scores on a specialised decision making and risk‐taking test, the Cambridge Gambling Task (CGT), performance on which is impaired in people with earlier life psychotic syndromes.

Method

476 participants were drawn from the online PROTECT registry on the basis of the Mild Behavioural Impairment Checklist (MBI‐C) ratings indicating psychosis and invited to complete the Cambridge Gambling Task. The association between performance on six CGT outcome measures, assessing elements of risk taking and decision making, and MBI‐psychosis was tested using linear regression (controlling for age, sex and education level).

Result

Overall, there was little evidence of a substantial impact of MBI‐psychosis on CGT scores. Our study was powered to detect medium effect sizes. We found modest evidence of higher risk taking associated with more severe MBI‐psychosis scores (β = ‐0.1, SE = 0.05, p = 0.04) but this did not survive multiple testing correction.

Conclusion

This is the first time a specialist decision making and risk‐taking test has been conducted in MBI‐psychosis. Although MBI‐psychosis is associated with a range of cognitive impairments in later‐life and dementia risk it appears that any shared neuropsychological basis with other psychoses is limited (though we cannot rule out a small non‐clinically significant effect size). This has possible implications for the diagnostic classification of later‐life onset mild psychotic symptoms.
Identification of pathogenic SORL1 genetic variants in Alzheimer’s disease patients
Authors: Holstege Henne
Published: December 2023

Background

An estimated ∼2‐3% of early‐onset Alzheimer’s disease (AD) patients carry a predicted rare damaging variant in the SORL1 gene, which encodes the SORLA receptor protein. While protein‐truncating variants (loss‐of‐function, LOF) occur almost exclusively in AD patients, the large majority of damaging variants are missense variants. However, the effect of individual missense variants on AD risk varies widely, warranting a variant pathogenicity screen.

Methods

We prioritized genetic variants in SORL1 by investigating to what extent they lead to familial disease when they occur in protein homologs. We used a sample of 18,959 non‐related AD cases from the ADES/ADSP studies to investigate the age‐at‐onset in carriers of a prioritized SORL1 variant relative to WT SORL1 in context of APOE genotype. Second, since functional SORLA is cleaved at the neuronal membrane into soluble SORLA (sSORLA) we used Western Blot and proteomics to test whether SORL1 variants affected the level of sSORLA in CSF.

Results

Compared to SORL1 wild type AD patients, carriers of prioritized SORL1 variants had an expedited age at onset similar to carriers of LoF variants: of those homozygous for APOE‐ε4 who carried a prioritized SORL1 variant, 80% had AD by age 61 (95%CI 60‐NA, n = 6) compared to 73 for WT‐SORL1 carriers (95%CI 72‐73, n = 1091). Of those heterozygous for APOE‐ε4 who carried a prioritized SORL1 variant, 80% had AD by age 71 (95%CI 68‐76, n = 62) compared to age 78 WT‐SORL1 carriers (95%CI 78‐78, n = 4816). Of those negative for the APOE‐ε4 allele with a SORL1 variant, 80% had AD by 83 years (95%CI 78‐90, n = 54) compared to 85 years for WT‐SORL1 carriers (95%CI 85‐85, n = 5773). These effects were absent for non‐prioritized missense variants. Second, using WB we found that sSORLA levels in carriers of pathogenic missense variants were reduced to ∼50% relative to carriers of benign SORL1 variants, while levels of truncating SORL1 variants were reduced to ∼65%.

Discussion

Prioritizing SORL1 missense variants according to variant‐effects in protein homologs leads to variants that expedite the age‐at‐onset independent of APOE background. Carriers of pathogenic missense or truncating variants have low CSF‐sSORLA levels, which may serve as a biomarker for impaired SORL1.
Researcher turned care partner: Perspectives on lived experience of navigating ADRD
Authors: Gelmon Sherril B
Published: December 2023

This presentation will illustrate the lived experience of a health services researcher who was a care partner for her husband with ADRD. This couple engaged for 11 years with an academic Alzheimer’s center for clinical management and participation in several clinical trials. This care partner was motivated to care out of love and concern, learning by doing and taking on unfamiliar responsibilities. Few people understood the personal time commitment and challenges, and the hours of vigilance to ensure her husband was safe, healthy, and living at home with dignity. She was challenged to maintain her scholarly career.

The needs of care partners are often unmet. Caring for a family member can lead to psychological and physical distress. Personal experience highlighted the need for information about ADRD progression, financial and legal advice, routine and respite care, and psychological support. Support programs did not address the advanced stages of disease. COVID‐19 reduced supports and increased isolation. This care partner learned to effectively support and care while navigating the Alzheimer’s disease delivery and research systems, and identifying relevant resources to support the family dyad. Since the husband’s death, the researcher has refocused her research agenda to study strategies, policies and mechanisms to enable care partners, clinicians and researchers to coproduce care systems that better support care partners.

This researcher’s experience highlights the need to recognize and value the essential role the care partner plays in supporting the person with ADRD. Care partner resources are frequently determined and designed by expert health and social service providers. Person‐centered health initiatives are enhanced through coproduction where patients, partners, and clinicians develop, deliver, assess and improve the relationships and actions that contribute to the health of the person with ADRD.

Coproducing care and support for a person with ADRD requires actively engaging the care partner to represent their personal dyad, and inviting them to articulate the resources, services and supports they need to navigate their journey as a care partner that will complement clinical care. This presentation will frame the context for the three presentations that follow, illustrating approaches to effectively coproducing ADRD care.
Lipopolysaccharide aggravates depressive‐like behavior via increasing microglial inflammation, decreasing microglial ramification, and altering tryptophan level in obese rats
Authors: Chunchai Titikorn , Chinchapo Thirathada , Pintana Hiranya , Arunsak Busarin , Janjek Sornram , Kerdphoo Sasiwan , Nawara Wichwara , Thonusin Chanisa , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: December 2023

Background

Long‐term high‐fat diet consumption has been shown to induce endotoxemia, microglial dysmorphology, and depressive‐like behavior (1, 2). Previous studies demonstrated that the kynurenine pathway of tryptophan metabolism plays an important role on mediating the depressive‐like behavior in response to inflammation (3, 4). However, the effects of lipopolysaccharide as endotoxin on the alterations of microglial profiles/morphologies, changes in brain metabolites, as well as depressive‐like behavior in obese condition have never been investigated.

Method

Sixteen male Wistar rats were randomly divided into two groups to fed with either normal diet (ND, n = 8) or the high‐fat diet (HFD, n = 8) for 12 weeks. At week 12, animals in each dietary group were subsequently divided into two subgroups (n = 4 per subgroup) to receive either a single dose of vehicle (1 ml of 0.9% normal saline solution, intraperitoneal (i.p) injection, or lipopolysaccharide (LPS, 0.5 mg/kg, i.p. injection). After the injections for 12‐16 hours, all animals were measured depressive‐like behaviors and blood was collected. Then, animals were sacrificed, and brains were obtained for further molecular investigation.

Result

We found that LPS‐treated HFD‐fed rats, not LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats, increased microglial IL‐1β mRNA level (p<0.05, Figure 1). In addition, LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats significantly decreased microglial ramification as indicated by decreasing branch points, whereas LPS‐treated HFD‐fed rats showed the lowest microglial branch points (p<0.05, Figure 1). The level of brain tryptophan and depressive‐like behavior increased in both LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats, when compared with those of vehicle‐treated ND‐fed rats (p<0.05, Figure 1). Interestingly, LPS‐treated HFD‐fed rats showed the highest brain tryptophan level and freezing duration during Force Swimming Test (FST) (p<0.05, Figure 1).

Conclusion

These findings indicate that LPS aggravates depressive‐like behavior in obese condition by increased microglial hyperactivation, and possibly be related to its regulation of kynurenine metabolism.
What do public high school teachers in Nigeria know about dementia?
Authors: Olaniyi Olajumoke , Ogunyemi Adedoyin O , Olusanya Adedunni W
Published: December 2023

Background

The number of dementia cases is projected to triple in the next 20‐25 years with majority of the increase in developing countries including Nigeria. Teachers can act as excellent educators by playing a key role of delivering important health education messages to students that target early adoption of healthy behaviours and reduce stigma. However, there is no assessment of school teachers’ understanding of dementia in Nigeria.

Method

This was a cross‐sectional study of 300 high school teachers, aged 18 years or older, and working in public schools in Lagos, Nigeria. A 14‐item questionnaire with yes/no or don’t know responses was used to assess their knowledge about dementia from June to November 2022. The data obtained were analysed using IBM Statistical Package for Social Sciences (SPSS) Version 25.

Result

The mean age of respondents was 42.9 ± 9.9 years and 59.3% of them were females. The majority (81.0%) had heard about dementia and 32.0% knew someone with dementia. The mean score for knowledge about dementia was 7.4 ± 0.2 points out of 14 points. More than half of the respondents (56.0%) reported that dementia is a normal part of ageing, 29.7% considered dementia to be a mental illness, and a half (50.0%) of the participants did not know if dementia could be cured. The level of dementia knowledge was not significantly associated with age or with education level.

Conclusion

Our results suggest that the teachers had a fair knowledge of dementia. There is a need to better educate school teachers and improve their knowledge about dementia. Emphasis on the risk factors, prevention, and symptoms of dementia should be included in the educational content.
Systematic Review on the Social Participation Assessment Tool for Older Adults
Authors: Lee Hamin , Kim Mi Kyeong , Park Hae Yean , Yun Sohyeon , An Hyun Seo , Kim Inhye
Published: December 2023

Background

Due to the extension of the life expectancy of the elderly population, the importance of living healthy rather than simply leading a life in old age is emphasized. It is difficult to maintain social participation for older adults because most of them experience the termination of work or childcare which have been their major life roles. Considering that social participation is a factor that has a multifaceted effect on the health of older adults, it is necessary to understand and promote older adults’ social participation. This systematic review aims to analyze the literature using social participation assessment tools for older adults and presented the frequency of use, assessment items, and methods of each assessment.

Method

Using databases from Pubmed, Medline, CINAHL, and Web of Science, a total of 2,423 studies were collected. 18 studies were selected according to the selection and exclusion criteria.

Result

9 studies (50%) were published in the last five years. In the case of research design, 12 studies (66.6%) were designed as cross‐sectional survey studies, which were found to be the most common. There were a total of 11 assessment tools for older adults’ social participation among 18 studies. The most widely used assessment tool was Assessment of Life Habits (LIFE‐H), which was used in a total of 7 studies (38.9%). It was found that the components were different for each tool. Most of the assessment tools were in the form of self‐reporting questionnaires. Frequency of the participation was the most common method. Others asked the degree of difficulty and a number or status of participating activities.

Conclusion

In this study, a total of 18 pieces of literature were reviewed to analyze the assessment tool that measured the social participation of older adults of 65 and above. A total of 11 assessment tools were derived, and LIFE‐H was the most frequently used. Through this study, it is expected that clinicians or researchers can help when judging and selecting social participation assessment tools, and that appropriate tool selection can lead to a better understanding of the social participation of older adults.
Integrated Primary Care Model Prevents Hospitalizations for People Living with Dementia
Authors: Clevenger Carolyn K , Medders Laura J , Khakharia Anjali , Moore Miranda
Published: December 2023

Background

People living with dementia (PLWD) have high rates of total and ambulatory care sensitive hospital admissions and emergency department utilization. Ambulatory care sensitive hospital admissions are those that could be avoided by robust outpatient care. The Integrated Memory Care (IMC) is a comprehensive dementia care model where patients and their family caregivers access dementia‐sensitive geriatric primary care.

Methods

We conducted a retrospective observational study of adult patients of IMC, Cognitive Neurology (CN), and Primary Care (PC) clinics aged 65 and older with a diagnosis of dementia in 2019‐2021. We matched patients by age, gender and race and measured the risk of hospitalization using logistic regressions controlling for clinic. Additionally, we conducted a regression adjusted for state of illness (proxied by activities of daily living (ADL)) for the IMC and CN clinics.

Results

Overall 509 patients seen in IMC were matched with 490 CN patients and 509 PC patients. Most patients were female and white and aged 70‐85. IMC patients had higher overall ADL scores than CN indicating more functional dependence. CN [PN] had 10% [2 times] higher odds (Odds Ratio (OR): 1.107; 95% Confidence Interval (CI): 0.87‐1.41; OR: 2.037; 95% CI: 1.440‐2.882), when compared to IMC patients in unadjusted models. After adjusting for ADL scores, CN patients had 66% higher odds (OR: 1.662; 95% CI: 1.260‐2.193) of having a hospital admission during the study period.

Conclusions

Dementia‐sensitive primary care reduces the rate of total and ambulatory‐sensitive hospitalizations reducing healthcare costs and causing less disruption to care.