bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory complaints after COVID‐19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?
Authors: Dong Yiling , Ritto Ana Paula , Damiano Rodolfo Furlan , Coli Amanda Goulart , Hadade Rodrigo , Rocca Cristiana Castanho de Almeida , Serafim Antonio de Pádua , Guedes Bruno Fukelmann , Nitrini Ricardo , Forlenza Orestes Vicente , Filho Geraldo Busatto ,   HCFMUSP COVID‐19 Study Group
Published: January 2025

AbstractCognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post‐acute sequelae of SARS‐CoV‐2 infection. This study aims to investigate subjective memory complaints in COVID‐19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS‐CoV‐2 infection or with symptoms of psychiatric conditions. A total of 608 COVID‐19 survivors were evaluated in‐person 6 to 11 months after hospitalization, with 377 patients assigned to a “no SMC” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow‐up evaluations included an objective cognitive battery and scale‐based assessments of anxiety, depression, and post‐traumatic stress symptoms. We found the perception of memory impairment in COVID‐19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p<0.05); however, the psychiatric symptoms all had large eta‐squared values (ranging from 0.181 to 0.213), whereas the cognitive variables had small/medium eta‐squared values (ranging from 0.002 to 0.024). Additionally, multiple regression analysis indicated that only female sex and depressive and post‐traumatic stress symptoms were found to be predictors of subjective memory complaints. These findings may help guide clinical evaluations for COVID‐19 survivors presenting with memory complaints while also serving to expand our growing understanding of the relationship between COVID‐19, subjective memory complaints, and the risk of cognitive decline.
Racial and Ethnic Differences in Older Adults’ Financial Capacity and Differential Effects of Clinical Factors
Authors: Therrien Sarah , Li Oceanna Yueran , Lin Feng Vankee 
Published: January 2025

AbstractBackgroundFinancial capacity (FC) encompasses one’s ability to understand and complete financial tasks and is essential to older adults’ functional independence. FC is impacted by neuropsychological, neuropsychiatric, and everyday functioning factors in aging. In FC literature, much research does not include demographically representative samples. With a rapidly expanding proportion of older adults from racial and ethnic groups underrepresented in research, it is important to understand factors influencing independence in aging across all segments of the population. Some research shows several FC‐related clinical factors differ between non‐Hispanic white (NHW) and Black/African‐American (BAA) and Hispanic/Latino (HL) groups. Potential differential effects of these factors on groups’ FC are little understood. Here, we aim to understand racial and ethnic differences in FC and how clinical factors affect these relationships.MethodWe used data from ADNI participants with normal cognition, MCI, or AD dementia who completed Financial Capacity Instrument and identified as NHW, BAA, or HL (total n = 900). The Neuropsychiatric Inventory (NPI), Everyday Cognition (ECog) Scale, and Memory and Executive Function (EF) composite scores were used to evaluate clinical factors. Analysis on group differences, main effect of FC, and moderation and mediation analyses were conducted with the clinical stage controlled.ResultBAA (Wald’s 2 = 15.06, p < .001), but not HL, had worse FC than NHW. In the entire sample there were significant correlations between FC and clinical factors (all 2 >7.60 and p<0.006). NPI was a significant moderator with FC in BAA was less impacted by NPI than in NHW (B = ‐0.49, SE = 0.19, Wald’s 2 = 6.84, p = .009). EF (B = ‐0.27, SE = 0.06, 95%CI:‐0.39, ‐0.15) and partner‐report ECog (B = ‐0.05, SE = 0.02, 95%CI: ‐0.09,‐0.01) were significant mediators for FC between BAA and NHW.ConclusionThere are key differences in FC between racial and ethnic groups, especially between BAA and NHW older adults, with neuropsychiatric and neuropsychological factors affecting FC differently between groups.
Associations between Amyloid, Cardiovascular Risk, and Cognitive Function in Korean Older Adults: Insights from the KBASE Cohort
Authors: Chaudhuri Soumilee , Dempsey Desarae A. , Huang Yen‐Ning , Cao Sha , Chumin Evgeny J. , Craft Hannah , Crane Paul K. , Mukherjee Shubhabrata , Choi Seo‐Eun , Lee Michael L. , Scollard Phoebe , Mez Jesse , Trittschuh Emily H. , Klinedinst Brandon S , Nakano Connie , Hohman Timothy J. , Yi Dahyun , Byun Min Soo , Risacher Shannon L. , Nho Kwangsik , Saykin Andrew J. , Lee Dong Young ,   Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE)
Published: January 2025

AbstractBackgroundUnderstanding the relationship between cardiovascular burden, amyloid, and cognition in Alzheimer’s disease (AD) is essential for targeted interventions, especially in ethnically diverse populations where research remains limited. This study aimed to investigate these relationships in a cohort of Korean older adults along the AD spectrum.Method526 participants from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort were included in this study. Vascular burden was quantified using Framingham Risk Score (FRS) and participants were categorized into four groups based on combinations of FRS (FRS High or FRS Low with a median split) and amyloid status (Aβ+ or Aβ‐ based on a cut‐off of 1.2373). Cognitive function was evaluated using standardized neuropsychological tests processed with structural equation models to produce domain scores for memory, executive functioning, language, and visuospatial. ANOVA was employed at baseline to analyze cognitive differences among these groups and within each clinical diagnosis. Longitudinal mixed effects models spanning a period of four years from the initial visit captured cognitive changes over time within these groups (Figure 1).ResultSignificant group and pairwise differences were observed among the four groups in all cognitive domains (p < 0.0001). Stratified analysis within each clinical diagnoses group revealed that CN individuals in FRS high Aβ‐ demonstrated significantly lower memory scores compared to those with FRS low Aβ‐ (p < 0.0001), this trend was absent from MCI and AD groups (Figure 2). Longitudinally, FRS high Aβ+ and FRS low Aβ+ groups consistently demonstrated lower memory scores compared to the FRS low Aβ‐ group. Interestingly, no significant difference in cognition was observed between FRS high Aβ‐ and FRS low Aβ‐ groups over time. However, the most pronounced divergence in longitudinal cognition of the four FRS and Amyloid groups was observed within the MCI diagnosis group (Figure 3).ConclusionThis study highlights the differential impact of cardiovascular risk on cognition depending on amyloid status and clinical diagnosis group. This underscores the importance of considering both cardiovascular risk factors and amyloid pathology early‐on in understanding clinical manifestation and cognitive decline in the AD spectrum, particularly in ethnically diverse populations.
Young Onset Neurocognitive Impairment, Amyloid Positivity, and Psychiatric Symptoms in Underrepresented Populations in the HABS‐HD Cohort
Authors: Culhane Julia E. , Arentoft Alyssa , Guzman Vanessa A. , Cham Heining , Byrd Desiree , Calcetas Amanda T. , Mindt Monica Rivera 
Published: January 2025

AbstractBackgroundAdults from underrepresented populations (URPs), including non‐Latinx NLB (NLB) and Latinx adults, have higher Alzheimer’s disease and related dementia (ADRD) rates than non‐Latinx Whites (NLWs). Young onset dementia is diagnosed when symptom onset occurs before age 65, and little is known about mild cognitive impairment (MCI) and dementia rates in younger URPs. We examined neurocognitive diagnoses, amyloid positivity, and psychiatric symptoms in adults from URPs under 65.MethodsA total of 1,562 participants under 65 (Mage = 57.8, SD = 4.18; Meducation = 13.08, SD = 4.09; Ethnocultural Status: 28.9% NLB, 46.2% Latinx, 24.9% NLW; Gender: 65.5% Female) from the Health and Aging Brain Study‐Health Disparities (HABS‐HD) completed a neuropsychological (NP) battery and received Clinical Dementia Rating Scale (CDR) scores. Study partners completed the Physician’s Estimate of Duration for AD‐related psychiatric symptoms (e.g., mood changes, anxiety/nervousness). Diagnoses (i.e., cognitively unimpaired (CU), MCI, dementia) were conferred using HABS‐HD consensus diagnosis criteria. A subset of 756 participants (M = 57.4, SD = 4.21; 57.7% NLB, 27.6% Latinx) underwent PET imaging with Florbetaben (FBB); amyloid positivity was defined by an SUVR of 1.08. Chi‐square tests were computed to examine associations across ethnocultural groups (i.e., NLB, Latinx, and NLW) and neurocognitive diagnoses, amyloid positivity, and psychiatric symptoms.ResultsThe NLB group had significantly higher rates of MCI and lower rates of CU based on consensus diagnoses (n = 451; MCI = 30.6%, CU = 63.2%), compared to NLW (n = 389; MCI = 14.1%; CU = 80.7%, X2
= 41.20, p<.001) and Latinx groups (n = 722; MCI = 18.6%; CU = 76.2%, X2
= 40.09, p<.001). The NLB group also had higher rates of psychiatric symptoms, including mood changes (X2
= 17.70, p<.001), anxiety/nervousness (X2
= 13.05, p = .001), and aggression/irritability (X2
= 15.29, p<.001) compared to NLW and Latinx groups. In contrast, amyloid positivity and dementia rates did not significantly differ across groups (all ps>.05).ConclusionYoung NLB participants in HABS‐HD had increased rates of MCI and psychiatric symptoms compared to NLW and Latinx participants. Also notable, there were no significant ethnocultural differences in amyloid positivity or dementia diagnosis. These patterns differ from those previously documented in primarily NLW samples, suggesting that psychosocial and possibly sociocultural factors may differentially affect cognitive health outcomes among middle‐aged NLB adults. Future research, with deeper sociocultural phenotyping, may help elucidate the potential mechanisms driving these differences.
A pilot study evaluating the feasibility, safety, and efficacy of transcranial photobiomodulation (tPBM) for the treatment of mild cognitive impairment (MCI): preliminary findings
Authors: Rashidi‐Ranjbar Neda , Churchill Nathan W. , Graham Simon J. , Schneider Raphael , Rajji Tarek K. , Andreazza Ana C. , Lim Lew , Coull Jeff , Munoz David G. , Fornazzari Luis R , Schweizer Tom A. , Fischer Corinne E. 
Published: January 2025

AbstractBackgroundMild Cognitive Impairment (MCI) is often a precursor to Alzheimer’s dementia (AD). Recent research underscores the relationship between mitochondrial dysfunction and amyloid‐beta accumulation, raising the prospect of targeting mitochondrial function for intervention. Transcranial photobiomodulation (tPBM), a non‐invasive technique utilizing near‐infrared light, has been shown to enhance mitochondrial function. Therefore, our study aimed to investigate the efficacy of tPBM in improving brain functions in MCI.MethodsFourteen (N = 14) participants with MCI recruited at St. Michael’s Hospital Memory Disorders Clinic were randomized (1:1) to either active or sham tPBM (Neuro RX Gamma, Vielight Inc). Participants underwent daily home‐based active or sham tPBM sessions over 6 weeks. Pre‐ and post‐treatment assessments included a comprehensive battery of tests, encompassing the Trail Making Test (TMT B & A), Mini‐Mental State Examination (MMSE), Proton Magnetic Resonance Spectroscopy (H‐MRS) of the posterior cingulate cortex, structural MRI, resting‐state functional MRI (rsfMRI), and blood‐based biomarker was collected using NMR spectroscopy quantitative and Neurology 3‐Plex A (N3PA) Assays.ResultsComparing pre‐post changes in the active vs. sham group, we found significant differences favoring the active group (p’s<0.05) in: completing TMT‐B (t‐statistic = ‐2.1); for H‐MRS, decline in N‐acetyl aspartate to total creatine ratio (NAA/Cr) (t‐statistic = 2.8); increase in right thalamic volume (t‐statistic = 3.2); for rsfMRI, higher absolute change in functional connectivity in the default mode network (DMN) (t‐statistic = 3.5) and limbic network (t‐ statistic = 3.3), and between DMN and executive control network (ECN) (t‐statistic = 2.8); for blood results, decrease in isoleucine (t‐statistic = 3.0), methionine (t‐statistic = 3.1), and sarcosine (t‐statistic = 3.2) levels—markers linked to AD and amyloid plaque formation; and increase in butyrate (t‐statistic = ‐2.5) and L‐carnitine (t‐statistic = ‐2.6) levels—markers indicative of improved mitochondrial function. Furthermore, a notable trend was observed towards improved TMT B/A (p = 0.05, t‐statistic = ‐2.2) and MMSE (p = 0.06, t‐statistic = 2.0). Although the reduction in plasma tau levels within the active group was not statistically significant, it was notable (t‐statistic = 1.8).ConclusionsOur pilot study suggests that tPBM could improve executive function, neuronal health, functional connectivity, and mitochondrial function, and decrease AD markers in patients with MCI. Further research with larger sample sizes is essential to replicate and validate these results.
Impact of beta‐amyloid oligomers on in vivo brain glucose metabolism
Authors: da Rocha Andreia Silva , Fontana Igor C. , Peixoto Guilherme G. Schu , Souza Amanda S , Venturin Gianina Teribele , Greggio Samuel , Forny‐Germano Leticia , Lourenco Mychael V , Rosa‐Neto Pedro , Souza Diogo O. , da Costa Jaderson Costa , Ferreira Sergio T , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundThe deposition of β‐amyloid (Aβ) plaques is a classical neuropathological feature of Alzheimer’s disease (AD). Currently, it is believed that intermediate products of the Aβ fibrillogenesis process, like the β‐amyloid oligomers (AβOs), are the most toxic forms, and are involved in neurodegenerative processes in AD. The evaluation of cerebral glucose metabolism in patients with β‐amyloid plaque deposition using [18F]FDG‐PET has been used as a marker of neurodegeneration in AD. However, little is understood about AβOs' impact on glucose metabolism prior to Aβ plaques formation. The aim of this study was to evaluate the impact of the intracerebroventricular infusion of AβOs on in vivo glucose metabolism via [18F]FDG‐PET.MethodMale Swiss mice (3‐month‐old, n = 20 per group) were divided into three groups: Vehicle, AβOs 10pmol, and AβOs 100pmol. Vehicle/AβOs were infused into mice’ right ventricle using the freehand technique after brief isoflurane anesthesia. [18F]FDG‐PET scans were performed 24h after AβOs infusion. The same animals underwent the Novel Object Recognition (NOR) task 24h after scanning. The images were processed and analyzed using MINC tools. Metabolic networks were built by computing Pearson correlation coefficients based on 2,000 bootstrap samples and FDR corrected (P<0.05). See Fig. 1a, for a experimental design illustration.ResultsAβOs induced dose‐dependent brain glucose hypometabolism (Fig. 1b) and metabolic network disturbances. Voxel‐wise percentage change analysis revealed moderate reductions in glucose brain metabolism (5% to 15%) following infusion of 10pmol AβOs, whereas 100 pmol AβOs led to widespread and substantial reductions of up to 25% (Fig. 1c). T‐statistical voxel‐wise analysis indicated statistically significant brain glucose hypometabolism only in the 100pmol group (Fig. 1d). The low‐dose AβOs (10pmol) induced brain inter‐region metabolic hyperconnectivity, while the 100 pmol dose caused hypoconnectivity (Fig. 1e). Furthermore, both AβOs infusion groups exhibited impaired recognition memory in the NOR task (Fig. 1f).ConclusionOur results are the first demonstration of AβOs causing in vivo glucose hypometabolism and metabolic network disturbances in the absence of plaques. These findings point to an early impact of AβOs on glucose metabolism, independent of β‐amyloid plaque formation. While the molecular pathways underlying this effect require further investigation, they may represent important AD pathophysiological mechanisms and potential targets for therapeutic intervention.
Prognostic Significance of Visit‐to‐visit Blood Pressure Variability for Cognitive Outcomes, Vascular Events, and All‐Cause Mortality in a Memory‐Clinic Cohort
Authors: Cui Jiangbo , Hilal Saima , Chen Christopher 
Published: January 2025

AbstractBackgroundThe clinical relevance of visit‐to‐visit blood pressure variability (BPV) remains unclear in the memory‐clinic setting. We aimed to investigate the prognostic significance of BPV for cognitive outcomes, vascular events, and all‐cause mortality in a memory‐clinic population.MethodThe study included 590 participants from an ongoing longitudinal memory clinic study who had ≥ 3 annual visits and a baseline MRI scan. Cognitive decline was defined as an annual increase of 0.5, 1, and 2 in the Clinical Dementia Rating sum of boxes for participants with No Cognitive impairment (NCI), Cognitive Impairment No Dementia (CIND), and dementia, respectively. Incident dementia was identified as transition from NCI or CIND to dementia. Incident vascular event was characterized as occurrence of cardiovascular disease, transient ischemic attack, or stroke. Significant cerebrovascular disease (sCeVD) was defined by MRI visual grading, and medial temporal lobe atrophy score ≥2 indicated neurodegeneration. Time‐dependent joint models were used, adjusting for mean BP, sCeVD, neurodegeneration, and other confounding factors, and accounting for mortality as a competing risk when necessary.ResultOver a mean (SD) follow‐up of 3.28 (1.12) years after the second BP measurement, 294 cases of cognitive decline, 75 cases of incident dementia, 34 vascular events, and 59 cases of all‐cause mortality were recorded. Per 1‐SD increase in systolic BPV (SBPV) is associated with a higher risk of cognitive decline (HR: 1.03, 95% CI: 1.00 to 1.05, p = 0.021) and a higher risk of dementia (HR: 1.09, 95% CI: 1.02 to 1.15, p = 0.002). Subgroup analyses showed that association of SBPV with cognitive decline was significant in dementia‐free participants but non‐significant in those with dementia. These associations remained significant after adjusting for sCeVD and neurodegeneration. Increased SBPV was also associated with all‐cause mortality (HR: 1.08, 95% CI: 1.03 to 1.13, p = 0.006), but not with vascular events. Similar findings were observed with diastolic BPV.ConclusionIncreased visit‐to‐visit BPV was associated with cognitive decline independent of mean BP, sCeVD and neurodegeneration among non‐demented older adults. Our findings suggest BPV may be a modifiable risk factor for adverse events and provide prognostic insights beyond mean BP in memory clinics.
Neurofibrillary tangle characterization in the olfactory bulb among clinicopathologic subtypes of Alzheimer’s disease
Authors: Chalk Jessica L , Kwan Rain , Martin Nicholas B , Moloney Christina M. , Boon Baayla D.C. , Dunlop Sara R , Rothberg Darren M. , Wood Ashley C. , Tranovich Jessica F. , Duara Ranjan , Graff‐Radford Neill R , Dickson Dennis W. , Murray Melissa E. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is neuropathologically heterogeneous and can be objectively classified along a spectrum of corticolimbic tangle distribution as hippocampal sparing (HpSp) AD, typical AD, and limbic predominant AD. The olfactory bulb is an early area of tau accumulation with a direct connection to the amygdala. Although tau pathology has been identified in the olfactory bulb, its association with AD subtypes remains unclear. To investigate these differences, tau markers were characterized within the olfactory bulb among AD subtypes.MethodThe cohort included 39 AD cases (HpSp AD: n = 15, typical AD: n = 12, limbic AD: n = 12). Immunofluorescence staining was conducted on 5 µm thick formalin‐fixed paraffin‐embedded olfactory bulb sections using phosphorylated tau (AT8 & PHF‐1) and C‐terminal tau (2E9) antibodies. Slides were digitally scanned on the PhenoImager™ HT slide scanner and analyzed using QuPath Digital Analysis software, quantifying tau burden as a percentage of positive staining.ResultIn whole olfactory bulbs, AT8 was observed as intrasomal tangle‐like immunoreactivity with some extrasomal neuritic staining. AT8 burden did not differ among subtypes (HpSp AD median = 0.28% [interquartile range 0.014‐1.7%], typical AD = 0.28% [0.027‐2.24%], limbic AD = 0.39% [interquartile range 0.39‐0.74%]). PHF‐1 was observed as intrasomal tangle‐like immunoreactivity with abundant extrasomal neuritic pathology. PHF‐1 was observed to be highest in limbic AD (HpSp AD = 3.5% [0.63‐11%)], typical AD = 3.2% [0.38‐13%], and limbic AD = 5.3% [1.97‐10%]) and differed from typical AD (p<0.05). 2E9 was observed as intrasomal tangle‐like immunoreactivity with minimal extrasomal staining and not found to differ among subtypes (HpSp AD = 0.18% [0.036‐2.2%], typical AD = 0.15% [0.021‐2.4%], and limbic AD = 0.29% [0.0030‐8.2%]).ConclusionAbundant tau accumulation was observed among all AD subtypes with some suggestion of higher tau burden in limbic predominant AD. Given the direct connection between olfactory bulb and amygdala, it is interesting to speculate of an environmental contribution to limbic predominant AD through olfactory bulb damage. Future studies will expand the cohort to include AD cases with Lewy body disease co‐pathology and primary tauopathies with a focus on the anterior olfactory nucleus as the primary site of tau pathology.