bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression: A risk factor for Dementia?
Authors: Chummar Sydney , Parmar Mayur 
Published: December 2023

AbstractBackgroundDementia refers to impaired cognition, including the ability to remember, think, or make decisions that interfere with everyday activities. The most common types of dementia include Alzheimer’s disease, vascular dementia, and Lewy body dementia. There are various risk factors for dementia, but one factor that needs a more profound understanding is depression. This review study outlines the relationship between depression and the onset, as well as the prognosis of dementia.MethodA literature review (2000‐2022) regarding the impact of depression on the development and progression of dementia was conducted. Eligibility criteria included papers published in peer‐reviewed journals, and studies involving human subjects. Exclusion criteria for this study included systematic reviews and articles published prior to 2000. A computerized search of databases (Google Scholar, PubMed) was performed using keyword search terms such as “depression” AND “dementia.”ResultThe risk of dementia varies with the presence and resolution of depression at different ages. The resolution of depression earlier in life is not associated with an increased risk of dementia, but persistent depression from adulthood to late‐life leads to a greater risk of cognitive decline. Distinct phenotypes of cognitive impairment have been noted in patients with early‐onset vs. late‐onset depression. Late‐life onset depression (LLD) may be an early sign of Alzheimer’s disease, while recurrent depression may contribute to the etiology of vascular dementia. For depression to be a modifiable risk factor, the two treatment modalities studied are: pharmacological and non‐pharmacological. Long‐term treatment of depression with antidepressants like TCAs are associated with a reduced rate in dementia, while treatment with antidepressants like selective serotonin reuptake inhibitors or nonselective serotonin reuptake inhibitors did not reduce the rate of dementia. On the other hand, treatment with exercise training has been shown to improve depressive symptoms.ConclusionLiterature findings suggest that depression has an impact on the development and progression of dementia. Future studies can delve further into whether depression serves as an etiological factor in the development and progression of dementia. The study of such a relationship is important for preventing and treating dementia in the elderly population affected with depression.
Cumulative Frailty in Late‐Middle Aged Men is Associated with Later Regional Abnormal White Matter and Decreased Processing Speed
Authors: Hunt Jack F.V. , Fennema‐Notestine Christine , Buchholz Erik , Lyons Michael J. , Kremen William S. , Franz Carol E 
Published: December 2023

AbstractBackgroundFrailty refers to a person’s physical and functional capabilities and increases during aging. Abnormal white matter (AWM; e.g., hyperintensities on T2‐weighted MRI) is a neuroimaging marker of small‐vessel vascular disease associated with increased risk of Alzheimer’s Disease and related dementias. While some studies have found associations between frailty indices (FIs) and global AWM, their association with accumulation of regional AWM and any related cognitive correlates is understudied.Method342 men from the Vietnam Era Twin Study of Aging with frailty measured at study baseline (mean age = 56.4) and structural MRI scans at follow‐up (mean 5.5 years later) were included (Table 1). The FI measure was based on a cumulative deficit model[1] using an index of 37 health‐ and function‐related items. Global AWM was defined using morphological operators on multi‐channel, three‐class tissue segmentation[2]. A novel watershed routine, applied to our AWM frequency atlas, generated 5 distinct AWM parcellations: frontal, posterior, anterior periventricular, deep, and temporal stem (Figure 1A). Cognitive factor scores (memory, processing speed, executive function, fluency) were derived from normative neuropsychological test performance.ResultMixed‐effects linear regression models controlling for age, years of education and twin‐pair demonstrated that higher baseline FI was associated with greater future AWM volume in temporal stem (p = 0.03) and anterior periventricular (p = 0.02) regions, but not for global or other parcellations (Figure 1B). Baseline FI was not cross‐sectionally associated with any cognitive factor score but was associated longitudinally with decreased processing speed (p = 0.002) (Table 2).ConclusionHigher cumulative frailty in late‐middle aged men was associated with greater future AWM burden and greater decline in processing speed. These findings suggest that cumulative frailty during the 6th decade is a relevant indicator and possible predictor of future pathological structural and functional processes in the brain. Longitudinal studies may elucidate whether frailty affects AWM progression and cognitive decline along a common causal pathway.References:[1] Rockwood K. A global clinical measure of fitness and frailty in elderly people. Canadian Medical Association Journal 2005;173:489‐95.[2] Fennema‐Notestine C, et al. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. NeuroImage: Clinical 2016;12:737‐45.
Long‐term D‐galactose Administration Mimics Natural Aging in Rat’s Hippocampus
Authors: Pantiya Patcharapong , Thonusin Chanisa , Ongnok Benjamin , Chunchai Titikorn , Kongkaew Aphisek , Nawara Wichwara , Arunsak Busarin , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundD‐galactose has been widely used for an induction of premature aging in laboratory animals (1). However, it was observed that short‐term administration of D‐galactose failed to induce some aging phenomena (2). Therefore, we aimed to determine whether long‐term administration of D‐galactose could mimic natural aging of the rat’s hippocampus, based on the primary, antagonistic, and integrative hallmarks of aging.MethodSeven‐week‐old male Wistar rats (n = 12) were randomly injected with either normal saline as vehicle (n = 6) or 150 mg/kg/day of D‐galactose subcutaneously for 28 weeks. Seventeen‐month‐old male Wistar rats (n = 6) were also included as the naturally aged controls. At the end of week 28 of the experiment (when the rats were 35 weeks old for D‐galactose‐induced aging and 24 months old for natural aging), all rats were sacrificed for brain collection. The, the hippocampus was examined for molecular studies.ResultLong‐term D‐galactose administration demonstrated the features of natural aging in the hippocampus of young rats. These include loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication (Figure A). In the context of cognitive function, natural aging and long‐term D‐galactose administration similarly impaired hippocampal learning and memory, as indicated by reducing the novel object location and recognition tests (Figure B, C).ConclusionLong‐term administration of D‐galactose‐induced aging potentially mimic natural aging process of the hippocampus. These findings suggest that long‐term administration of D‐galactose is suitable for an establishment of the aging model in young animals.
Reference
1. Shwe T, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Role of D‐galactose‐induced brain aging and its potential used for therapeutic interventions. Exp Gerontol. 2018;101:13‐36.2. Cardoso A, Magano S, Marrana F, Andrade JP. D‐Galactose High‐Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats. Rejuvenation research. 2015;18(6):497‐507.
Combinations of blood biomarkers in a real‐life memory clinic in Thailand
Authors: Haethaisong Thanaporn , Thanapornsangsuth Poosanu , Booncharoen Kittithatch , Luechaipanit Watayuth , Sarutikriangkri Yuthachai , Tangnimitchoke Suchart , Likitjaroen Yuttachai , Hemachudha Thiravat 
Published: December 2023

AbstractBackgroundDifferent Alzheimer’s disease (AD) blood‐based biomarkers (BBM) exhibit unique patterns and trajectories throughout the natural history of AD, and thus, their combination may result in a higher diagnostic accuracy. While the usefulness of BBM combinations had been demonstrated in research cohorts, their performance in real‐life memory clinics is unclear. Additionally, previous BBM studies have been largely confined to high‐income countries and have often excluded non‐white populations. We aimed to evaluate the performance of BBM combinations in a real‐world clinical setting, specifically in a memory clinic in ThailandMethodThe study enrolled 64 memory clinic patients who had undergone amyloid‐positron emission tomography (PET) or cerebrospinal fluid (CSF) assessment for AD biomarkers. Plasma amyloid‐β42 (Aβ42), Aβ40, p‐tau181 were quantified for each participant using single molecule array as well as APOE genotype determined. The accuracy of individual biomarkers in discriminating amyloid status (as confirmed by PET or CSF) were assessed using receiver operating characteristic (ROC) analysis. Logistic regression models were then created for different BBM combinations, and their performance was determined using ROC analysis. To ensure robustness and generalizability of the results, two‐fold cross‐validation was repeated 10 times on the best‐performing modelResultThe study consisted of 47 (73.4%) female participants with a median age of 70.0 years (interquartile range: 63.75‐75.25). Amyloid status was positive in 43 (67.2%) of the participants. Plasma Aβ42/Aβ40 ratio, Aβ42/p‐tau181 ratio and p‐tau181 had areas under the curve (AUC) of 0.68 (95% confidence interval (CI) 0.52‐0.84), 0.88 (95%CI 0.79‐0.98) and 0.87 (95%CI 0.79‐0.96) for detecting amyloid status, respectively. Logistic regression models that included APOE genotype, Aβ, and p‐tau181 had the highest AUC of 0.90‐0.91. Two‐fold cross‐validation performed on the model that included APOE genotype and the Aβ42/p‐tau181 ratio revealed an average AUC of 0.90 (standard deviation: 0.029) over 10 repeatsConclusionThe combination of APOE genotype, plasma Aβ, and p‐tau181 displayed an exceptionally high diagnostic accuracy in discriminating amyloid status in a memory clinic setting. However, further studies are needed to evaluate the cost‐effectiveness of various ways to implement BBMs into real‐world clinical practice, particularly in low‐ and middle‐income countries
Speech processing in the brain at risk for dementia
Authors: Bolt Elena , Giroud Nathalie 
Published: December 2023

AbstractBackgroundGiven the close relationship between hearing and cognitive function in older age, characterization of speech processing deficits along the auditory pathway is of great importance for the brain at risk of dementia. In the ascending, primary auditory pathway, signals pass through subcortical relay stations in the brainstem and midbrain before being integrated into cortical areas. A recent study suggests that the pathophysiology of MCI extends to speech encoding in the brainstem and that both cortical and subcortical markers of speech processing have predictive potential for putative Mild Cognitive Impairment (MCI). In this project, we are testing these neural speech processing markers to see if they can distinguish healthy older adults with age‐related hearing loss from those at risk for dementia.MethodsElectroencephalography (EEG, 32 channels, sampling rate = 16 384 Hz) will be recorded from N = 40 older participants (age ≥ 60 years, retired) while listening to excerpts from an audiobook. We use a novel EEG paradigm that allows us to simultaneously measure cortical and subcortical responses to natural running speech. Based on their Montreal Cognitive Assessment (MoCA) score, participants are divided into an experimental group with “putative MCI” (MoCA < 26) and a control group (MoCA ≥ 26). In addition, we perform audiometric testing with pure tones (PTA) and speech‐in‐noise (SiN) tests to assess participants' hearing function.ResultsWe are currently in the middle of data collection and will be able to present preliminary results at AAIC. We expect to see altered speech processing in the experimental group, particularly driven by slower and weaker encoding at the subcortical level. In a next step, we aim to use the neural markers of speech processing that emerge from this framework as features for a diagnostic model that predicts MCI using a binary classifier, considering the hearing status of the participants.ConclusionThe main goal of this study is to investigate neural markers of speech processing for their differential diagnostic potential for the brain at risk for dementia. Depending on the results, such neurophysiological markers could prove useful for early diagnosis in the clinic in the longer term.
Cognitive profile of idiopathic normal pressure hydrocephalus (INPH)
Authors: Belessiotis‐Richards Clara , Abrol Esha , Toma Ahmed , Joyce Eileen , Livingston Gill 
Published: December 2023

AbstractBackgroundCognitive deficits in people with idiopathic normal pressure hydrocephalus (INPH) are thought to differ from Alzheimer’s dementia (AD) but this has not been systematically explored.MethodWe undertook a systematic review and meta‐analysis. Peer‐reviewed studies publishing new data, with defined diagnostic criteria for INPH, and using formal cognitive tools were included. Quality was assessed using the Newcastle‐Ottawa Scale. Weighted mean difference (WMD) in score was calculated using random‐effects meta‐analysis for cognitive tests used in at least 2 studies. We assessed heterogeneity using I2. Sensitivity analyses explored results according to global cognition.Result13 studies met inclusion criteria. Participants with INPH had a pooled weighted MMSE score of 22.6 (95% confidence interval (CI) 21.3‐23.9). Studies were divided into those that matched AD participants to INPH participants for global cognition or selected mild AD (n = 6) and those that did not (n = 7). Participants with INPH performed better on the Boston Naming Task across all studies (n = 2; WMD: 1.41; 95% CI: 0.50, 2.31; I2 47%). There were no significant differences in semantic or phonemic fluency, delayed verbal recall, digit span backwards or forwards, or constructional praxis between AD and INPH across all studies. However, sensitivity analyses examining INPH participants compared to mild or matched AD showed significantly worse performance in INPH for semantic (n = 3; WMD: ‐1.37; 95% CI: ‐2.19, ‐0.55; I2 0%) and phonemic fluency (n = 3; WMD: ‐5.18; 95% CI: ‐6.95, ‐3.41; I2 0%), and in the Frontal Assessment Battery (n = 3; WMD: ‐2.33 points; 95% CI: ‐3.30, ‐1.36; I2 0%). Worse performance was also seen on sensitivity analysis in digit span backward (MD: ‐0.70; 95% CI: ‐1.20, ‐0.20) and constructional praxis (MD: ‐0.50; 95% CI: ‐0.90, ‐0.10) but only 1 study was available for each test.ConclusionIn this meta‐analysis, people with INPH tended to score within the mild dementia range on global cognitive testing. There were observable differences in cognitive profile between INPH and AD. People with INPH may have less aphasia but score significantly lower on tests of executive function than people with mild AD. These results could inform identification of INPH in memory services.
Investigating how CSTB affects the activity of cysteine cathepsin in the AD‐DS, EOAD, and human cellular models of trisomy Hsa21
Authors: Wu Yixing , Cleverley Karen , van Dalen Floris , Verdoes Martijn , Crawford Samuel , Wray Selina , Wiseman Frances K 
Published: December 2023

AbstractBackgroundPeople with Down syndrome (DS) have a high genetic risk of developing Alzheimer’s disease (AD) ‐related dementia and pathology. Triplication of a human chromosome 21 (Hsa21)‐located gene APP play an important role in AD pathology. Wiseman et al. demonstrated that triplication of a gene or genes on Hsa21, other than APP exacerbates amyloid‐β pathology in an APP transgenic mouse model. Multiple lines of evidence indicate that cysteine cathepsin activity influences APP cleavage and Aβ accumulation. Cystine cathepsins are predominantly expressed in microglia in the brain and are involved in key neuroinflammation pathways. Hsa21‐located gene CYSTATIN B (CSTB) is an endogenous inhibitor of cathepsin proteases. We hypothesise that three copies of CSTB inhibit cathepsin activity and that this could contribute to altered neuroinflammation in people with DS.MethodHuman fibroblasts from individuals with DS and euploid controls, temporal cortex samples from individuals who had AD‐DS and Braak‐stage matched euploid cases of early‐onset AD (EOAD) or healthy aging and human iPSC‐derived microglia‐like cells (iMLCs: T21 and an isogenic control) were used. Western blot and immunocytochemistry were conducted to determine the abundance and subcellular localisation of CSTB. Cathepsin B (CatB) activity in human fibroblasts and temporal cortex samples was measured using an enzymatic assay (Abcam) and/or a pan‐cysteine cathepsin quenched activity‐based probe (BMV109).ResultWestern blotting confirmed that trisomy of Hsa21 resulted in an increase in the protein level of CSTB, that endogenous CSTB is predominantly localised in the cytoplasm and that its subcellular localisation is not altered by trisomy of Hsa21. Significantly lower CatB activity occurs in the temporal cortex of people who had AD‐DS compared with individuals who had EOAD. However, CatB enzymatic activity was not significantly altered in Hsa21 trisomic fibroblasts.ConclusionNext, we will determine in iMLCs, whether trisomy of chromosome 21 alters CatB activity and which genes have altered expression at baseline and after neuroinflammatory challenge.
The clinical, neuropsychological and neuroimaging characters of GRN mutations carriers in a Chinese PUMCH dementia cohort
Authors: Liu Caiyan , Dong Liling , Wang Jie , Li Jie , Huang Xinying , Lei Dan , Chu Shanshan , Mao Chenhui , Sha Longze , Xu Qi , Peng Bin , Cui Liying , Gao Jing 
Published: December 2023

AbstractBackgroundMutations in the progranulin gene on chromosome 17(GRN) is considered as one of most common causes of frontotemporal lobe degeneration. However, the phenotype and genotype correlation of GRN varies among different cohorts and ethnicities. In Chinese people, the genotype of GRN has not been fully elucidated.Method1945 patients with dementia at Peking Union Medical College Hospital underwent next‐generation sequencing (NGS) analysis. GRN variations classified as likely pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected. The clinical, neuropsychological and neuroimaging characters were investigated.ResultThree patients with four likely pathogenic mutation: p.P50fs & p.W49_P50delinsX, p.P439fs, p.R110X, and thirteen patients with uncertain significance mutations were enrolled. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Asymmetrical atrophy of the frontal lobe and temporal lobe appeared in 64% GRN mutation carriers. Parietal lobe dysfunction or parietal lobe atrophy existed in all patients. White matter lesions existed in 79% patients. The majority of clinical phenotype was frontotemporal lobe degeneration, though cerebral vascular lesions were obvious in some of them especially among old onset patients. The proportion of ApoE e4 carriers were higher in old onset patients than those in young onset ones.Conclusion
GRN mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps.
Social engagement, amyloid burden, and dementia: the Atherosclerosis Risk in Communities (ARIC)‐PET study
Authors: Groechel Renée C. , Liu Chelsea , Knopman David S. , Koton Silvia , Kucharska‐Newton Anna M. , Liu Albert C. , Lutsey Pamela L. , Mosley Thomas H. , Palta Priya , Sharrett Richey , Walker Keenan A. , Wong Dean F. , Gottesman Rebecca F. 
Published: December 2023

AbstractBackgroundAlthough amyloid deposition in the brain is often associated with subsequent dementia risk, not everyone with brain amyloid will develop dementia. This discrepancy illustrates the potential importance that risk factors and lived experiences may have in modifying this association. Compared to participants with low social engagement (SE) in mid‐life, we hypothesized that participants with high mid‐life SE will show a weaker association between amyloid burden and incident dementia.MethodWe included data from 310 non‐demented participants of the Atherosclerosis Risk in Communities (ARIC)‐PET study. Social support and isolation were assessed via interviewer‐administered questionnaires (Visit 2; 1990 – 1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life SE (Table 1). Brain amyloid was evaluated with florbetapir PET (Visit 5; 2011‐2014). Elevated amyloid burden was defined as standardized uptake value ratio (SUVR) >1.2 in the global cortex. Incident dementia cases were identified from visit 5 through 2019 through ongoing surveillance utilizing in‐person neurocognitive testing, informant interviews, and hospitalization codes. Relative contributions of mid‐life SE and elevated florbetapir SUVR to incident dementia, independently and with multiplicative interaction terms, were evaluated with Cox regression models, adjusted for demographics, APOEε4 and vascular risk factorsResultAmong 310 participants, 48 developed dementia (median follow‐up: 4.7 years). Mid‐life SE and elevated SUVR each independently predicted dementia risk but did not interact on a multiplicative scale. Participants with high or intermediate mid‐life SE, relative to low mid‐life SE, were less likely to develop dementia (Table 2). Although the interaction between mid‐life SE and elevated SUVR was not significant, stratified models suggested a stronger association between amyloid burden and dementia in participants with high mid‐life SE (Table 3).ConclusionGreater mid‐life SE was associated with lower odds of developing dementia, independent of elevated SUVR. Although protective, there was no strong evidence for effect modification of mid‐life SE on the association between amyloid and dementia risk. Future longitudinal studies evaluating the potential influence of social factors measured throughout the life course are needed to inform our understanding as to what factors may preserve cognition in the presence of elevated brain pathology.