bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between memory strategies performance and CSF biomarkers: A new approach for the early intervention in MCI
Authors: Chino Brenda N , Torres Lucia , Żelwetro Agnieszka , Rojo Inmaculada Concepción Rodríguez , Carnes Anna , Piñol‐Ripoll Gerard , Yubero Raquel , Paul Nuria , Maestú Fernando 
Published: June 2023

AbstractBackgroundDiagnostic research criteria for Alzheimer’s Disease (AD) recommend the cerebrospinal fluid (CSF) as a sensible and validated biomarker to improve the accuracy of the prognosis regarding progression to dementia for people with mild cognitive impairment (MCI). Also, it has been established that episodic memory failure is a proxy for AD, while executive functions impairment could be leading to other types of dementia. One of the tests designed to simultaneously evaluate these cognitive functions with high sensitivity and specificity to discriminate between neurocognitive disorders is the Test of Memory Strategies (TMS). The main goals of the present study were 1) to assess the correlations between TMS and CSF markers (i.e., Aβ42, t‐tau, and p‐tau) in a sample of MCI patients, and 2) to provide additional validation for TMS as a clinical tool for Alzheimer’s Disease (AD) early detection.Method135 participants were recruited from a multicenter international study in Poland and Spain, but only 47 were selected (Mean age: 68.58 ± 10.03). The sample was split according to the Erlangen Score Diagnostic Algorithm (ESA) into: CSF ‐ (n = 11) and CSF + (n = 36). Correlations analyses between the five TMS word‐list conditions and CSF biomarkers were conducted, and analysis of covariance (ANCOVA) was performed to define the effect on ESA classification in the sample, using the site of origin of the participants as covariable.ResultsSignificant associations between the TMS‐3 condition and Aβ42, t‐tau, and p‐tau were observed for the whole sample. Also, the CSF‐ obtained a higher cognitive performance in the TMS‐3 than the possible AD group (CSF+).ConclusionsOur results revealed that combining CSF biomarker measures and TMS scores could contribute to a better characterization and a more precise approach to AD. Furthermore, considering that the TMS‐3 condition is mostly associated with executive functions, future interventions should focus on this cognitive construct and how it could affect the patient’s ability to encode and organize the information in memory.
The role of anemia and haemoglobin concentration on cognitive function in the Longitudinal Ageing Study of India‐Diagnostic Assessment of Dementia (LASI‐DAD)
Authors: Winchester Laura M , Newby Danielle , Bauermeister Sarah , Ranson Janice M , Chien Sandy , Hu Peifeng , Llewellyn David J , Lee Jinkook , Nevado‐Holgado Alejo J 
Published: June 2023

AbstractBackgroundAnemia is a condition characterised by low haemoglobin concentration, which is common in elderly populations. In India, anemia is widely researched in childhood development and women of reproductive age, although studies in older populations are lacking. The Longitudinal Ageing Study India ‐ Diagnosis of Dementia (LASI‐DAD) dataset is an ideal cohort to better understand the potential impact of anaemia and changes in blood haemoglobin and cognition in an elderly dataset.Method2,758 respondents from the LASI‐DAD cohort, aged 60 or older, had venous blood samples taken for complete blood count and harmonised cognitive function tests. Haemoglobin concentration was used as the exposure in the linear regression models. Cognition data from in‐depth cognitive tests and informant interviews used the Harmonized Cognitive Assessment Protocol (HCAP). A summary value for each of the 11 tests was used as the outcome. We corrected for age and gender in the basic model with the full model also containing adjustments for rural location, smoking and BMI.ResultCases of anemia are more common in older and rural participants in the Indian population. We found a positive association between haemoglobin concentration and all the harmonised cognitive test measures except the visuospatial measures (b = 0.038 ‐ 0.072 p < 0.05). The strongest association was identified for memory‐based measures (immediate episodic, delayed episodic and recognition, b = 0.045 ‐ 0.072 p < 0.05). This was supported by an association between the general cognitive score and the other red blood count tests including the derived measure mean corpuscular haemoglobin concentration (b = 0.06 p = 0.0001) and Red Cell Distribution Width (b = ‐0.11 p < 0.0001).ConclusionWe have established for the first time in a large South Asian population that anaemia may be an important potentially modifiable risk factor for low cognitive function. As the LASI‐DAD cohort expands to include new timepoints it will be possible to run longitudinal analysis to examine the causal relationship between these measures.
The gut microbe‐derived methylamine TMAO protects against neuroinflammation through restraint of pro‐inflammatory glial behaviour
Authors: McArthur Simon 
Published: June 2023

AbstractBackgroundWhile the ultimate cause(s) for Alzheimer’s disease (AD) are unknown, factors that can modify the risk of its development are clearer. Consumption of a seafood‐rich diet has repeatedly been shown to protect against AD. What is less clear however, is why. Much attention has focussed on omega‐3 fatty acids given their anti‐inflammatory effects in vitro, but translation to human studies have been disappointing. Omega‐3 fatty acids are not the only bioactive components in seafood however. In particular, we have recently shown the dietary methylamine trimethylamine N‐oxide (TMAO), produced by gut microbial metabolism of seafood‐enriched choline, to enhance blood‐brain barrier integrity, prevents glial activation and protect cognitive function following peripheral inflammatory challenge.MethodsWe investigated whether protective effects of TMAO treatment could be extended to neuroinflammatory challenge. Male C57Bl/6 (n = 6) were pre‐treated for 4 weeks with or without TMAO through the drinking water (0.5g/l) prior to unilateral i.c.v. injection of 4 mg/kg streptozotocin (STZ) or saline vehicle. Two weeks post‐lesioning (continuing TMAO treatment as appropriate) animals were killed and assessment was made of hippocampal inflammation. In parallel, the molecular mechanism of action of TMAO was investigated in vitro using immortalised and primary murine microglia, challenged with oligomeric β‐amyloid (100nM).ResultsAnimals treated with STZ showed significant increases in both microglial and astrocytic density in both the CA1 and dentate gyrus regions of the hippocampus, two weeks post‐lesioning, effects that were almost completely attenuated by TMAO pre‐treatment. Study of oxidative and inflammatory markers is ongoing. In vitro analyses of immortalised and primary microglia showed TMAO pre‐treatment (20 µM, 24 h) to prevent lipopolysaccharide (10 ng/ml) or oligomeric β‐amyloid (100nM)‐induced secretion of TNFα, nitric oxide and reactive oxygen species.ConclusionTogether, these data further highlight the importance of TMAO in the gut‐brain axis, and emphasise gut microbial metabolism as a conduit for dietary effects upon the brain. Given that TMAO is ultimately derived from dietary choline, these changes may help explain the well‐known beneficial effects of consumption of a seafood‐rich diet upon dementia risk.
Analysis of amyloid deposits in the retina and implications for use as a biomarker of Alzheimer’s Disease
Authors: Campbell Melanie CW , Mason Erik L , Emptage Laura , Wang Jiyuan , Hamel Michael T , Redekop Rachel , Kitor Monika , Strazzeri Jennifer , Brooks Melissa , Araujo Joseph A , Ran Chongzhao , Hsiung Ging‐Yuek Robin , Mackenzie Ian R , Hirsch‐Reinshagen Veronica , Hunter Jennifer J 
Published: June 2023

AbstractBackgroundIn humans and the naturally occurring canine model of Alzheimer’s disease (AD), we and others observe amyloid deposits in the retina en face. We have previously shown that detecting the number of amyloid deposits with polarised light, using wide field, dye free retinal imaging, can predict the degree of severity of AD pathology in the brain. But some who take thin, transverse retinal sections find amyloid while others do not. Here, we report the surface area of retinal amyloid deposits in human and the canine model of AD.MethodFormalin‐fixed retinas from 29 individuals with a moderate to high likelihood of AD (with some comorbidities excluded) and 20 canines were flat‐mounted and imaged in florescence and polarized light (Fig 1). The full retina was imaged for 24 human and 16 canine retinas. For 4 canines, in‐vivo blue light fluorescent retinal images were collected before and after injection of an amyloid dye, CRANAD‐28. Deposits visible only after injection were counted. Fluorescence and polarization images were compared post‐mortem in a canine after an injection of CRANAD‐28. Amyloid deposits were segmented using custom methods. The total area of segmented deposits was then divided by the total retinal area imaged.ResultIn retinas from individuals with AD brain pathology, the area of the retinal covered by amyloid deposits was on average 0.01% and correlated with the number of deposits (Fig 2). In vivo (Fig 3), the area of the canine retina covered by amyloid deposits was on average 0.29% (Fig 4). In one ex vivo retina, fluorescent and polarization positive deposits had a concurrence of 93% and the average area of fluorescent deposits (0.14%) was larger than the same deposits imaged in polarimetry (0.08%) (Fig. 5).ConclusionThese findings and our previous report of an almost constant density of amyloid deposits across the retina, should guide in vivo imaging of amyloid in the retina as a biomarker of AD. Across all human and canine retinas, amyloid deposits covered less than 0.6% of the retinal surface. Careful, extensive sampling is needed. The surface area of amyloid deposits is an additional potential biomarker of disease severity.
Association of psychological stress and memory decline in US adults
Authors: Reddy Ananya , Zhang Yutong , Alonso Alvaro , Kulshreshtha Ambar 
Published: June 2023

AbstractBackgroundPsychological stress can have long‐term health consequences and has been linked to many chronic conditions. Recent evidence suggests that psychological stress and poor mental health may have long‐term effects on cognition. We aimed to assess the association between psychological stress and memory decline in a nationally representative sample.MethodWe assessed data on participants aged 45 years from the 2020 wave of the Behavioral Risk Factor Surveillance System (BRFSS). BRFSS is a survey of health behaviors and conditions that is administered by telephone across the US. Participants self‐reported memory decline over the past year and days of psychological stress in the past month (categorized as <15 – low, or ≥15 – high), in addition to several sociodemographic factors. The association between memory decline and psychological stress was assessed by multivariate logistic regression, adjusting for age, sex, income, lifestyle and cardiovascular risk factors. Education and race were assessed as effect modifiers.ResultOf 48,460 participants (53.9% female, 82.7% White), 4,132 (8.5%) reported memory decline over the past year. Among those with high psychological stress, 1,248 (25.1%) reported memory decline, compared to 2,884 (6.6%) among participants with low stress (p<0.001). In our crude model, high psychological stress was significantly associated with memory decline (OR = 4.72, 95% CI: 4.39, 5.09). This association persisted after adjusting for demographic, lifestyle and cardiovascular risk factors (OR = 4.18, 95% CI: 3.87, 4.52). There was significant interaction by education and race such that the association between psychological stress and memory decline was stronger in non‐whites with less education (OR = 6.56, 95% CI: 5.39, 7.99) and weaker in more educated whites (OR = 3.62, 95% CI: 3.23, 4.01).ConclusionIn this analysis of a nationally representative sample, psychological stress was significantly associated with memory decline. This association was modified by education level and race, with larger effect sizes among those who were non‐white or had less education. Since psychological stress is a modifiable risk factor, these findings suggest that access to mental health resources and stress reduction efforts may be instrumental in preventing cognitive decline. Further studies are needed to elucidate the role of psychological stress in cognitive decline.
Updated APOE and TOMM40 rs2075650 genotype effects on cognition: a UK Biobank study
Authors: Pollpeter Amy , Klinedinst Brandon S , Larsen Brittany A , Li Tianqi , Wang Qian , Barnett Neil , Moody Shannin , Pappas Colleen , Willette Sara A , Parvin Mohammadiarvejeh , Jonathan Mochel , Allenspach‐Jorn Karin , Willette Auriel A 
Published: June 2023

AbstractBackground58‐79% of late‐onset Alzheimer’s disease (AD) is due to genetic heritability. The epsilon 4 (ε4) variant of Apolipoprotein E (APOE) is the strongest genetic risk factor for AD, yet only accounts for 20% of AD heritability. In addition, the APOE ε2 or ε3 variants appear to have either a protective or neutral effect on AD risk respectively. Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is next to APOE and may modulate different APOE variant effects, such as with the Single Nucleotide Polymorphism (SNP) at rs2075650. Thus, we explored main and interaction effects of TOMM40 and APOE on longitudinal measures of executive function and memory.Method10,347 adults (40‐70y) in the UK Biobank were genotyped for APOE and TOMM40 ‘650. Executive function and memory were tested at baseline and twice over a period of 6‐10 years. Main effects within APOE haplotypes and TOMM40 SNP genotypes (A,G) were analyzed, as well as interactions between these genetic markers.ResultHaving the TOMM40 ‘650 G risk variant was related to better baseline cognitive scores regardless of APOE haplotype (ps <.05), but a greater decline over time in APOE4 carriers (ps <.05) The effects of the APOE haplotype were strongly modulated by sex. Men vs. women had less protective or more detrimental effects based on APOE2 or APOE4 haplotype respectively.ConclusionThe data suggests that TOMM40 modulates APOE, regardless of its haplotype. Future studies should stratify APOE by haplotype to re‐test our findings. In addition, more research needs to be done on the effect of having what we term a “mixed” APOE haplotype (carrying a copy of both the protective and risk gene variants).
Enlarged perivascular spaces are associated with white matter injury and cognition in an autosomal dominant vascular neurodegenerative disease (CADASIL)
Authors: Oh Bradley C , Wang Earnest Y , Tsuei Torie , Cobigo Yann , Baida Maria , Tabdili Yasmine , Park Ryan , Kramer Joel H. , Miller Bruce L , Rosen Howard J. , Elahi Fanny M 
Published: June 2023

AbstractBackgroundEnlarged perivascular spaces (EPVS), quantified on brain imaging, can reflect structural changes of blood vessels or of the surrounding fluid filled spaces. EPVS measures are emerging as promising biomarkers of cerebral small vessel disease, especially in dementia research. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a vascular neurodegenerative disease (VNDD) caused by mutations in the NOTCH3 gene. CADASIL involves disease of small vessels and presents with headaches, early onset strokes, and progressive neuropsychiatric dysfunction. We asked whether “burden” of EPVS is associated with clinical outcomes in CADASIL.MethodBrain MRIs were obtained in a CADASIL cohort (n = 27) and age/sex matched controls (n = 27). EPVS and WMH (white matter hyperintensity, measure of injury) were quantified with a semi‐ automated pipeline, using T1/T2 and FLAIR images, respectively. Participants underwent clinical and neuropsychological tests measuring executive function. Linear regression models were built to test associations between EPVS with WMH (a classical biomarker in CADASIL) and executive function. All models were adjusted for age and sex.ResultWe found no group differences in total EPVS volumes between CADASIL and the control group (β = 0.04, p = 0.73). Age was significantly associated with EPVS only in the control group (β = 0.018, p < 0.05). We found a significant inverse association of EPVS with executive function in CADASIL (β = ‐0.11, p < 0.05) and a positive association of EPVS with WMH (β = 0.28, p = 0.05).ConclusionCADASIL, a vasculo‐centric neurodegenerative disease includes prominent SVD pathology that may be driving total EPVS volumes. This may represent an accelerated vascular aging phenotype. Associations with cognition and MRI measure of white matter injury (WMH) in CADASIL confirm that EPVS may be a relevant biomarker to track in CADASIL. Longitudinal studies will be of great value in determining the utility of EPVS as a disease‐relevant biomarker in future therapeutic trials in CADASIL.
Late life onset of persistent psychosis and incident dementia: risk stratification by baseline cognitive status
Authors: Munir Amlish , Ghahremani Maryam , Smith Eric E. , Creese Byron , Fischer Corinne E. , Ismail Zahinoor 
Published: June 2023

AbstractBackgroundMild Behavioral Impairment (MBI) is a validated neurobehavioral syndrome characterized by later life emergent and persistent neuropsychiatric symptoms (NPS) as an at‐risk state for incident cognitive decline and dementia. Psychosis is one of the five domains of MBI, although dementia risk with MBI‐psychosis is not well quantified. Here, we assessed the longitudinal association of MBI‐psychosis with incident dementia in dementia‐free participants.MethodData were obtained from the National Alzheimer Coordinating Centre (NACC). Participants with neurodevelopmental, neurological and/or psychiatric disorders were excluded. Participants with normal cognition (NC) or mild cognitive impairment (MCI) at baseline were included. MBI‐psychosis status was defined based on persistence of Neuropsychiatric Inventory Questionnaire delusions and hallucinations symtoms across two consecutive visits. Kaplan‐Meier curves of ten‐year dementia‐free survival probability were generated for MBI‐psychosis versus those with no NPS prior to dementia diagnosis. Cox proportional hazard models were implemented to assess the risk of dementia, adjusted for age, sex, education, race, APOE e4 status, and clinical cognitive diagnosis. Interaction terms were included for relevant demographic variables. Secondary analyses were implemented to compare the risk associated with MBI‐psychosis to MBI without psychosis.ResultThe final sample consisted of 3,446 participants with no NPS (age = 73.1±9.6; 63% female; 13.2% MCI), and 58 with MBI‐psychosis (age = 74.9±9.9; 55.2% female; 69% MCI). MBI‐psychosis was associated with lower chance of dementia‐free survival over ten years and 3.36 times greater risk for dementia compared to no NPS (CI:2.19‐5.15, p<0.001). Moderation analysis revealed that in NC, those with MBI‐psychosis were at 8.15 times greater risk of dementia than those with no NPS (CI:2.57‐25.88, p<0.001). In MCI, the MBI‐psychosis‐associated dementia risk was 3.08 times greater (CI:1.95‐4.85, p<0.001). In the secondary analysis comparing MBI‐psychosis to MBI without psychosis (n = 2068), MBI‐psychosis was associated with 2.29 times greater risk of dementia (CI: 1.52‐3.4, p<0.001).ConclusionAlthough psychosis is an infrequently endorsed MBI domain, when present, it is associated with substantial risk for dementia. This risk differs between cognitive strata and is significantly greater when MBI‐psychosis emerges in NC versus MCI. The emergence of persistent psychotic symptoms in later life should be flagged for clinical attention, and a dementia assessment considered.
Electrophysiological signatures of memory depletion in mild cognitive impairment
Authors: Chino Brenda N , Cuesta Pablo , Pacios Javier , Torres Lucia , Doval Sandra , Dolado Alberto Marcos , Fuertes Miguel Yus , Fernández Ricardo Bruña , Maestú Fernando 
Published: June 2023

AbstractBackgroundMCI diagnosis does not necessarily imply the development of dementia. For this reason, characterizing the MCI profile is fundamental to the early identification of electrophysiological markers associated with a higher risk of developing Alzheimer’s Disease (AD). Longitudinal studies demonstrated that the delay recall measure is a good predictor of conversion and is one of the most common manifestations of the preclinical stage. This study has for purpose compared the power spectrum in the resting‐state of MCI and their relationship with neuropsychological and structural measures.MethodWe compared the power spectrum in resting‐state eyes‐closed magnetoencephalographic of 93 MCI participants (aged from 64 to 87) recruited from the Hospital Universitario San Carlos (Madrid, Spain). According to their memory performance in delay recall, the sample was split into (i) ‘moderate’ MCI (n = 52) group and (ii) ‘severe’ MCI (n = 41) group. The groups did not differ in age or years of education.ResultsThe severe MCI patients showed higher theta power than patients with moderate MCI were significant differences between both. Also, moderate MCI correlated significantly with years of education (rho = ‐0.31, p < 0.02) and TMT A time (rho = 0.40, p < 0.004). In the Severe MCI group, the theta power showed significant correlation with MMSE (rho = ‐0.43, p < 0.001) and total hippocampus (rho = 0.41, p < 0.001).ConclusionLoss of delay recall performance seems to be associated with electrophysiological alterations that can be used as non‐invasive markers of AD progression.
Non‐verbal communication of nursing home residents and care staff
Authors: Khan Zunera , Da Silva Miguel Vasconcelos , Testad Ingelin , Ballard Clive G 
Published: June 2023

AbstractIntroductionPeople living with dementia (PlwD) in nursing homes (NH) have complex needs with impairments in cognition, communication, and daily function. Complex needs may arise with impairments in communication and difficulty in expressing needs. PlwD often experience neuropsychiatric symptoms (NPS) with poor quality of life (QoL), which can be impacted by impairments in non‐verbal communication (NVC). NVC plays a key role in improving communication and engagement with PlwD. This study examines current NVC practices in NH between PlwD and care staff.Methods225 NH from the Care Home Research Network, King’s College London were invited to take part on an online anonymous questionnaire. The questionnaire included 13 questions on NVC and NH demographics. Care staff provided information on communication cues used between residents and staff during instrumental care and social activities. The use of NVC was rated on a Likert scale.ResultsThirty‐two NH completed the questionnaire, with 56% having 40‐90 beds. 9% of staff reported the use of verbal communication, 25% reported using combined verbal and NVC, whilst majority reported using NVC to communicate with residents (66%). The most observed NVC in residents was facial expressions (71.9%), followed by eye expression (53.1%) and touch (50%). Other NVC included the use of pitch, hand gestures and head nods (37%). Staff NVC cues included facial expressions (81.3%), eye contact (81.3%), hand gestures (75%), pitch of voice and head nods, (both, 66%). Furthermore, 34% of the staff used body language to assist residents with NPS, whilst 28% used touch. During social activities, facial expressions were used very often (78.1%) by residents, followed by head nods, touch and hand gestures (46%). Whilst receiving care, facial expressions were reported very often (68.8%). Other common cues involved touch (50%) and eye contact (41%).ConclusionNH residents and staff use a broad range of NVC channels to interact with one another and was the most reportedly used strategy. Developing interventions to improve communication between staff and PlwD should prioritize NVC, given its extensive use. Improving NVC would facilitate care staff to address needs better, reduce NPS and improve QoL.