bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the correlation between informant ratings of function and cognitive assessment scores differ based on informant gender?
Authors: Stradtman Megan , De Vito Alyssa N. , Price Ashley N. , Strenger Jennifer , Thompson Louisa I. , Sinoff Stuart , Snyder Peter J. , Alber Jessica 
Published: January 2025

AbstractBackgroundInformant reports can complement standardized cognitive assessment and improve accuracy of dementia diagnosis. Although informant reports correlate moderately with objective measures of decline, the influence of informant factors, such as gender, on these relationships is unclear. This study assessed the hypothesis that informant gender would emerge as an independent predictor in the relationship between informant ratings of cognitive function (i.e., Clinical Dementia Rating Scale) and cognitive assessment scores.Method204 adults aged 55‐80 (124 F, 80 M) completed the CDR with study partners (106 F, 95 M). Participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and CDR at screening, and the Free and Cued Selective Reminding Test (FCSRT) within 12 weeks of screening. RBANS delayed memory index scores were available for 203 participants, and the RBANS total scores for 200 participants. 148 participants had FCSRT immediate free recall and delayed free recall scores available. Linear regression analyses were used to evaluate whether informant gender significantly predicted the relationship between the CDR sum of boxes (SOB) and: RBANS total score, RBANS delayed memory index score, FCRST immediate recall score, and FCRST delayed recall score, while controlling for age and education.ResultThe CDR SOB was negatively associated with RBANS total score (R2 = .547, β = ‐.511, p< .001), RBANS delayed memory index score (R2 = .640, β = ‐.643, p< .001), FCRST immediate free recall (R2 = .220, β = ‐.162, p = .025), and FCRST delayed free recall (R2 = .667, β = ‐.646, p<; .001). Informant gender was not associated with any cognitive outcome (p’s> .05).ConclusionThese results did not support the hypothesis that participants with female study partners would show a stronger correlation between informant ratings of cognitive function and cognitive assessment scores. Future work will: 1) use qualitative analysis to investigate potential gender differences in informant reporting and 2) examine additional informant‐related factors that may impact the relationship between informant ratings and neuropsychological testing such as informant level of education, culture, and family history and/or experience with dementia.
Heterogeneous clinical phenotypes of sporadic Early‐onset Alzheimer’s disease: A data‐driven approach
Authors: Putcha Deepti , Katsumi Yuta , Touroutoglou Alexandra , Dage Jeffrey L. , Eloyan Ani , Nudelman Kelly N. , Carrillo Maria C. , Rabinovici Gil D. , Apostolova Liana G. , Dickerson Bradford C. , Hammers Dustin B. , Consortium LEADS 
Published: January 2025

AbstractBackgroundEarly‐onset Alzheimer’s disease (EOAD) manifests prior to the age of 65. Clinical presentation of EOAD is distinct from that of late‐onset Alzheimer’s disease, and is characterized as having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS) described their sample as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the range of EOAD presentation, we applied a neuropsychological data‐driven method to phenotypic subtyping within the LEADS cohort.MethodData from 169 amyloid‐positive EOAD participants with composite data in all cognitive domains (Episodic Memory, Executive Functioning, Speed/Attention, Language, and Visuospatial) were analyzed. Our approach consisted of comparing the relative levels of baseline impairment in each cognitive domain. Education‐corrected normative comparisons were made using a sample of 98 aged‐matched cognitively normal participants. A cut‐off of 1 SD below all other composite domain scores was applied to indicate a phenotype of “predominant” impairment in a given cognitive domain. Individuals were otherwise considered to have a phenotype best characterized by multidomain impairment.ResultWe identified 6 phenotypic subtypes of EOAD (Table 1): Dysexecutive‐predominant (22% of sample), Amnestic‐predominant (11%), Language‐predominant (11%), Visuospatial‐predominant (15%), Mixed Amnestic/Dysexecutive‐predominant (11%), and Multidomain (30%). These subtypes did not differ on age, age‐at‐symptom‐onset, sex, or overall clinical severity (p>0.05). Groups differed on global cognitive functioning (MMSE) such that the Amnestic‐predominant group performed better than other domain‐predominant subtypes of EOAD (p>0.05). In contrast to the heterogeneity observed from our data‐driven approach, diagnostic classifications for this same sample based solely on clinical judgment indicated that 82% of individuals were amnestic‐predominant, 9% were non‐amnestic, 4% were visuospatial‐predominant, and 5% were language‐predominant.ConclusionApplying a neuropsychological data‐driven method of phenotyping EOAD individuals uncovered a more detailed understanding of the diversity of presenting heterogeneity in this atypical AD group compared to clinical judgment alone. These results suggest that clinicians and patients may over‐prioritize memory dysfunction during subjective reporting at the expense of non‐memory symptoms, which has important implications for diagnostic accuracy and treatment considerations. We plan to investigate the patterns of cortical atrophy and network dysfunction subserving this heterogeneity.
Exploring the validity of two memory markers for Alzheimer’s disease to detect Mild Cognitive Impairments in community‐dwelling older adults from southern Colombia
Authors: Parra‐Rodriguez Mario A , Gonzalez‐Hernandez Alfredis , Bonilla‐Santos Jasmin , Cala Dorian , Gonzalez‐Montealegre Rodrigo A 
Published: January 2025

AbstractBackgroundTraditional neuropsychological assessments have proved insensitive to identify the preclinical stages of Alzheimer’s disease (AD). Such a barrier has proved more challenging when assessing individuals from underrepresented populations (Parra et al., 2018; 2020; 2022). Two memory tests have been proposed as promising to identify people at risk of AD preclinically (Costa et al., 2017; Forno et al., 2022). These are the Visual Short‐Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT). These tests have never been used together to assess individuals from low socioeconomic backgrounds in their communities. This was the aim of this study.MethodWe recruited a sample of 390 volunteers from different community settings in Southern Colombia. After applying the classical clinical criteria, 142 were classified as healthy controls (HC), and 248 received a diagnosis of mild cognitive impairment (MCI). Participants were subjected to a neuropsychological assessment using a standardized battery (Bonilla‐Santos et al., 2023) and the two memory markers for AD (i.e., VSTMBT and FCSRT). We compared groups using their background assessments and these novel memory markers. We also compared the accuracy of these tests to discriminate between cognitively unimpaired older adults and patients with MCI.ResultPatients with MCI were younger [t(388) = 7.2, p <0.001], had fewer years of education [t(388) = 10.42, p <0.001], and, after controlling for age and education, showed the typical amnestic multidomain profile. The VSTMBT revealed a Group by Condition interaction [F(1,388) = 5.60, p = 0.018], whereby MCI patients had significantly larger deficits when processing bound information than individual features. The FCSRT significantly discriminated between patients and controls being free recall the most sensitive variable. None of these outcomes changed after controlling for education, sex, and comorbidities. ROC analysis revealed an AUC of 79% and 72% for the VSTMBT and FCSRT, respectively.ConclusionThe VSTMBT and FCSRT proved sensitive to identifying older people with MCI who had not sought medical advice at the time of testing. These two screening tools are useful for detecting people at risk of AD in community settings of underserved populations.
Cognitive Profile Subgroups Among Non‐demented Older Adults and their Associations with AD Neuroimaging Measures
Authors: Hahn Alice M , Volk Heather E , Albert Marilyn S. , Soldan Anja ,   The BIOCARD Research Team
Published: January 2025

AbstractBackgroundAlthough it is well established that lower cognitive performance, on average, is associated with a greater risk of developing Alzheimer’s disease (AD) dementia, it is unclear whether distinct cognitively‐defined subgroups exist among non‐demented older adults and whether such profiles map onto distinct AD neuroimaging measure profiles.MethodThe sample consisted of 167 non‐demented older adults from the BIOCARD study with comprehensive neuropsychological and clinical evaluations, amyloid PET and brain MRI scans. The MRI measure included: global cortical volume in AD‐signature regions and a medial‐temporal lobe composite; resting‐state functional connectivity within 5 large‐scale cognitive networks; global white matter microstructure, index by fractional anisotropy (FA) and radial diffusion (RD) on DTI scans; and global white matter hyperintensity (WMH) volume on FLAIR scans. A latent profile analysis (LPA) identified cognitively defined subgroups using standardized scores of 8 cognitive tests that cover AD‐related domains (episodic memory, executive functions, working memory, semantic memory, language, visuospatial function, and attention). Multiple linear regression models tested the associations between the group membership and neuroimaging measures adjusting for age, sex, and education.ResultThe LPA identified a model with 3 subgroups as the best solution (AIC = 3515; BIC = ‐3605; ICL = ‐3642; BLRT p = 0.001). The groups primarily differed in terms of performance level: high (36%); average (53%); low (11%). Each group showed distinctive diagnosis composition: high ─ 100% cognitively normal (CN); average ─ 91% CN and 9% mild cognitive impairment (MCI); low ─ 61% CN and 39% MCI. Compared to the high performance group, the low performance group had significantly lower cortical volume in AD vulnerable regions, lower salience/ventral attention network functional connectivity, lower global white matter microstructural integrity, measured by FA and RD, and higher global WMH burden. Amyloid load was not associated with group membership.ConclusionDistinct subgroups defined by cognitive performance exist among non‐demented older adults that are related to AD neuroimaging measures. Evaluating cognitive profiles among non‐demented older individuals may help identify individuals at greatest risk for future cognitive decline.
A Model of Subjective Cognition in Older Adults: Correspondence of cognitive complaints with wellbeing, mood symptoms, and cognitive performance
Authors: Stites Shana D. , Kuz Carolyn , Van Geen Camilla , Scavilla Bob , Kable Joesph , Barber Sarah 
Published: January 2025

AbstractBackgroundBeginning new Alzheimer’s disease (AD) treatments before AD symptoms are prominent would optimize the benefits of these disease slowing treatments. To accomplish this goal, clinicians must identify measures of early disease progression. As a step in doing this, we set out to characterize the relationships between cognitive complaints, wellbeing, cognitive performance, and metacognitive calibration in older adults in order to inform a model of cognition in typical older adults.MethodSample of 344 adults aged 65+ completed an online task. Cognitive complaints were assessed with 7 domains on the Memory Function Questionnaire (MFQ). Wellbeing was measured with ratings of overall wellbeing, health, satisfaction with daily life, anxiety, depression, and Future Time Perspective (FTP) scale. Cognitive performance was captured through reaction times and accuracy on Forward and Backward Digit Span (DS) tasks and accuracy on a Dot Matrix Task (DMT). Participants provided confidence ratings before and after the DMT. Metacognitive calibration (MCC) was operationalized as the difference between trial accuracy reaction time and global post‐DMT confidence ratings. Results reported are statistically significant at P<0.05 unless otherwise stated.ResultsFewer cognitive complains, as indicated by higher reports on all 7 MFQ domains, were associated with better health, wellbeing, and satisfaction with daily life. Most domains (6 of 7) were associated with more expansive FTP, higher anxiety (5 of 7), lower depressive symptoms (7 of 7), higher post‐task confidence (4 of 7), and better MCC (4 of 7). For 89% of participants, confidence ratings either decreased or remained unchanged from before to after the DMT; in the full multivariable model, the group that had confidence increase after the DMT showed lower accuracy (logit = ‐3.71, 95%CI ‐5.80, ‐1.61). In the full multivariable model, the group with low MCC (more confident than quick) demonstrated worse DMT accuracy (logit = ‐1.91, 95%CI ‐3.37, ‐0.45) and worse backward DS performance (logit = 0.25, 95%CI ‐0.04, 0.54, p = 0.09) compared to the typical MCC group (confidence∼reaction time).ConclusionCognitive complaints, wellbeing, cognitive performance, post‐task appraisals of confidence in task accuracy, and the consistency between perceptions and performance (metacognition) are useful constructs for informing a model of subjective cognition in typical older adults.
Acceptability and validity of a smartphone‐administered word list learning test, LILA, in cognitively unimpaired adults
Authors: Lim Yen Ying , Cummins Hannah , Bransby Lisa , Stellman Gabriel , Fredrickson Amy , Edgar Chris J. , Maruff Paul 
Published: January 2025

AbstractBackgroundThe International Shopping List Test (ISLT) is a rater‐administered verbal list learning test, sensitive to memory dysfunction in early Alzheimer’s disease (AD). This study examined the acceptability of a self‐administered ISLT (called LILA) in cognitively unimpaired (CU) middle‐aged and older adults. The validity of LILA was determined by the nature of ISLT learning curves and from examination of the effects of age.MethodCU adults (n = 113) completed LILA on their own smartphone device in a remote, unsupervised setting (n = 113). The LILA app administered a novel ISLT, where a list of 12 shopping list items was read aurally through the speaker to the participant. Participants were required to recall, into the smartphone, as many words as they could remember. This immediate recall trial was repeated three times (T1‐3). After a 10‐minute delay, participants recalled as many of the 12 words as they could. LILA performance measures included, number of words recalled on each trial, and on the delayed recall trial.Result10% of participants (n = 11) failed to provide a response on at least one learning trial (T1 = 3, T2 = 2, T3 = 4, DR = 2), with this data excluded from subsequent analyses. All participants reported feeling highly (74%) or moderately (26%) confident about using a smartphone, and reported using their phone daily. Improvement in immediate recall, known to occur for the ISLT was observed for LILA (Fig 1). Lower LILA immediate recall scores were associated with older age and higher depressive symptomatology (Table 1), but not sex, education or anxiety symptoms. Lower scores on delayed recall was associated with male sex and lower years of education (Table 1), but not age or mood symptoms.ConclusionThe very low rate of data loss indicates high acceptability of LILA in CU middle‐ and older‐aged adults. Validity of performance was indicated by the learning curves, which were qualitatively similar to those of the rater‐administered ISLT, and the effect of age on the immediate recall outcome. These data provide a strong foundation for future studies of the sensitivity of LILA to memory impairment in AD.
Age and Sex Impact Alzheimer’s Disease‐associated Plaques and Tangles in Down Syndrome
Authors: Andrews Elizabeth J. , Phelan Michael J. , Ngo Phong , Rosa Alexis De La , Gonzalez Freddy , Pascual Jesse R. , Wright Sierra , Buckley Rachel F. , Coughlan Gillian T , Kofler Julia , Ikonomovic Milos D , Lai Florence , Ances Beau , Handen Benjamin L , Christian Bradley T. , Mapstone Mark , Head Elizabeth 
Published: January 2025

AbstractBackgroundThe prevalence of Alzheimer’s disease (AD) pathologies in people with Down syndrome (DS) is nearly 100%. In DS, overexpression of APP (on chr21) is associated with increased production of amyloid beta (Aβ) and the formation of phosphorylated tau (ptau) tangles. In the general population, women exhibit higher burdens of ptau compared to age‐matched men with AD. We hypothesized that in DS women would have higher ptau levels compared to men, and that age would significantly correlate with the presence of neuropathology.MethodsWe examined 88 brains (frontal and occipital cortices) of people with DS (age 1‐39yr; M/F = 19/12) and DSAD (age 42‐61yr, M/F = 20/19) and age‐matched controls. Serial sections were immunostained for ptau (AT8) and Aβ (6E10) and quantified using annotated regions of interest from whole slide images in QuPath. Spearman rank correlations of load data were calculated, the Mann‐Whitney U test was used to compare men (n = 20) and women (n = 16) with DS. Mean positivity data was modeled using beta binomial regression in our cohort.ResultsWhen comparing neuropathology loads of DS individuals (age 40+), women show consistently higher median levels of Aβ and ptau. Differences were not statistically significant. Aβ and ptau were both significantly correlated with age in the grey matter of the frontal (Aβ: r = 0.76, p≤0.001; ptau: r = 0.72, p≤0.001) and occipital cortices (Aβ: r = 0.72, p≤0.001; ptau: r = 0.70, p≤0.001). Interestingly, the positive correlation with ptau and age within the occipital cortex appears to be stronger in women (R = 0.80, p≤0.0001) than in men (R = 0.71, p≤0.01). We were able to determine that AD pathology presents in the frontal cortex approximately 10 years earlier than the occipital cortex and increases exponentially after age 40.ConclusionThese results suggest age significantly impacts AD pathology in DS, with neuropathologies presenting in the frontal cortex approximately 10 years earlier than the occipital. Trends indicate sex does appear to have an impact on these pathologies, particularly in the occipital cortex where ptau was found to have a stronger association with age in women. Collectively, this warrants further investigation on the impact of sex and age on AD neuropathology in DS and the contributing mechanisms.
Cerebellar and cerebral contributions to social inference impairments in early stages of Alzheimer’s disease
Authors: Chen Yu , McEachen Bailey A. , Syed Faatimah , Antoniou Rea , Rijpma Myrthe Gwen , Rosen Howard J. , Kramer Joel H. , Miller Bruce L. , Rankin Katherine P. 
Published: January 2025

AbstractBackgroundDespite the prevalent belief that socioemotional processing remains mostly intact in the early stages of Alzheimer’s disease (AD), impaired Theory of Mind – the ability to understand and interpret others’ thoughts, beliefs, and feelings – has been observed in persons with AD. During everyday conversations, the high cognitive loading of socioemotional interactions may adversely impact the ability of persons with AD to identify emotions and read others’ intentions. This study aimed to investigate socioemotional perception capabilities in early‐stage AD and to determine whether cerebellar and cerebral integrity predicts performance on socioemotional perception tests.MethodFifty‐two individuals meeting McKhann criteria for probable AD syndrome and 52 healthy older controls were evaluated with the Awareness of Social Inference Test (TASIT) – Emotional Evaluation Test (EET) and Social Inference‐Enriched (SIE). These tests use videos of conversations to evaluate the ability to identify basic emotions and understand intentions in realistic everyday scenarios. The EET evaluates emotion reading and the SIE examines social inference understanding. We further conducted voxel‐based morphometry with participants’ earliest structural magnetic resonance imaging scans to identify the relationship of cerebellar and cerebral integrity with individual task performance (p<.05 for cerebellar, p<.0005 for cerebral associations, family wise error corrected).ResultsPatients with very early‐stage AD (Global Clinical Dementia Rating = 0.8±0.4) performed worse on both TASIT‐EET and TASIT‐SIE relative to healthy controls (p<.05). Subregions of the cerebellum including bilateral lobules I‐VI, VIIIa, VIIIb, IV, Crus I, II, and the vermis were associated with TASIT‐EET performance. The entire left cerebellar hemisphere, right lobules VI, VIIIa, IX, Crus I, and the vermis were implicated in TASIT‐SIE performance. Cortical subregions in networks involved in memory, semantic comprehension, salience, and socioemotional interpretation were associated with TASIT performance, with TASIT‐SIE more right lateralized.ConclusionThese results clarify that in early‐stage AD, cerebellar involvement and its interaction with corresponding cerebral regions may play a more important role in socioemotional processing than previously appreciated. Specifically, left‐lateralized cerebellar and right‐lateralized cerebral damage predicted poorer social inference understanding in persons with AD. Their emotion reading, in contrast, involved cerebellar and cerebral hemispheres more bilaterally.