bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression and Hippocampal Subfield Volume in Older Adults
Authors: Twisselmann Alicia M , Tennant Victoria R , Hall Brandon J , Liu Joshua D , Hazra Nalini , Wheeler Koral V , Davison Marylan , Matsiyevskiy Elizabeth , Hall James , Borzage Matthew , Johnson Leigh , Yaffe Kristine , Toga Arthur W. , O'Bryant Sid E. , Braskie Meredith N ,   for the HABS‐HD Study Team
Published: December 2023

AbstractBackgroundMajor Depressive Disorder (MDD) is associated with higher risk for developing Alzheimer’s Disease (AD), (Bennett & Thomas, 2014). Both conditions are associated with smaller hippocampal subfield volumes, and both preferentially affect females (Shi et al., 2021). We examined the relationship between depression diagnosis and hippocampal subfield volume, by carrier status for AD genetic risk variant APOE4 and sex. We hypothesized that the association between depression and subfield volume would be stronger in females due to the higher rate of depression.MethodWe examined 1726 cognitively intact older adults from the Health and Aging Brain Study ‐ Health Disparities (HABS‐HD) cohort (Table1) who had available hippocampal high resolution MRI scans (Siemens Skyra or Vida‐3T). Scans were segmented into CA1, CA23DG, and subiculum using Automatic Segmentation of Hippocampal Subfields (ASHS) software and subfield volume was averaged bilaterally. We used separate multiple linear regressions to assess the association between depression and each hippocampal subfield volume, covarying for age, sex, years of education, number of MRI slices segmented, intracranial volume, and scanner. We corrected for multiple comparisons across regions using FDR correction. We also evaluated CA1 and CA23DG volume to depression diagnosis, stratifying by APOE4 positivity and sex and testing for formal interactions.ResultSee Table 2 for results. Depression was associated with smaller CA1 and CA23DG volume across all participants. Depression was associated with smaller CA1 and CA23DG in the APOE4 negative group, but not the APOE4 positive group. The depression by APOE4 interaction was significant for CA23DG volume (𝛽 = 0.25, p = 0.049). Depression was associated with smaller CA1 and CA23DG volumes in males, but not in females, with trend level interaction effects in the CA1 (𝛽 = 0.13, p = 0.095) and CA23DG (𝛽 = 0.17, p = 0.067).ConclusionDepression was associated with smaller CA1 and CA23DG volumes in older adults consistent with past literature. In contrast to our hypotheses, depression was associated with lower hippocampal subregional volumes more in those with lower risk for Alzheimer’s disease (male and APOE4‐ adults).Variability induced by other AD risk factors may mask the relationship between depression and hippocampal subregion volume when AD risk is higher.
Effects of lithium on phosphatidyinositol‐3‐kinase signaling pathways in triple transgenicanimals of Alzheimer’s disease
Authors: Couto Caíque de Oliveira Portugal , Wagner Carlos , Forlenza Orestes Vicente , De‐Paula Vanessa V.J. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), a severe, progressive and multifactorial disease. Among the altered biological pathways, we have the phosphatidyl inositol 3 kinase (PI3K), an important cell signaling mediator that loses its function as a result of changes in the Tau protein and Aβ toxicity. Our aim is to determine the ontological pathways related to PI3K in 3xTg‐AD animals chronically treated with lithium at therapeutic and subtherapeutic doses. Also determine the unique, statistically significant proteins of the biological pathways in the ontological pathway altered in hippocampal tissue.MethodThe animals' hippocampus (WT and 3xTg‐AD) were divided into three subgroups: Li0 (standard chow); Li1 (ration containing 1.0 g of lithium carbonate/Kg); and Li2 (ration containing 2.0 g of lithium carbonate/Kg). Primary cultures of hippocampal neurons were treated with doses of 0.02; 0. 2 and 2mM. The identified protein pathways will be compared by Gene Ontology, using ClueGO, a Cytoscape software plug‐in. The analyzes for comparison with neurons and subsequent tissue identification will be performed by ‘Benjamini & Hochberg False Discovery Rate’ (p≤0.05 setting) for test correction for ‘biological process’. Ethical committee (1293/09).ResultOur results on PI3K showed enrichment of pathways: response to hormone, cell migration, cellular response to endogenous stimulus, positive regulation of response to stimulus and regulation of catalytic activity.ConclusionInitial results are promising for the pharmacological understanding of lithium as a neuroprotector for Alzheimer’s disease.
Cholesterol accumulation promotes ABCA1 degradation in astrocytes via Caveolin‐1 mediated endocytosis in ApoE4
Authors: Wang Shaowei , Li Boyang , Kerman Bilal Ersen , Sun Yi , Bennett David A. A , Arvanitakis Zoe , Remaley Alan T , Yassine Hussein N. 
Published: December 2023

AbstractBackgroundApolipoprotein E4 (ApoE4) dysregulates cholesterol metabolism in the brain promoting the accumulation of lipid droplets, synaptic dysfunction and associates with a greater Alzheimer’s disease risk. We previously demonstrated that ApoE4 reduces the function of ATP‐binding cassette transporters A1 (ABCA1) which has important roles in cholesterol transport. The mechanisms of how ApoE4 induces less ABCA1 activity are poorly understood.MethodABCA1 binding proteins were analyzed with mass spectrum after immunoprecipitation. Immortalized astrocytes, primary astrocytes, mouse brain and human postmortem brain samples were used to test the association of ABCA1 and caveolin‐1 levels. Small interfere RNA was used to knockdown caveolin‐1 expression and 3H labelled cholesterol was used to test the cholesterol efflux of ABCA1.ResultHere, we enriched ABCA1 binding protein complexes from ABCA1‐overexpressing cells treated with recombinant ApoE3 or ApoE4 proteins for a proteomic screen implicating endocytosis as a major pathway differentiating ApoE3 from ApoE4. Among the protein targets discovered, caveolin‐1 expression increased after ApoE4 treatment. Caveolin‐1 and ABCA1 interactions were confirmed using immunoprecipitation experiments. Cholesterol accumulation in astrocytes induced caveolin‐1 expression and promoted ABCA1 degradation. Greater caveolin‐1 and lower ABCA1 expression was observed in brains of 8, 18 and 22 months‐old ApoE4‐TR mice compared with the corresponding ApoE3‐TR mice. Isolation of single cell types from adult mouse ApoE‐TR brains confirmed lower ABCA1 and greater caveolin‐1 expression was largely driven by astrocytes and not microglia or neurons enriched fractions.ConclusionIn conclusion, cholesterol accumulation induced by ApoE4 promotes ABCA1 degradation in astrocytes partly through a caveolin‐1 dependent endocytosis pathway.
Plasma pTau181 and biomarker combinations to identify Alzheimer´s disease at any stage along the AD continuum compared with both controls and non‐AD dementia
Authors: Doecke James D , Bellomo Giovanni , Vermunt Lisa , Alcolea Daniel , Halbgebauer Steffen , in ’t Veld Sjors G.J.G. , Mattsson‐Carlgren Niklas , Veverova Katerina , Fowler Christopher J , Boonkamp Lynn , Koel‐Simmerlink Marleen , Hussainali Zulaiga , Ruiters Daimy N. , Gaetani Lorenzo , Toja Andrea , Fortea Juan , Pijnenburg Yolande A.L. , Lemstra Afina W. , van der Flier Wiesje M. , Hort Jakub , Otto Markus , Hansson Oskar , Parnetti Lucilla , Masters Colin L , Lleó Alberto , del Campo Marta , Teunissen Charlotte E. 
Published: December 2023

AbstractBackgroundThe latest generation of plasma biomarkers (phosphorylated Tau181 (pTau181), Glial fibrillary acidic protein (GFAP), Neurofilament light (NFL) and the Amyloid‐beta ratio (Aβ42/40) have demonstrated high accuracy to detect AD pathology in either CSF/PET by many single‐center studies. Here we assess which markers (alone/combined) can best identify any stage along the AD continuum from a group of controls and other non‐AD dementias in a large international multicentre study.MethodPlasma samples (n = 1298) were collected from six international centers (JPND bPRIDE consortium), including 198 cognitively unimpaired (CU) Aβ‐, 181 CU Aβ+ (preAD), 170 stable mild cognitive impairment (sMCI), 155 MCI due to AD (MCI‐AD), 25 MCI due to Lewy Body Dementia (MCI‐DLB), 46 MCI due to Frontotemporal Dementia (MCI‐FTD), 182 AD dementia, 171 DLB, and 170 FTD. Markers included Aβ40, Aβ42, GFAP, NfL and pTau181 using Simoa. Univariate and multivariate modelling (including their ratio’s and interactions, age, gender and APOE ε4 status) and ROC analyses were performed to assess biomarker capability to separate clinical groups along their disease continuum.ResultpTau181 had the strongest differences between clinical groups (Figure 1) and the best AUC value to separate any AD stage from non‐AD dementia stages and controls (AUC>0.90) for the AD vs CU, sMCI or FTD comparisons. In comparison, the AUC for AD vs DLB was lower (complete sample: AUC:0.77 (95%CI:0.72‐0.82), while the pTau181/Ab42 ratio performed slightly better (p = 0.06, AUC:0.81 (95%CI:0.76‐0.85). Stratifying the AD vs DLB comparison into Aβ‐ and Aβ+ subgroups however, showed substantially increased performance for pTau181 in Aβ‐participants (Aβ‐ AUC: 0.94 [95%CI:0.86‐1.0], Aβ+ AUC: 0.68 [95%CI:0.61‐0.75]) with pTau181 higher in AD participants irrespective of Aβ status. Multivariate modelling showed that a combination of GFAP/Ab42 ratio, Aβ40 and pTau181 and their interaction, and APOEε4 was best to demarcate preAD, MCI‐AD and AD from CU (AUC values 0.89, 0.95 & 0.97 respectively).ConclusionpTau181 performed well to separate the complete AD continuum from controls and FTD but was lower for the AD/DLB comparison prior to stratification for Amyloid status. Multivariate assessment revealed that a combination of markers including pTau181, Aβ and GFAP was the best predictor of any stage of the AD continuum.
Similarities and differences in cognition as a function of sex: A longitudinal study of healthy control participants from the Parkinson Progression Markers Initiative
Authors: Ohlhauser Lisa , MacDonald Stuart , Gawryluk Jodie 
Published: December 2023

AbstractBackgroundAs the global population of older adults continues to rise, there is an urgent need to understand the expected cognitive changes in healthy aging. Despite sex‐based differences in life expectancy and age‐related diseases such as Alzheimer’s disease, limited research has explicitly examined sex differences in aging. The objective of the current study was to answer three primary questions using longitudinal data for sample of healthy adults: 1) How does cognition change over time? 2) What are the sex differences in cognition? and 3) What are the sex differences in rates of cognitive change over time?MethodLongitudinal data from the healthy control group of the Parkinson’s Progression Markers Initiative was used to examine cognitive changes in healthy adult males (n = 125, mean age = 61.61, SD = 10.97) and females (n = 68, mean age = 59.44, SD = 11.56). Participants underwent annual neuropsychological testing for up to five years. A series of 2‐level linear mixed models estimated within‐person change in cognition over time (i.e., level‐1) and between‐group differences in longitudinal change trajectories as predicted by sex (i.e., level 2). Each neuropsychological measure was modeled separately as a single outcome variable, for a total of seven models.ResultStability in neuropsychological scores was seen over five years. At baseline, males scored higher on the Benton Judgement of Line Orientation Test, while females scored higher on the Symbol Digit Modalities Test, the Semantic Fluency Test, and the Hopkins Verbal Learning Test‐Revised. Rates of cognitive change over time did not significantly differ by sex. Higher age and lower education at baseline predicted lower neuropsychological scores.ConclusionStability in cognition was found across five years in a sample healthy control participants from a large multi‐site longitudinal study. Sex differences in cognition were found in several domains, including visuospatial ability, processing speed, verbal fluency, and verbal memory. However, rates of cognitive change over time did not significantly differ by sex. Higher age and lower education were predictive of lower cognitive functioning. Great intraindividual variability in cognitive trajectories was observed. Future research should continue to examine factors that predict individual trajectories of aging in healthy individuals.
Mild Dementia and the FIFA World Cup! A case report
Authors: Hussein Sahar M , Abass Talal , Musa Susan , Shamoun Sereen , Abdelrahman Nadir G 
Published: December 2023

AbstractBackgroundThe use of reminiscence therapy (RT) to prevent abnormal behaviors in patients with moderate dementia has been well‐established. It has many positive effects in the domains of quality of life, cognition, communication and mood. We are presenting a case where RT decreased abnormal behaviors.Method
Case: An 83‐year‐old man with moderate dementia immigrated to the US. He lives with his family who provided care. No alcohol, tobacco use or illicit drug use was reported. The patient was evaluated by a geriatrician. The patient scored 12/30 in Montreal Cognitive Assessment indicating moderate cognitive impairment. Laboratory tests were unremarkable except Vitamin B12 level (slightly low 181). He was started on Donepezil and Vitamin B. Since his arrival to the US, the patient intermittently displayed abnormal behaviors including agitation, sleep disturbance and mood changes. Family members utilized his personal stories, hobbies and interests for behavioral interventions. A soccer‐focused RT method was applied. Several Youtube videos containing old matches during the FIFA World Cup were used whenever abnormal behavior was triggered.ResultFamily reports that the patient’s behaviors were relieved and interestingly improved using the soccer‐focused RT.ConclusionThis case report highlights the importance of a thorough evaluation of patients with dementia to include their life story and interests. In this case, behavioral modalities including RT were tried with considerable benefits. Technology‐based tools present a fertile land to explore regarding RT use in patients with moderate dementia.
References:Bob Woods et al. Reminiscence therapy for dementia. Cochrane Database Syst Rev . 2018 Mar 1;3(3):CD001120. https://doi.org/10.1002/14651858.CD001120.pub3Laura Coll‐Planas et al. Developing Evidence for Football (Soccer) Reminiscence Interventions Within Long‐term Care: A Co‐operative Approach Applied in Scotland and Spain. J Am Med Dir Assoc. 2017 Apr 1;18(4):355‐360. https://doi.org/10.1016/j.jamda.2017.01.013. Epub 2017 Mar 7. PMID: 28283380Teuntje R Elfrink et al. Life story books for people with dementia: a systematic review. Int Psychogeriatr . 2018 Dec;30(12):1797‐1811. https://doi.org/10.1017/S1041610218000376. Epub 2018 Jul 18. https://pubmed.ncbi.nlm.nih.gov/30017005/TikTok Video: #artist #painter #father #daughter #dementia #beauty #life #memories https://www.tiktok.com/@reyssongs/video/7171555440759754027 accessed 1/23/22
Dementia Associated Diseases, Driving Status, and Cognitive Function: Perception Does Not Match Performance – Truth and Consequence for Driving Shared Decision Making
Authors: Kaczmarek Olivia , Weller Joanna , Gopie Ian , Baek Steven , Bumstead Barbara , Buhse Marijean , Zarif Myassar , Gudesblatt Mark 
Published: December 2023

AbstractBackgroundDementia associated diseases (DAD) refer to a group of disorders clinically characterized by progressive cognitive impairment (CI). CI may reflect abnormalities across multiple cognitive domains (CD) to varying degrees and combinations and interfere with the ability to carry out activities of daily living (ADL). Determination of driving ability in routine care relies on patient, family, and clinician shared‐decision making, as availability of routine on‐road driving assessment might be limited. Incorporation of patient reported outcomes (PRO) in routine care has increased, becoming more important for patient care and treatment decisions. Neuro‐QoL Cognitive Function Questionnaire (CF) provides an opportunity to assess self‐reported cognition routinely. The relationship of CF to objective computerized multi‐domain cognitive testing and self‐reported driving has not been explored. Providing easily available objective screening might be of great value for all involved in the decision to continue or stop driving in view of the profound impact loss of driving has on independence.MethodA retrospective review of PwDAD who provided self‐reported driving status and completed both objective and subjective cognitive function (CF) measures. Subjective CF was measured by CF score which pertaining to comprehension, cognition, attention, and learning. The validated computerized cognitive assessment battery (CAB‐NT), includes 7 cognitive domains: memory(Mem), executive function(Exe), attention(Att), information processing speed(Inf), visual‐spatial(Vis), verbal function(Ver), motor skills(Mot) and a global cognitive summary score(GCS). T‐tests and regression analysis was utilized for analysis assuming both equal and unequal variances, with significance (p< 0.05).Results496 PwDAD, average age 73.4±8.9, 61.2% female. T‐test showed significant differences between driving status yes/no for both CF and all CAB‐NT domains. However, regression analysis showed a small effect size between CF and CAB‐NT cognitive domains scores.ConclusionSelf‐reported driving status in PwDAD corresponds to both perceived/subjective CF and objective measures of cognitive function. However, the relationship between subjective and objective cognitive function measures is problematic. With various CDs involved in the safe effective operation of a motor vehicle, it is necessary to objectively assess this risk with objective measures. Evidence of incongruent relationship between objective and subjective cognitive function enhances the importance of incorporating objective measures of cognitive ability to safely maintain an active driving status.
Synaptic tauopathy in a model of Alzheimer’s disease and traumatic brain injury
Authors: Sauerbeck Andrew D , Beck Alyssa , Harman Jacob , Kummer Terrance T 
Published: December 2023

AbstractBackgroundSynapse loss is an early, pathogenic hallmark of Alzheimer’s disease (AD) and related neurodegenerative conditions. We recently demonstrated that traumatic brain injury (TBI) – the best‐established environmental risk factor for AD – also causes synapse loss, thus establishing a potential pathomechanistic connection between these conditions. One likely contributor is the microtubule associated protein tau. Phosphorylated isoforms of tau can be identified in the brain after TBI and are classically associated with AD‐related pathology. The extent to which these pathoisoforms reach synapses and contribute to their loss, however, is minimally explored.MethodWe combined the PS19 mouse model, which exhibits age‐dependent tau aggregation and synapse loss, with early TBI and subsequent aging to investigate tauopathic synaptic alterations in relation to traumatic and AD‐related processes. TBI was induced with a diffuse, closed‐head injury model called modCHIMERA (Sauerbeck et al, 2018) that causes delayed synapse loss. Synaptic analysis was performed with SEQUIN (Sauerbeck et al, 2020, Reitz et al, 2021), a super‐resolution imaging and analysis platform for quantifying synaptic density as well as nanostructure and molecular features in mammalian neuropil.ResultBoth TBI and expression of the P301S mutation resulted in accumulation of pathoisoforms of tau at synapses and regional synapse loss that evolved over time. Temporal and spatial patterns of tau accumulation varied by phosphoisoform. TBI resulted in an additional burden of synapse loss in PS19 animals, suggesting that TBI may increase the risk of AD through a potentiation of synaptic injury. We are exploring the functional consequences of this connection in ongoing experiments.ConclusionThese studies demonstrate novel subcellular targets of pathological tau isoforms and suggest that tau is a key factor in synapse loss in TBI and AD. This shared mechanism may help explain the elevated risk of AD following TBI. Further characterization of these processes may suggest ways to sever this link, as well as prevent synapse loss in primary AD.
Loss of oligodendrocyte‐derived IL‐33 results in increased amyloid plaque deposition in APP/PS1 mice
Authors: Gonzalez‐Fernandez Estibaliz , Szmacinski Alexandra , Mami Salma , Kim Byungwook , Crawley Ilan , Kim Jungsu , Kang Shin 
Published: December 2023

AbstractBackgroundGlial cells in the central nervous system (CNS) express IL‐33, a member of the IL‐1 family. IL‐33 is known to regulate microglial phagocytic activity toward amyloid β. In the aged brain, unlike the young counterpart, IL‐33 is predominantly expressed by oligodendrocytes (OLs), but the role of OL‐derived IL‐33 in Alzheimer’s disease (AD) is unknown.MethodOL‐specific IL‐33 conditional knockout (cKO) mice were further crossed with APPswe/Psen1 dE9 (APP/PS1) and Mobp‐EGFP transgenic mice. Cortical lysates from one‐year‐old male APP/PS1 (n = 15) and APP/PS1 + IL‐33 cKO (n = 16) mice were used for the quantitative analysis (MSD and ELISA) of amyloid β 1‐42 (Aβ1‐42) and Aβ1‐40. Immunofluorescence and morphometric analysis were also performed to measure Aβ‐covered or LAMP1‐covered areas in different regions of the mouse brain. EGFP+ OLs were also quantified.ResultsBoth Aβ1‐42 and Aβ1‐40 levels were significantly increased in the cortex (p<0.0001), and so were Aβ plaque‐covered areas in the cortex, corpus callosum, and hippocampus of APP/PS1 + IL‐33 cKO mice compared with control APP/PS1 (p<0.01). OL‐derived IL‐33 loss also resulted in increased accumulation of LAMP1+ dystrophic neurites (p<0.05). However, cortical EGFP+ OL density was unaltered by IL‐33 cKO.ConclusionOL‐derived IL‐33 may play a regulatory role in Aβ clearance during amyloidogenesis, probably via promoting microglial activity, but not in OL survival in the AD brain. These findings support a novel mechanism of instructive interaction between OLs and microglia in disease‐associated neuroinflammation.