bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring technology use as an instrumental activity of daily living in those with late life cognitive disorders
Authors: Benge Jared F 
Published: January 2025

AbstractBackgroundOlder adults increasingly rely on digital technologies to perform instrumental activities of daily living (iADLs), including commerce, managing accounts online, using texting and websites for social connection, and accessing health services via web platforms. Despite the increasingly central role of technology to daily life, current iADL measures do not regularly capture the digital approach to daily activities. The current study had three broad aims 1) determine the applicability of technology‐based iADLs to the daily lives of older adults being evaluated for Alzheimer’s disease and related dementias (ADRD), 2) compare the level of dependence for tech and traditional iADL items, and 3) determine if adding technology related iADL items improves the diagnostic accuracy of iADL assessments.Methods264 care partners (58.7% spouses) of older adults referred for evaluations of cognitive disorders (34.5% with MCI; 51.9% with dementia) completed the Functional Activities Questionnaire (traditional ADL measure) and 11 technology‐based iADL items (i.e. remembering passwords, managing online accounts, using a device for messaging, etc.).ResultsRates of “not applicable, never did” were uncommon for technology‐based items, including microwave use (3.8%), smartphone use for calls (5.3%), and remembering passwords (8.3%). Increasing age and decreasing education predicted more not applicable responses to technology items. Average dependence ratings of technology items were less than for traditional ADLs (t(263) = 4.29, p<.0001; figure 2), and increased as a function of ADRD severity. Adding technology ‐based items marginally increased diagnostic accuracy of ADL measures for detecting dementia (AUC .85 vs. .83; z = ‐2.07, p = .03).ConclusionsTechnology use amongst older adults presenting for evaluations of cognitive decline is common for a range of daily activities. That being said, a digital divide still exists, with older age and less education predicting less applicability of technology‐based iADLs. Despite stereotypes to the contrary, overall degree of dependence for technology was less than for traditional, largely analog based iADLs, likely due to the ability to automate some tasks (i.e., automatic bill pay). We discuss how these findings broadly fit in the larger technological reserve hypothesis, implications for clinical assessment of iADLs, and approaches for future proofing iADL measures.
Novel VCP gene mutation in three siblings with frontotemporal dementia and amyotrophic lateral sclerosis in a Turkish family
Authors: Gultekin Murat , Basak Ayse NazlI 
Published: January 2025

AbstractBackgroundValosin Containing Protein (VCP) mutations are responsible some genetic etiologies of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).MethodA 67‐year‐old, male patient, applied to the clinic due to behavioral changes and difficulty swallowing. According the patient history it was reported that his first complaint started 6 years ago (at the age of 61). The patient’s irritability, behavioral and character changes increased over time. The patient consulted a psychiatrist and diagnosed depression then, antidepressant treatment was started.Genetic investigation was performed for the preliminary diagnosis of FTD‐ALS association. First, the C9orf72 gene report was normal. Then, all exon sequencing was performed. A heterozygous missense mutation p.Arg453Trp (c.1357C>T) was detected in the 11th exome of the VCP gene. This mutation, which was identified for the first time, was also detected in the other two sisters of the patient who had similar complaints.ResultThe patient’s premorbid personality traits were conservative, helpful, social and interested in his family. However, it has been stated that in recent years his sexual desire has increased and he has been making inappropriate conversations in social environments. Difficulty in swallowing was added to the complaints within a year, and in the last two years, speech disorder such as slurring words, increase in appetite, desire to travel and spending money were added.There was no known history of neuropsychiatric disease in his parents. Three of the four siblings had a similar clinical picture. On examination, the patient’s speech was dysphonic, fasciculation and atrophy was seen in the tongue. 4/5 motor muscle strength in the neck muscles were detected. There was bilateral Hoffman positivity and deep tendon reflex brisk in the lower extremities. Swallowing reflexes could not be obtained. Brain magnetic resonance imaging scan revealed atrophy in the frontotemporal regions. ENMG examination was compatible with motor neuron disease.ConclusionALS and FTD have been considered for many years as two different pathologies with distinct pathology. But, in recent years some studies have revealed that these disorders belong to a continuum, the so‐called ALS‐FTD spectrum disorders. Many causative genes are shared in both diseases.
What can animal studies tell us about EWB and AD
Authors: Wang Kuan Hong 
Published: January 2025

AbstractEmotional well‐being (EWB) is considered to play an important role in the health of individuals over their lifespan. Clinical studies suggest an association between EWB and the risk or progression of AD. However, the mechanistic link and causal relationship between EWB and AD remain unknown, due to limited experimental access and control of the underlying brain processes in human. Animal models offer powerful tools for neural circuit analysis and control of AD genetic risk factors, but subjective feelings of EWB cannot be assessed through self‐report. To study EWB across species, we adopt a conceptual framework that views emotions as measurable states of brain networks that integrate exteroceptive and interoceptive affective stimuli and cause multiple cognitive, somatic and behavioral changes. Moreover, recent neuroanatomical and functional imaging studies have revealed evolutionarily conserved brain circuits, including mesocortical association areas and their connections with subcortical limbic areas, underlying the experienced and evaluative components of EWB. We will review recent progress in animal models to elucidate the functional activities of these circuits in emotional processing, the vulnerability of these circuits to AD pathology, and potential neuromodulation strategies to improve circuit functions. We will also offer our perspectives on the challenges and opportunities to link these neural representations to EWB and AD risk.
Long Pause Ratio in Speech Reflecting Dementia Severity and Hippocampal Atrophy in Early Alzheimer's Disease
Authors: Lin Bo‐Xiang , Chou Chia‐Ju , Chang Chih‐Ting , Lee Chia‐Ying , Fang Chuang Yi‐ , Chiu Yen‐Ling , Liu Yi‐Chien 
Published: January 2025

AbstractBackgroundIt has been found that speech analysis is a sensitive method for early Alzheimer’s disease (AD) detection. Among the various linguistic features, silent pause has emerged as a fair indicator, exhibiting higher prevalence in individuals with AD compared to general population. This study aimed to further examine the relationship between long pause ratio (LPR) in speech and traditional markers of disease progression, like biomarkers, neuroimaging features and neuropsychological tests.MethodSince 2021 to 2023, we recruited 104 participants from memory clinic of Cardinal Tien hospital, Taipei, Taiwan. All participants received amyloid PET, 3.0 T brain MRI, and comprehensive neuropsychological tests. The determination of amyloid positivity came from consensus visual rating and quantitative methods utilizing SUVR (standardized uptake value ratio). Speech samples were collected using the picture description test, in which the participants describe three Taiwanese‐culture‐based pictures in one minute. LPR was defined as the number of pauses greater than two seconds divided by the number of words.ResultThe research study revealed a distinct pattern, with LPR being highest with AD (mean: 0.02), followed by aMCI (mean: 0.01), and nearly zero with normal controls (AD vs aMCI: p = 0.033; aMCI vs Normal: p<0.001). There was also positive correlation between LPR and CDR‐SB (p<0.001) as well as other cognitive tests such as MMSE (p = 0.001) and CASI (p = 0.003), and negative correlation between LPR and hippocampus volume (p<0.001). In multiple regression analysis, our study further showed that LPR alone, could effectively predict CDR‐SB and hippocampus volume (CDR‐SB: β = 57.01, t = 2.93; hippocampus volume: β = ‐21.90, t = ‐3.63). However, no association between LPR and amyloid burden has been found.ConclusionLong pause ratio appears rarely in normal controls of our participants. However, LPR increases as the severity of dementia worsens. Moreover, it also correlates with hippocampal size in our cohort. LPR should be considered as a critical linguistic feature in speech analysis.
Leveraging a multi‐day learning paradigm to reveal early amyloid‐ and tau‐ related cognitive deficits in preclinical Alzheimer’s disease
Authors: Jutten Roos J , Soberanes Daniel , Molinare Cassidy , Hsieh Stephanie , Farrell Michelle E. , Rentz Dorene M , Marshall Gad A , Johnson Keith A , Sperling Reisa A , Amariglio Rebecca E , Papp Kathryn V 
Published: January 2025

AbstractBackgroundIndividuals with preclinical Alzheimer’s disease (AD) show reduced practice effects on annually repeated neuropsychological testing, suggesting a decreased ability to learn over repeated exposures. Remote, digital testing enables the assessment of learning over more frequent time intervals, thereby facilitating a more rapid detection of those early learning deficits. We previously showed that multi‐day learning on the Boston Remote Assessment for Neurocognitive Health (BRANCH) was indeed diminished in Αβ+ cognitively unimpaired (CU) older adults. Here, we further investigated the impact of tau pathology on BRANCH multi‐day learning curves (MDLCs).MethodN = 136 CU older adults (age = 73.4±7.6, 66% female, 16.6±2.4 years education) from three well‐characterized cohorts completed multi‐day BRANCH on their personal device. The assessment includes two associative memory tests (Face Name and Groceries Prices) and a processing speed test with an associative memory component (Digit Signs) with identical stimuli repeated for seven consecutive days. An MDLC score is computed using an area under the curve method allowing for the combination of day 1 performance with a non‐linear learning trajectory over the subsequent six days. All participants had [11C]Pittsburgh compound‐B and [18F]flortaucipir PET within 0.7±0.5 years of BRANCH and were classified as A ± (global amyloid burden, DVR cutoff 1.14) and T ± (inferior‐temporal tau SUVr, cutoff 1.30), resulting in n = 91 A‐T‐, n = 29 A+T‐ and n = 16 A+T+. Linear regression analyses adjusting for age, sex, and education were used to examine differences in BRANCH day 1 and MDLC scores across A/T groups.ResultNo A/T group differences were detected using day 1 scores. However, MDLC scores increasingly diminished across groups, with the A+T‐ group performing marginally worse (ß = ‐0.04,95%CI[‐0.08–0.01], p = 0.11) and the A+T+ group significantly worse (ß = ‐0.06,95%CI[‐0.11–0.01], p = 0.03) than A‐/T‐ (Figure 1). A+ status regardless of T‐status was associated with diminished Digit Signs MDLCs, whereas being T+ drove worse performance on Face Name and Groceries Prices MDLCs (Table 1).ConclusionSubtle differences in learning among CU older adults with different A/T biomarker profiles are observable using MDLCs. These findings further support the notion that a multi‐day learning paradigm can provide unique information about cognition that is not captured using a single time‐point assessment and is particularly relevant in preclinical AD.
How do short‐term practice effects compare to biomarkers of Alzheimer’s disease?
Authors: Duff Kevin , Hammers Dustin B. , Koppelmans Vincent , King Jace B , Hoffman John M. 
Published: January 2025

AbstractBackgroundPractice effects on cognitive testing in Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. The current study sought to add to this growing literature.MethodCognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) repeated a brief battery of cognitive tests twice across one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE e4 status.ResultThe intact participants showed significantly larger practice effects than the other two groups on an overall composite measure, and those with MCI showed significantly larger practice effects than those with AD. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact>MCI>AD). For APOE e4, the intact had significantly fewer copies of e4 than MCI and AD. Overall, the effect sizes of practice effects were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons (see Table).ConclusionShort‐term practice effects on cognitive tests appear to be a sensitive marker in late life cognitive disorders, as they separated groups better than commonly‐used biomarkers in AD. Further refinement of short‐term practice effects as a tool for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.
Examining Practice Effects at Multiple Retest Intervals in Older Adults at Risk for Alzheimer's Disease
Authors: Wilks Hannah M , Welhaf Matthew S. , Aschenbrenner Andrew J. , Cruchaga Carlos , Morris John C. , Hassenstab Jason J. 
Published: January 2025

AbstractBackgroundPractice effects (PEs) on cognitive tests are improvements in performance from repeated testing. We and others have shown that reductions in PEs on standard tests administered annually are associated with neurodegenerative disease. Using mobile technology, cognition can be assessed at much higher frequencies than standard in‐clinic assessments. These high‐frequency assessments offer a unique opportunity to measure PEs at multiple timescales, including retest intervals across months, weeks, days, within‐day, and even trial‐to‐trial. It is unclear if PEs observed across these different retest intervals are equally sensitive to clinical status and genetic risk of Alzheimer’s disease (AD).MethodWe examined timescales of PEs using a very brief, smartphone‐based processing speed test in 399 well‐characterized older adults (Table 1). Cognition was assessed four times per day over a week every six months for up to 2.5 years. PEs from the task were modeled at multiple timescales, including biannually, weekly, daily, and at the trial level. Additional mixed effects models compared PEs across clinical status and genetic risk for AD.ResultAcross all 399 participants, there were significant practice effects at all timescales, with an average improvement in speed of 0.10s over a 6‐month retest interval, 0.02s within each day of testing, and 0.005s each individual testing session. Performance improved throughout each week, and the most performance gains occurred on the first day of testing. Comparing clinical status using the Clinical Dementia Rating (CDR®) revealed that CDR>0s had significantly slower overall processing speed (Cohen's d = 0.9) than CDR0s, however, CDR>0s displayed much more performance gains than CDR0s on their first three days of testing (Figure 1; d = 1.4). Across biannual visits, CDR>0s lost more performance gains than CDR 0s, indicating less retention over time. Comparing APOE e4 carriers and e4 noncarriers revealed similar patterns. Carriers of the e4 allele were slower than noncarriers (d = 0.3) and lost more performance gains across biannual visits.ConclusionMagnitudes of PEs across multiple retest intervals are sensitive indicators of clinical status and genetic risk for AD. PEs observed at the daily level appear to be the most sensitive to clinical status and genetic risk for AD.
Association between short‐term memory binding performance and tau burden in the medial temporal lobe
Authors: Huyghe Lara , Quenon Lisa , Salman Yasmine , Colmant Lise , Gérard Thomas , Malotaux Vincent , Boyer Emilien , Dricot Laurence , Lhommel Renaud , Ivanoiu Adrian , Hanseeuw Bernard J 
Published: January 2025

AbstractBackgroundThe ability to discriminate very similar objects by implementing the binding between their multiple features is assumed to be supported by the medial temporal lobe (MTL). MTL is the first brain region that shows abnormal tau accumulation in Alzheimer’s disease (AD). However, whether binding ability is impaired since the preclinical stage of AD and relates to MTL tau burden is not well‐established.MethodWe included 35 amyloid‐negative cognitively normal individuals (Aβ‐CN), 16 amyloid‐positive CN (Aβ+CN) and 17 Aβ+ individuals with Mild Cognitive Impairment (Aβ+MCI). Aβ status was determined using lumbar punction or [18F]‐Flutemetamol Positron Emission Tomography (PET). Participants underwent a [18F]‐MK6240 tau‐PET to quantify tau burden in the MTL (entorhinal cortex, hippocampus, parahippocampus). They performed the Visual‐Short‐Term‐Memory‐Binding‐Test (VSTMBT), a test which is underpinned by the proper functioning of the MTL (Parra et al., 2010) and assess the ability to discriminate perceptually close items. In VSTMBT, participants had to determine whether a set of shapes was identical to the set presented before a 900ms blank retention interval. There were 4 conditions in which the number of shapes (2 or 3) and the color (white = ”Shape‐Only Condition” or colored) of the shapes varied. The colored conditions implied to memorize the binding between shapes and their respective color (“Binding‐Condition”)(Figure.1). We calculated the accuracy score (AS) and the mean reaction time (RT) for each condition.ResultAS was lower in both Aβ+ groups than in Aβ‐CN participants in all conditions except the Shape‐Only‐2‐items, while Aβ+CN and Aβ+MCI did not differ (Figure.2). The Aβ+CN group was slower than Aβ‐CN only in the Binding‐2‐items‐Condition.Total AS was associated with MTL tauopathy over the entire sample (even after controlling for age and education) and when restricting to all CN participants. Finally, MTL tauopathy was more associated to AS in the Binding‐Condition than in the Shape‐Only‐Condition (Figure.3).ConclusionImpaired visual short‐term memory performance was evidenced since the preclinical stage of AD, including in Binding‐Condition. Performance in Binding‐Condition was related to tau burden in the MTL, suggesting that impairment in visual short‐term memory binding abilities may constitute an early cognitive marker of accumulating tau pathology in the MTL.
Social determinants of health and not global genetic ancestry predicts cognitive performance and dementia risk in Latinos
Authors: Llibre‐Guerra Jorge J. , Jiang Miao , Acosta‐Castillo Isaac , Ortiz Ana Luisa Sosa , Acosta Daisy M , Velazquez Ivonne Z. Jimenez , Guerra Mariella , Salas Aquiles , Rodriguez‐Salgado Ana M , Guerra Juan C Llibre , Sánchez Nedelys Díaz , Prina Matthew , Renton Alan E. , Yokoyama Jennifer S. , Llibre‐Rodriguez Juan J. ,   1066 Dementia Research Group
Published: January 2025

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) disproportionately affect Latinos compared to non‐Latino whites. Leveraging the non‐monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD disparities within Latinos, focusing on genetic ancestry and SDoH.MethodCommunity‐dwelling participants aged 65 and older (n = 4000) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments, including sociodemographic and risk factors questionnaire, neurological exam, cognitive assessment, and blood draw. Dementia was diagnosed using the cross‐culturally validated 10/66 algorithm. Individual admixture proportions were determined using sixty ancestry‐informative markers. To evaluate the effect of global ancestry on dementia and cognitive performance, we used multivariate linear regression models adjusted for SDoH (e.g., gender, education level, socioeconomic status (SES), rural area, and vascular risk factors).ResultWe observed extensive three‐way (African/European/Native American) genetic ancestry variation between countries (Figure 1). Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower SES (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). As a result, in unadjusted analysis, individuals with predominant African ancestry exhibited a higher dementia frequency (p = 0.03) and both Native American and African ancestry predominant groups showed lower cognitive performance relative to those with higher European ancestry (p<0.001). However, after adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [‐0.19, 0.59] and Native predominant p = 0.74 [‐0.24, 0.33]).ConclusionWe report a comprehensive characterization of the role of global genetic ancestry in cognitive performance and dementia in Latin America while controlling for SDoH. In our study, adjustment of SDoH attenuated associations between genetic ancestry, dementia probability, and cognitive performance. These findings highlight that social and environmental factors likely play more critical roles than genetic ancestry in determining racial/ethnic disparities in cognitive performance and subsequent dementia risk.