bluuebunny/crossref_metadata_2025 huggingface dataset:
RXR agonist bexarotene modulates the cell‐fate and migration abilities of adult neural stem cells in vitro
Authors: Saibro‐Girardi Carolina , Matsubara Ingrid Scheibel , Santos Lucas , Bittencourt Reykla Ramon , Moreira José Claudio Fonseca , Gelain Daniel Pens
Published: June 2023

Background

Targeting the nuclear RXR receptors has been associated with brain‐specific roles with striking therapeutic potential for Alzheimer’s Disease (AD), with similar observations to its dimerization partners such as LXR and PPAR whose responses are also under influence of RXR activation. Treatment with bexarotene, a selective RXR agonist, leads to significant recovery of cognitive loss in variable mice AD‐like models ‐ and also activates neurodevelopment and plasticity pathways in adult mice brains. Our hypothesis is that neural stem cells (NSC) residing in the adult brain directly respond to bexarotene, leading to improved neurogenesis and other effects compatible with brain recovery.

Method

We employed an in vitro strategy using NSCs isolated from the subventricular zone of adult rats’ brains. Adult NCSs were treated with bexarotene from neurosphere proliferative stage to differentiated states, and the cell‐fate consequences were evaluated through morphometric analysis and immunofluorescence of cell markers.

Result

In proliferative stages, bexarotene‐treated adult NSCs exhibited increased cell outgrowth from neurospheres. Bexarotene treatment also led to changes in the cell fate of differentiating cells, with a marked increase in GFAP staining after differentiation. Relatively to newborn neurons, we found a decrease in DCX positive staining of neuroblasts after bexarotene treatment. However, Tuj1 staining of neurons was preserved. Neurite number, length, and bifurcations in differentiated neurons were unaffected by bexarotene.

Conclusion

Adult NSCs respond to bexarotene by increasing migration abilities and generating more GFAP+ cells. Results indicate that RXR activation by bexarotene in adult NSCs preserves, but does not activate, neuronal differentiation and neurite complexity. The significance of the increased GFAP+ glial cell population, as well as the decreased DCX+ young neurons, remains to be unrevealed. Finally, we did not observe clear bexarotene‐induced changes in neurosphere proliferation, but the effect of RXR activation over pluripotency in these cells needs further investigation. These findings address a gap in our knowledge regarding the brain effects of bexarotene, substantiating the search and possible application of RXR‐based approaches to AD.
Support for verbal memory reserve in women using an epigenetic marker of age acceleration
Authors: O'Shea Deirdre , Alaimo Hannah
Published: June 2023

Background

To determine whether characterizing men and women based on rates of biological aging indexed by DNA methylation “GrimAge” reflect differences on measures of verbal and non‐verbal memory.

Method

Cross‐sectional data from 1,930 adults aged 65 or older (mean age = 75, SD = 7.4, Male = 43%, non‐Hispanic White = 74.8%, non‐Hispanic Black = 13.5%, Hispanic = 9.6%, other race/ethnicity = 2.1%) were included. The standardized residual from regressing chronological age on the DNA methylation GrimAge clock as the measure of age acceleration. Slow and accelerated “DNAmGrimAgers” were defined as individuals below or above 1 SD of their sex‐specific GrimAge acceleration Mean, respectively. Individuals between these cutoffs were categorized as “normal agers” resulting in six different groups (i.e., 3 female and 3 male). Performances on measures of verbal and non‐verbal memory and processing speed were compared across these six different groups, controlling for education, depressive symptoms and chronological age. We reran analysis adjusting for processing speed.

Result

When comparing men and women’s performances based on their matching DNAmGrimAge category, there was no difference in processing speed or visual memory (e.g., accelerated male DNAmGrimAgers performed similarly to accelerated female DNAmGrimAgers on speed). In contrast, women, regardless of their DNAmGrimAge category, outperformed men on verbal memory measures (in speed and non‐speed adjusted models). Additionally, while accelerated female DNAmGrimAgers had significantly lower memory performances compared to slow female DNAmGrimAgers, this group difference was no longer significant in the speed‐adjusted models.

Conclusion

Women maintained a verbal memory advantage over men, despite different rates of age acceleration, which was not accounted for by faster processing speed. These findings strengthen prior support for verbal memory reserve that is specific to women. Thus, relying on verbal memory assessments in women at risk of Alzheimer’s disease (AD) may not be sensitive enough to detect hippocampal impairment in the earliest stages. However, performances on visual memory measures may be a more accurate representation of hippocampal function in women and should be included in assessments where AD is suspected.
Multidisciplinary characterization of potential inhibitors of the MSUT‐2 protein using molecular dynamics, mechanosensation assays, and deep AI‐based hit optimization for the treatment of Alzheimer’s disease
Authors: Ganesh Rithvik
Published: June 2023

Background

Alzheimer’s disease is a type of tauopathy, which is a broad category of diseases marked by abnormal aggregation and hyperphosphorylation of the tau protein. The MSUT‐2 protein has gained traction as a promising target for the treatment of tauopathies, given the protein’s RNA‐binding activity linked to tau aggregation. Previously in this research endeavor, using techniques like Quantum Machine Learning and Virtual Screening, 5 potential MSUT‐2 inhibitors have been identified from an initial set of 500,000 candidate compounds. The primary research aim is to further analyze these 5 potential hits using a new combination of computational methodologies and laboratory characterization.

Method

A myriad of tests were performed with strains of C. elegans (microscopic roundworms that are established models for neurodegeneration) to validate previous computational indications. A series of motion evaluations, mechanosensation assays, and behavioral assessments were performed with CL2319 C. elegans (mutated to overexpress neuronal tau) with all 5 compounds. One of the compounds, named R128, was found to improve the health and behavior of tau mutant worms across experimental assessments at increasing doses of the compound. A 100 nanosecond simulation of the MSUT2‐R128 complex using the GROMOS96 43a1 force field and SPC Water Model was used to computationally validate protein‐ligand stability based on RMSD fluctuation values. DeepFrag, a fragment‐based lead optimization tool with a deep convolutional neural network backend, was then used to generate 20 potential optimized compounds, nine of which were found to retain R128’s druglikeliness profile yet have improved binding affinities to MSUT‐2.

Result

This multidisciplinary workflow has uncovered a promising hit for the MSUT‐2 protein, named R128, with 9 optimized derivatives with improved drug‐like qualities. This methodology can be used to efficiently identify promising treatment candidates for new protein targets involved in neurodegenerative diseases, with the prospect of expediting the drug discovery process significantly.

Conclusion

To conclude, a translational approach, combining molecular dynamics, mechanosensation assessments with C. elegans, and an AI‐based hit optimization strategy has been used to identify new treatment candidates for Alzheimer’s disease. R128, a promising inhibitor for MSUT‐2 (an understudied target for Alzheimer’s disease), has also been identified in this study.
The interaction between APOE‐e4 gene and paid work for women in predicting ADAS 13 scores
Authors: Lee Lisa J , Liu Stephanie , Morin Ruth , Bennett Lauren
Published: June 2023

Background

The associated risk of Alzheimer’s disease linked to the APOE‐e4 gene is similar in males and females. However, there is a disproportionate rate of Alzheimer’s in women (two‐thirds) compared to men. Mayeda et al. (2020) found that women who worked for pay during early adulthood and midlife, whether married or unmarried, had a slower rate of memory decline in later life compared to women who did not work for pay. Although there has been much research on the association between type of paid work or work environment and dementia; for instance, work complexity, job control, and job strain, there has been little research that includes unpaid work in ascertaining its effect on women and neurocognitive functioning later in life. This study aims to find the interaction between paid work and the APOE‐e4 gene in predicting the risk for Alzheimer’s disease (operationalized as ADAS13 total score at baseline) in women.

Method

A two‐way ANOVA was performed using data at initial visit from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database for 340 female participants.

Result

There were significant main effects for APOE‐e4 gene on ADAS‐Cog‐13 total score (F (2,334) = 4.697, p = .010) as well as paid work on ADAS‐Cog‐13 total score (F (1,334) = 5.450, p = .020). The interaction between APOE‐e4 gene and paid work on ADAS‐Cog‐13 total was not significant (F (2,334) = 215.725, p = .091).

Conclusion

APOE‐e4 gene as well as unpaid work are independently linked to higher scores on the ADAS‐Cog‐13 (Alzheimer’s Disease Assessment Scale) for women. There is no interaction between APOE‐e4 gene and type of work on ADAS‐Cog‐13 scores for women.
Differences in rate of change of retinal structural and microvasculature parameters in parkinson’s disease compared to controls
Authors: Kundu Anita , Ma Justin , Robbins Cason B , Pant Praruj , Soundararajan Srinath , Stinnett Sandra , Scott Burton , Moore Kathryn , Grewal Dilraj S , Fekrat Sharon
Published: June 2023

Background

Prior cross‐sectional studies have revealed decreased macular perfusion density (PFD) and increased peripapillary PFD in Parkinson’s disease (PD). We assess longitudinal rate of change of retinal microvascular and structural parameters in PD vs controls with normal cognition.

Method

Subjects were imaged using Zeiss Cirrus HD‐5000 AngioPlex. Those with confounding medical or ocular comorbidities were excluded. Superficial capillary plexus (SCP) PFD and vessel density (VD) were assessed within ETDRS 6×6 circle, inner ring, outer ring and 3×3 circle and inner ring. SCP foveal avascular zone (FAZ) area was assessed. PFD, VD, FAZ, peripapillary retinal nerve fiber layer (RNFL), ganglion cell‐inner plexiform layer (GCIPL), and central subfield thickness (CST) were measured at 2 time points 1 year apart. Rate of change per year was calculated. Generalized estimating equations analyzed associations between rate of change of imaging parameters and PD.

Result

74 eyes of 40 patients with PD (60% male, mean age 67.47.9 years) & 149 eyes of 78 controls (28% male, mean age 70.35.8 years) were included. No demographic differences were observed between groups except higher proportion of females in controls (p = 0.001). PD had a greater decline in PFD in 6×6 circle (mean change per year = 0.021, control = 0.00, p = 0.001), 6×6 inner ring (PD = 0.018, control = 0.001, p = .007), 6×6 outer ring (PD = 0.022, control = 0.00, p = 0.001), 3×3 circle (PD = 0.016, control = 0.002, p<.001), 3×3 inner ring (PD = 0.016, control = 0.002, p<0.001). PD had greater decline in VD in 6×6 circle (mean change per year in PD = 0.72/mm, control = 0.054/mm, p = 0.006), 6×6 inner ring (PD = 0.636/mm, control = 0.048/mm, p = 0.03), 6×6 outer ring (PD = 0.746/mm, control = 0.054/mm, p = 0.005), 3×3 circle (PD = 0.939/mm, control = 0.006/mm, p<0.001), 3×3 inner ring (PD = ‐0.942/mm, control = 0.013/mm, p<0.001). PD had greater decrease in GCIPL (mean change per year in PD = 0.403µm, control = 0.128µm control, p = 0.01). There were no significant differences in rate of change in FAZ area, RNFL thickness, CST, and no significant differences in rate of change when stratified by PD severity.

Conclusion

PD may be associated with more rapid loss of retinal microvascular perfusion and vessel densities and more rapid thinning of GCIPL compared to normal aging in controls with normal cognition.
Rightward lateralization of frontal cortex tau pathologies is associated with late‐onset psychosis: A PET study with 18F‐PM‐PBB3
Authors: Kurose Shin , Takahata Keisuke , Moriguchi Sho , Tagai Kenji , Kubota Manabu , Sano Yasunori , Yamamoto Yasuharu , Endo Hironobu , Hirata Kosei , Matsuoka Kiwamu , Oya Masaki , Matsumoto Hideki , Kokubo Naomi , Koreki Akihiro , Suzuki Hisaomi , Ogyu Kamiyu , Mashima Yuki , Mimura Yu , Nakajima Shinichiro , Bun Shogyoku , Seki Chie , Takado Yuhei , Sahara Naruhiko , Onaya Mitsumoto , Mimura Masaru , Higuchi Makoto
Published: June 2023

Background

Several cohort studies have recently reported associations between late‐life psychosis and dementia, and postmortem studies have demonstrated that most individuals with late‐onset schizophrenia and delusional disorder had tau pathologies. The present study was aimed to assess the prevalence and topology of tau pathologies by positron emission tomography (PET) with a specific probe, 18F‐PM‐PBB3 (18F‐APN‐1607), in patients with late‐onset psychosis (LOP).

Method

We included LOP patients who experienced the first episode of psychosis after 65 years old and excluded those with dementia. Fourteen patients with LOC (74.2 ± 4.0 years old; 7 females and 7 males)and 16 age‐matched healthy controls (HCs) (72.6 ± 5.7 years old; 9 females and 7 males) underwent PET scans with 18F‐PM‐PBB3 and an amyloid‐β probe, 11C‐PiB. The radioprobe retention was calculated as standardized uptake value ratio (SUVR), and the laterality index (LI) of SUVR was estimated as [Left‐Right/(Left+Right)]. We compared 18F‐PM‐PBB3 SUVRs and LIs in the frontal, temporal, parietal, and occipital cortices between patients and HCs using an independent t‐test after Bonferroni correction (p‐value ≤ 0.05/4).

Result

All HCs were negative for 11C‐PiB‐PET. By contrast, unequivocally increased 18F‐PM‐PBB3 retentions were found in 4 out of 4 11C‐PiB‐positive patients (100%) and 7 out of 10 11C‐PiB‐negative patients (70%) with variable localizations. Tau topologies in four 11C‐PiB‐positive cases were characteristic of Alzheimer’s disease and consisted of limbic predominant (N = 2), medial temporal lobe‐sparing (N = 1), and lateral temporal (N = 1) deposition subtypes. Meanwhile, tau topologies in 7 11C‐PiB‐negative cases were composed of lateral‐posterior diffuse (N = 3), posterior mild (N = 2), lateral temporal local (N = 1), and progressive supranuclear palsy‐like (N = 1) accumulations. None of the target regions exhibited significant differences in 18F‐PM‐PBB3 SUVR between patients and HCs, reflecting the heterogeneous distributions of tau deposits in patients. There was significant rightward lateralization of tau pathologies indicated by a reduced LI in the frontal cortex (P = 0.0093) but not the other cortical regions.

Conclusion

Our findings indicate that LOP is associated with tau topologies of diverse Alzheimer’s and non‐Alzheimer’s disease subtypes. The rightward lateralization of tau pathologies in the frontal cortex might be involved in the development of psychotic manifestations.
Comparing visuospatial construction ability of MoCA and MMSE in cognitive assessment of patients with dementia of Alzheimer’s type
Authors: Rai Pooja , Singh Indramani L. , Singh Tara , Tiwari Trayambak , Joshi Deepika
Published: June 2023

Background

The ability to see an object or picture as a set of parts and then to construct a replica of the original from these parts is known as visuospatial constructive cognition. Examples of visuospatial construction include drawing, buttoning shirts, constructing models, making a bed, and putting together furniture that arrives unassembled. Visuospatial construction is a central cognitive ability. At the same time, there are enormous individual differences among people in their ability to perform visuospatial constructive tasks. The MoCA had greater sensitivity than MMSE in detecting MCI versus HCs (; however, specificity was lower for the MoCA than MMSE.

Method

The present study has considered visuospatial construction ability in cognitive neuropsychological screening tool. The neuropsychological screening tool were Mini‐mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The intersecting pentagons copy sub‐item was administered as part of the MMSE whereas there was cube figure to copy where subjects have to initially convert a two‐dimensional contour to a three‐dimensional cube. The sample consisted of 15 patients with mild Dementia of Alzheimer’s type.

Result

The result showed that both the MoCA and the MMSE were successful in differentiating between patients with and without cognitive domain deficits and cognitive impairment. The scores in visuospatial construction ability on MoCA and MMSE are different on visuospatial domain which on further analysis showed significant differences in cognitive performance.

Conclusion

The cognitive scores of mild Dementia of Alzheimer’s patient differs which showed the differences in the ability to complete a cognitive task as and thus revealed greater sensitivity of MoCA as compared to MMSE.
Co‐design of an Aboriginal Health Practitioner‐led dementia prevention program (DAMPAA) using a Theory of Change framework
Authors: Arriero Irene Mateo , Lalovic Alex , Flicker Leon , Almeida Osvaldo P , Thompson Sandra , Etherton‐Beer Christopher , Hill Keith , LoGiudice Dina , Cox Kay L , Milte Rachel , Ratcliffe Julie , Pestell Carmela , Dowden Glennette , Bynder Michael , Bulten Samuel , Yappo Lynette , Markey Lesley , Lin Ivan , Woods Deborah , Smith Kate
Published: June 2023

Background

Dementia prevalence and incidence in Aboriginal Australians is three to five times that of the general population. Many of the known risk factors for dementia in this population are modifiable (e.g., head injury, hypertension, previous stroke and poor mobility). However, there is currently no evidence‐base on how to delay or prevent cognitive decline and dementia in Aboriginal Australians. Therefore, a comprehensive program to target dementia risk factors in this population is required.

Method

In partnership with three Aboriginal Community Controlled Health Services (ACCHS) in Western Australia, we have developed an Aboriginal health practitioner‐led health program (DAMPAA) to target key dementia risk factors for Aboriginal people over 45 years. The DAMPAA program was co‐designed by the research team, Elders and Aboriginal community‐controlled organisations. Qualitative data to inform the co‐design was collected through ACCHS staff workshops, Elders yarning groups and interviews with DAMPAA Aboriginal and non‐Aboriginal researchers using a Theory of Change framework. Additionally, a small pilot study was conducted in 2020, which included participant exit interviews conducted by Aboriginal researchers. Qualitative data from all data sources was analysed thematically by a qualitative researcher, and member checked by two DAMPAA Aboriginal researchers and the Elders Governance group.

Result

The DAMPAA program includes group physical activity, education, goal setting and medication management. Program enablers identified by ACCHS, research staff and participants include (but not limited to) group Aboriginal community controlled organisation based walking and yarning sessions, with additional activities such as aqua aerobics, tai chi and boot scooting, a buddy system for home exercising, connecting with others, transport, healthy food, being Aboriginal led, and the ACCHS partnership. An additional enabler identified by the Elders governance group include Aboriginal language education sessions. Program barriers identified include (but not limited to) family commitments, caring for grandchildren, travel for funerals and other appointments and participant contact details changed.

Conclusion

The barriers and enablers identified from participants, ACCHS and DAMPAA staff have informed the development of the program protocol. DAMPAA will be evaluated through a randomised controlled trial implemented at four sites in Western Australia and process evaluation using a Theory of Change framework.
The Link between Brain age and Alzheimer’s Disease development using different neuroimaging modalities
Authors: Doering Elena , Antonopoulos Georgios , Hönig Merle C. , van Eimeren Thilo , Eickhoff Simon B. , Patil Kaustubh , Drzezga Alexander
Published: June 2023

Background

Brain age (BA) provides a proxy of general brain health through the prediction of chronological age (CA) from neuroimaging data of healthy individuals. During aging, the adult brain undergoes changes both on the morphological and metabolic level. Here, we compare the link between BA predicted from morphology (structural MRI) or metabolism (18F‐FDG‐PET) and cognitive function, as well as pathophysiological measures of Alzheimer’s disease (AD) in cognitively normal individuals (CN) and patients with mild cognitive impairment (MCI).

Method

Several machine learning algorithms were trained to predict BA from 256 matched MRI or 18F‐FDG‐PET scans of CN from the Alzheimer’s Disease Neuroimaging Initiative. Trained algorithms were then used to predict BA in a test sample of CN (n = 123) and MCI (n = 621). Partial spearman correlations between brain‐predicted age difference (BA – CA; BPAD) and composite scores of cognitive function (memory: ADNI‐MEM; executive function: ADNI‐EF), as well as pathophysiological measures of AD (amyloid (cerebrospinal fluid (CSF) and PET) and tau pathology (CSF tau and p‐tau)) were subsequently calculated in these test samples correcting for sex.

Result

18F‐FDG‐PET‐ and MRI‐predicted brain age showed a mean absolute error of 2.77 and 1.81 years in CN, respectively.

ADNI‐MEM scores declined with increasing 18F‐FDG‐PET‐BPAD, while ADNI‐EF scores declined with increasing MRI‐BPAD in CN.

Higher BPAD was significantly associated with worse cognitive function in MCI in both modalities, while stronger associations were found for MRI‐BPAD and cognitive function.

18F‐FDG‐PET‐, but not MRI‐BPAD was correlated with CSF amyloid load in CN.

In MCI, higher BPAD from both modalities was associated with more amyloid and CSF p‐tau pathology, while only MRI‐BPAD was significantly associated with an increase of CSF tau pathology. Associations of MRI‐BPAD and pathology were generally stronger.

Conclusion

Brain age can be reliably predicted on the basis of 18F‐FDG‐PET and MRI. Amyloid‐neuropathology, predisposing for AD, as well as initial memory decline is related to features of advanced BPAD in 18F‐FDG‐PET ahead of clinical onset of disease. Onset of tau‐related neurodegeneration and of objective cognitive decline is more strongly associated with signals of increasing BPAD on MRI.
Optimizing the social engagement of persons with mild cognitive impairment: insight from a process evaluation of an empowerment‐based psycho‐behavioral program
Authors: Lin Rose S.Y. , Yu Doris S.F. , Li Polly W.C. , Chau Patsy P.H.
Published: June 2023

Background

Enhancing social engagement has been suggested as a promising approach to enhance the quality of life and prevent the progression to dementia among older adults with mild cognitive impairment (MCI). However, their cognitive deficits and the concomitant neuropsychiatric symptoms, particularly depression and apathy, may not only mass their incompetency and inadequacy to engage in social events, but also lead to withdrawal from leisure activities and social interaction. Therefore, a randomized controlled trial of an empowerment‐based psycho‐behavioral program was conducted among persons with MCI, and its process evaluation may provide insight into optimizing social engagement among this preclinical cohort.

Method

A qualitative process evaluation was conducted for a 13‐week, group‐based, psycho‐behavioral program focused on promoting knowledge enhancement, cognitive coping, and stress adaptation among persons with MCI and was guided by empowerment model through a goal‐setting approach. A purposive sample of 22 participants who reported differential changes on NPS after completing the program attended an individual, semi‐structured, face‐to‐face interview from December 2020 to October 2021. A semi‐structured interview guide was developed to elicit their views on the engagement experience and perceived effects of the program. All interviews were audio‐taped, transcribed verbatim, and analyzed by thematic analysis.

Result

Three themes emerged: (1) barriers to social engagement, (2) environmental factors to increase social engagement, and (3) psychosocial context to increase social engagement. The participants identified fear of social rejection, lack of available social activities, and perceived difficulties in keeping appointments as barriers to social engagement. As supported by the empowering environment of the program, the participants received a clear roadmap and protocol to overcome their cognitive deficits and enhance their participation in social activities. The memory aids provided by the program, such as whiteboards and memos, were highly useful in tracking upcoming appointments and social events. The program also offered them a platform to develop new friendships and interact with peers facing similar challenges.

Conclusion

This study highlighted the effects of a psycho‐behavioral program on improving cognitive and psycho‐social well‐being among persons with MCI. The findings also underscored the potential of the empowerment approach to optimize cognitive coping and social engagement in this preclinical cohort.
Visual search in patients with Alzheimer’s disease and mild cognitive impairment: Kitchen scanning task
Authors: Akkoyun Müge , Koçoğlu Koray , Boz Hatice Eraslan , Tüfekci Işıl Yağmur , Ekin Merve , Akdal Gülden
Published: June 2023

Background

We aimed to evaluate the visual scanning patterns of patients with Alzheimer’s Disease (AD) and amnestic mild cognitive impairment (aMCI).

Method

29 AD patients (mean age 72,5±7.9 years), 34 aMCI patients (mean age 70,6±6,7 years), and 32 healthy control (HCs) (mean age 68,5±6,2 years) were given neuropsychological tests (NT) with five domains and eye movements were recorded when doing a kitchen scanning task. Firstly, participants were asked to find a single object in the three kitchen pictures shown and secondly to prepare scrambled eggs, Turkish coffee and breakfast. The first 3 pictures are 6000 ms, the other 3 pictures are shown for 10000 ms. The kitchen materials required for the given tasks were identified as an area of interest. Fixation duration, fixation count, first fixation duration, and saccade count were recorded with EyeLink 1000 Plus video eye tracker.

Result

There was no significant difference in age and education between aMCI, AD patients, and HCs (p<0,05). In the first task, AD patients were a statistically decreased in fixation duration than aMCI and HC groups (p = 0,001), and in saccade count compared to HC’s (p = 0,031). Also, patients with AD were a statistically increased number of fixations in the out of interest area compared to aMCI and HC groups (p = 0,009). In the second task, AD patients had significantly decreased fixation duration compared to aMCI and HC groups (p = 0,006), and in first fixation duration than HC’s (p = 0,02). In addition, AD patients had significantly decreased number of saccades in the out of interest area compared to HC’s (p = 0,048). All measured saccadic parameters were weakly correlated with cognitive test scores (r = 0,2‐0,4).

Conclusion

This study showed that patients with Alzheimer’s disease performed fewer saccades when visual scanning and scanned the visual field less with a shorter fixation duration compared to aMCI and HC’s. This may be related to the deterioration of visual memory and visual attention in AD patients.
The relationship of apathy with daily life activities, quality of life and caregiver burden in patients with dementia
Authors: Kilicaslan Kimya , Tulek Zeliha , Gurvit Ibrahim Hakan
Published: June 2023

Background

Apathy is one of the most common neuropsychiatric symptoms in dementia. The aim of this study is to evaluate apathy and its relationships with activities of daily living, quality of life and caregiver burden in patients with dementia.

Method

The research was conducted in a descriptive analytic type. The sample consisted of 88 patients with a definite diagnosis of dementia attending outpatient clinic of a university hospital in Istanbul between October 2019‐March 2020 and their family caregivers. Depressive patients (assessed by Cornell Scale) and paid caregivers were not included. Apathy Evaluation Scale‐Clinician (AES‐C) and Informant (AES‐I) Forms, Neuropsychiatric Inventory (NPI), Mini Mental Test (MMSE), Quality of Life in Alzheimer’s Disease Scale (QoL‐AD), Lawton Instrumental (Lawton IADL) and the Katz Activities of Daily Living Scale (Katz ADL) were used for patients and Caregiver Burden Inventory (CBI) was used for caregivers.

Results

The mean age of the patients was 73.11±11.68, and diagnosis duration was 3.9±3.1 years, 64.8% had Alzheimer’s type dementia and 53.4% (n = 47) had mild‐1 dementia. The mean MMSE score was 16.4±6.6, NPI‐Symptom score was 16.6±13.7, AES‐C score was 52.9±10.2. The QoL‐AD score was 28.8±6.1 in patient evaluation and 27.6±6.4 in caregiver evaluation. The AES‐C scores were correlated with NPI, MMSE, ADL, Cornell, QoL‐AD, and CBI. Apathy was found to be an important predictor of both the patient’s QoL and CBI.

Conclusion

In dementia patients, apathy was found to be associated with patient’s activities of daily living, quality of life, and caregiver burden. It is recommended that patients be evaluated for apathy.
Saccadic eye movement in individuals with ultra high‐risk psychosis and bipolar disorder
Authors: Ekin Merve , Koçoğlu Koray , Boz Hatice Eraslan , Akkoyun Müge , Tüfekci Işıl Yağmur , Yalınçetin Berna , Bora Emre , Akdal Gülden
Published: June 2023

Background

The purpose of the study is to examine saccadic eye movements, and the relationship with motor functions based on the cerebellar connection among individuals with ultra‐high‐risk of psychosis and bipolar disorder (UHR‐P, UHR‐BD) and healthy controls (HC).

Method

The study included 20 UHR‐P (mean age 21.95±3.38), 20 UHR‐BD (mean age 21.45±4.27), and 19 HC (mean age 24.84±3.95). Participants had been selected from cases clinical‐high‐risk criteria in interviews made with The Structured Interview of Psychosis Risk Syndromes (SIPS) and Bipolar Prodrome Symptom Interview and Scale (BPSS). Correct and incorrect count, amplitude and latency of anti‐saccade were used to evaluate eye movements. Eye movement data were recorded from the right eye using an EyeLink 1000 Plus eye‐tracker. In addition, Brief Motor Scale (BMS) was used to evaluate motor functions.

Result

The number of correct saccade of anti‐saccade showed a significant difference between HC and UHR‐BD (p = 0.021). The Correct anti‐saccades were strongly correlated with motor function in UHR‐BD (r = ‐0.754, p<0.000). There was a moderate positive correlation between incorrect responses of anti‐saccade and motor function in UHR‐BD. (r = 0.455, p = 0.044). Motor functions indicated statistically significant differences between HC and high‐risk groups (p = 0.002 and p< 0.000). No significant relationship was found between anti‐saccade latency and amplitude and motor functions. (p> 0.05).

Conclusion

We indicated that patients with ultra‐high risk had saccadic inhibition and motor coordination‐sequencing problems. This may be related to the dysfunctions in the cerebellum. The results are preliminary data of an ongoing study.
Music in Dementia Assessment Scales (MiDAS) portuguese version: Translation, cultural adaptation and psychometric study
Authors: Sousa Lídia , Moura Barbara , McDermott Orii
Published: June 2023

Background

Music in Dementia Assessment Scales (MiDAS) is an observational, dementia‐specific, visual analogue scale, developed to measure musical experiences of patients with dementia (PwD). Derived from qualitative data of focus groups and interviews with PwD, carers, care home staff, and music therapists, it revealed acceptable to good psychometric properties in a preliminary study. We aim to describe the translation and cultural adaptation of MiDAS to European Portuguese, and the results of a preliminary psychometric evaluation.

Method

A rigorous ten step approach, suggested by the authors of MiDAS, was followed, for translation and cultural adaptation. It included: two forward translations and a back translation by a bilingual professional translator; harmonization with versions in different languages; testing and debriefing the final version with health professionals.

For the psychometric study, care home residents with dementia attended a bi‐weekly group music‐based intervention (Mbi), for up to ten sessions. Intervention coordinators and care home staff completed MiDAS ratings at every session and the Quality‐of‐Life Scale (QoL‐AD) was completed at three time‐points. Inter‐rater and test‐retest reliability, internal consistency, concurrent and construct validity of MiDAS were evaluated.

Result

No major changes have been made to the actual content of MiDAS. Minor adjustments were made in wording and additional instruction details were added, to increase clarity and adequacy to the Portuguese setting.

A total of 529 MiDAS‐PT forms (Staff = 235, Therapist = 294) were completed during the psychometric study. Our analysis indicated low therapist inter‐rater and test‐retest reliability, good internal consistency, low concurrent validity, and good construct validity. High factor loadings between the five MiDAS items (Interest, Response, Initiation, Involvement, and Enjoyment) were found.

Conclusion

Overall, Portuguese health professionals considered MIDAS‐PT user friendly and intuitive in terms of content and structure. More research is needed, with a larger sample, providing a more in‐depth psychometric characterization.
APOEε4 genotype boosts neurodegenerative structural changes in medial temporal lobe areas in adults with Mild Cognitive Impairment
Authors: Fernández Miguel Ángel Rivas , Lindín Mónica , Zurrón Montserrat , Díaz Fernando , Aldrey Jose M. , Galdo Santiago
Published: June 2023

Background

Apolipoprotein E ε4 allele (APOEε4) is considered the major genetic risk factor of Alzheimer´s Disease (AD). Structural magnetic resonance imaging (sMRI) studies demonstrated that, compared to APOEε4 non‐carriers, APOEε4 carriers display structural changes in lateral and medial temporal lobe (MTL). However, the knowledge about the impact of this genotype on hippocampal subfields is still limited. The present sMRI study aimed to evaluate volumetric and cortical thickness differences between adults with mild cognitive impairment (MCI) APOEε4 non‐carriers compared with MCI‐APOEε4 carriers.

Method

Twelve MCI‐APOEε4 non‐carriers (mean age: 70.33 years, SD: 5.12) and ten MCI‐APOEε4 carriers (mean age: 72.70 years, SD: 6.38), diagnosed as MCI according Petersen criteria (Petersen, 2004; Albert et al., 2011), underwent neuropsychological assessment, cerebrospinal fluid, genetic and MRI examinations. MRI surface‐based morphometry analyses was conducted with the FreeSurfer software to evaluate volumetric and thickness differences in the hippocampal subfields and its surrounding MTL areas.

Result

Compared with MCI‐APOEε4 non‐carriers, the MCI‐APOEε4 carriers group showed a significant reduced volume in several areas of the left hemisphere. Specifically, in this hemisphere volumetric changes were found in the entorhinal cortex, the whole hippocampus and in its head, body and tail; the head of presubiculum, the head and body of subiculum, the CA1, CA3, CA4 subfields, the granulate cell of the molecular layer of dentate gyrus and the molecular layer of the hippocampus. This group also displayed a significant reduced volume in the right body of CA3 subfield.

Conclusion

These results suggest that, in MCI adults, the presence of the APOEε4 genotype may have an additional neuropathological impact on the structure of brain regions of the MTL with a critical functional role in episodic memory, the most affected neurocognitive system in Alzheimer’s disease (AD). Particularly, the left MTL would show higher vulnerability to neurodegenerative changes in the prodromal stage of AD.
Compensation and network dedifferentiation in amnestic mild cognitive impairment (a‐MCI): A resting‐state study
Authors: Varela‐López Benxamin , Galdo‐Álvarez Santiago , Fernández Miguel Ángel Rivas , Díaz Fernando
Published: June 2023

Background

The diagnostic entity of amnestic mild cognitive impairment (a‐MCI) presents an annual conversion rate to Alzheimer’s disease of about 10‐15%. Considering that a‐MCI may correspond to the prodromal stage of Alzheimer’s disease, understanding the associated functional brain changes becomes relevant in the context of early detection of this type of dementia. Consequently, the aim of this work was to explore the changes in brain functional connectivity associated to a‐MCI, of 3 closely related brain networks (Default Mode Network ‐DMN‐, Salience Network ‐SAL‐, Central Executive Network ‐CEN‐) by means of resting‐state functional magnetic resonance imaging (rs‐fMRI).

Method

The sample was composed of 59 participants, comprising a control group of 30 (13 ♀) participants and an a‐MCI group of 29 (12 ♀) participants. An independent component analysis (ICA) was performed for the 3 proposed networks (DMN, SAL & CEN) using the CONN toolbox.

Result

Compared with the control group, the a‐MCI group showed increased functional connectivity: A) within the CEN in the left inferior frontal gyrus, being this increase positively correlated with the cognitive state of the a‐MCI measured through the Mini‐Mental State Examination (MMSE); and B) between the DMN and SAL in frontal regions (orbital anterior and middle frontal gyri), being correlated with worse scores in immediate, short‐term and long‐term free recall measured through a verbal learning test (TAVEC).

Conclusion

The present data support that the a‐MCI participants developed not only compensatory processes mediated by the CEN, but also non‐compensatory effects mediated by DMN and SAL functional interactions.
Patterns of cognitive performance in old adult community sample from Nigeria
Authors: Ucheagwu Valentine A
Published: June 2023

Background

Patterns of cognitive impairments were studied in old adult sample in a view to understanding the roles of modifiable risk factors on cognition.

Method

Two hundred participants (115 males; age: 60‐74) were recruited. Domains of cognitive performance were measured with the UDS Version 3.

Result

Result showed significant difference between diabetic (DG) and non‐diabetic (NDG) groups on Craft Story immediate, Benson recognition, category fluency animal and total category score with DG performing significantly better than NDG. Significant differences were found between hypertensive (HG) and non‐hypertensive (NHG) groups on number span forward Total correct and number span forward Length of correct. On the other hand, we showed significant interaction of depression and dementia history on Benson design recognition with participants that reported depression and history of dementia performing significantly worse than other groups. Depressive group (DPG) differed significantly from non‐depressive group (NDPG) on category fluency animal and total category fluency. Significant interaction effects were found on depression and history of dementia on category fluency (animal and vegetable) and total category score with participants reporting depression and positive history of dementia performing significantly worse on the measures. However, participants reporting history of dementia performed significantly better than non‐history participants on MoCA test. Further, we showed significant differences among 3 divisions of occupation: skilled (SK), semi skilled (SMK) and unskilled (USK) on craft story immediate (: SK = 25.79; SMK = 19.23; USK = 24.77), delayed (: SK = 20.27; SMK = 14.84; USK = 19.72), number span forward (total correct and length of correct), number span backward (total correct, length of correct and total aggregate score) with skilled occupation performing significantly better that the other two. The same were found for category fluency (animal and vegetable) and Control Oral Word Association Test.

Conclusion

Our findings suggest the important roles of diabetes, occupation and interaction of depression and dementia history on some domains of cognitive performance and the need to modify these variables for healthy cognition in old adults.
Pre‐Clinical Investigation of Repaglinide Nanoparticles in High Fat Diet with streptozotocin induced memory impaired rats
Authors: Wadhwa Geetika , Taliyan Rajeev
Published: June 2023

Background

Diabetes Mellitus is a metabolic disorder characterized by insulin resistance with several metabolic abnormalities which trigger neuronal complications, neurodegeneration, and cognitive impairments. Repaglinide (REP) is an insulinotropic, neuroprotective agent with short‐action and poor absorption characteristics. Hence, the present study was aimed to investigate the efficacy of REP‐loaded lipid polymer‐hybrid nanoparticles (REP‐LPHNPs) in High Fat Diet low dose of Streptozotocin (HFD‐STZ) induced cognitive deficits wistar rats model.

Methods

The REP‐LPHNPs were prepared by the solvent evaporation method. The optimization and statistical analysis of LPHNPs were done using Design‐Expert software by the response surface Box‐Behnken design. Animals were fed with HFD‐STZ (30 mg/kg; i.p) to induce cognitive impairment. Treatment was carried out for 28 days in separate groups viz, negative control, positive control, pure REP (4 mg/kg, p.o.), REP‐LPHNPs (4 mg/kg, p.o.). Behavior assessment parameters like passive avoidance test, spatial navigation task, probe trial, and spontaneous locomotor activities were performed. Further, biochemical parameters were performed with oxidative stress markers. Moreover, a pharmacokinetic (PK) study was performed, and parameters were assessed by Phoenix WinNolin CerteraTM (Pharsight, U.S.A; version:8.0) with non‐compartmental modelling.

Results

The REP‐LPHNPs having phospholipid coated nanoparticles with a hydrophobic polymer core were prepared successfully and characterized thoroughly. The REP‐LPHNPs showed improved PK parameters, e.g., t1/2 (h) and AUC, which were found increased by twice than the REP. The REP‐LPHNPs significantly reduced the cognitive impairment in wistar rats by assessing behavioral and biochemical tests. It was observed that nanocarrier showed improved efficacy in spatial learning and memory impairment as compared to the REP.

Conclusion

In summary, the downsides of REP were successfully by loading into LPHNPs. The study demonstrates that REP‐LPHNPs improved the PK parameters and showed better neuroprotective effects than REP alone in HFD with STZ induced cognitive deficits in encountered wistar rats.
Levels of astrocyte‐derived glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in the cerebrospinal fluid within the early stages of Alzheimer´s Disease
Authors: Cetindag Arda Can , Priller Josef , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Jessen Frank , Duzel Emrah , Bürger Katharina , Perneczky Robert , Teipel Stefan , Christoph Laske , Spottke Annika , Heneka Michael T. , Schipke Carola G. , Bauer Chris , Peters Oliver
Published: June 2023

Background

The quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer´s disease (AD). A substantial problem in the early diagnosis of AD is that clinical symptoms as measured by neuropsychological tests appear only after massive cell loss has already occurred in the brain. However, when the disease manifests, abeta‐ and tau‐protein levels have already become static. In this study, we asked whether concentrations of the astrocyte‐derived proteins glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in CSF might serve as markers of pathophysiological events and astrocyte reactivation in the course of AD. Although, there are some previously studies reporting high GFAP levels in cerebrospinal fluid of AD group, the CSF levels of GFAP and S100B in the early course of the AD have not been reported.

Methods

We measured the levels of GFAP and S100B in the CSF of healthy control subjects (n = 90), first degree relatives of AD (parent or sibling, n = 46), subjective memory decline (SCD) (n = 211), mild cognitive impairment (MCI) (n = 114) and AD (n = 65) patients in a well‐structured cohort (DELCODE Cohort), which has a larger sample size than previous studies.

Results

After comparing the CSF levels of GFAP in the study groups, we found that healthy controls had significantly lower GFAP levels than AD patients (p = 0.001, Figure 1) and the MCI patients (p = 0,004, Figure 1). It might prove to be a very important evidence of the role of astrogliosis in early stages. Furthermore, no significantly differences were found in levels of S100B, although S100B mean values show also gradual increasing from SCD to AD (Figure 2). As a note to the reader, we also found that there was low correlation between the levels of glial markers (GFAP und S100B) and markers of classical biomarkers (Aβ‐42, Ratio Aβ‐42/Aβ‐40, Total‐τ, Phospho‐τ‐181) of neurodegeneration in the disease course.

Conclusion

This result may prove the role of early reactive astrocytes in early stages of disease. And this finding could lead to develop another treatment concepts targeting the early reactive astrocytes.