bluuebunny/crossref_metadata_2025 huggingface dataset:
Title: Histochemical, immunohistochemical and behavioural demonstration of the potential of Zingerone to ameliorate cognitive decline in animal model
Authors: OVIOSUN AUGUSTINE , Anyanwu Emeka Godson , Oviosun Ezinne Chidinma , Memudu Adejoke Elizabeth
Published: December 2023

Background

Scientific evidence has revealed that dementia, cognitive impairment and Alzheimer’s disease (AD) is associated with increased oxidative stress and neuroinflammation leading to neurodegeneration. Zingerone has strong antioxidant and anti‐inflammatory potentials linked to possible neuroprotective effect.This study is to determine the modulatory mechanism of zingerone in cadmium induced cognitive decline by assessing memory using novel object recognition text, neuroinflammation biomaker‐ IL‐6, TNF‐alpha, Glial fibrillary acidic Protein (GFAP) in the PFC.

Methods

Thirty (30) adult male Wistar rats used were grouped into six (6) groups, n = 5 as follows; Control group (A), AD model was given 5mg/kg of cadmium for seven days (B), 100mg/kg of zingerone (C) for 14 days, the treatment study groups D‐F were given 5mg/kg of cadmium for seven days and treated using varying dose of zingerone for 14 days (50mg. 100mg and 200mg). Neurobehavioral test for memory and learning done using Novel object recognition. Left prefrontal cortices were homogenized for neuroinflammatory biomaker‐ (IL‐6) and (TNF‐alpha). Fixed prefrontal cortices were processed and stained using histological stain and immunohistochemical stain for astrocytes using glial fibrillary acidic protein (GFAP). Behavioral test data were analyzed using ANOVA, post hoc test and significance set at p<0.05.

Results

Zingerone effectively reversed cadmium induced cognitive decline characterized by reduced discrimination index, a marked increase in neuro‐inflammatory biomaker (IL‐6 and TNF‐α). However 200mg/kg of zingerone had a significance effect as compare to the two doses. Zingerone significantly downregulated GFAP expression activities and reduced neuronal cell loss the PFC.

Conclusion

Zingerone potential to repair cognitive impairment is associated with modulation of neuroinflammatory biomakers that result in improved cognitive function in the PFC.
Effect of Virgin Coconut Oil on Cognition of Mild‐to‐moderate Alzheimer’s Disease Patients with APOE ε4 Allele
Authors: Fernando Malika , Silva Renuka , Fernando Binosha , de Silva Asita , Wickremasinghe Rajitha , Dissanayake Asoka , Martins Ralph N , Williams Shehan
Published: December 2023

Background

Virgin coconut oil (VCO) is an excellent source of medium chain fatty acids and thus, a potential natural ketogenic agent that can be used to substitute glucose in Alzheimer’s disease (AD) brain, in which the glucose metabolism is compromised. High content of polyphenols in VCO will also support to reduce inflammation and oxidative stress associated with AD. The aims of this double‐blind placebo‐controlled trial were to investigate the effect of VCO on cognition in mild‐to‐moderate AD patients and the association of apolipoprotein E (APOE) ε4 genotype on the outcome.

Method

Study participants were 120 mild‐to‐moderate AD patients [Mini‐Mental State Examination (MMSE) score = 15‐25, age ≥65 years], randomly allocated to either treatment or control groups and orally fed 30 mL/ day of VCO as the treatment and a same amount of canola oil as the placebo for 24 weeks. Cognition was assessed by MMSE, Montreal Cognitive Assessment (MOCA), and executive clock drawing task (CLOX) at the baseline and at the end of the intervention. APOE genotyping was conducted at the baseline. Fasting lipid profile and glycated hemoglobin (HbA1C) levels were analyzed at the baseline and at the end of the intervention.

Result

There was no significant difference in the post‐intervention changes of cognitive assessment scores, lipid profile and HbA1C levels between the treatment and control groups. The MMSE scores of the APOE ε4 carriers in the treatment group was improved compared to the non‐carriers (change of MMSE = 2.37, p = 0.021), whereas there was no difference in the control group. In both treatment and control groups, the lipid parameters were not compromised during the intervention.

Conclusion

Oral supplementation of 30 mL/day of VCO for 24 weeks did not improve cognition of mild‐to‐moderate AD patients compared to canola oil. However, VCO improved the MMSE scores of APOE ε4 carriers compared to non‐carriers. Consumption of VCO was safe as it did not compromise lipid parameters.
Fukushimura Brain Bank ‐Nursing home based brainbank project in Japan‐
Authors: Kaneda Daita , Ogawa Norihiro , Kanesaka Takeshi , Hishida Chie , Sakurai Keita , Akatsu Hiroyasu , Yamamoto Takayuki , Yoshio Hashizume
Published: December 2023

Background

The Fukushimura (welfare village), located in Toyohashi city, Japan, is a unique complex of various nursing home facilities including dementia homes, Day‐care houses, homes for disabled and mentally retarded, and the Fukushimura Hospital. This village is totally managed by private sector, the Sawarabi Medical Cooperative. About 800 elderly people reside in this area. The hospital plays a pivotal role within the village and acts as the central facility for each nursing homes.

Fukushimura BrainBank (FBB) was established in 1990. The neuropathological investigation of FBB was initially conducted by Kenji Kosaka, who reported cortical Lewy bodies first. Our research institute was approved in 2004 by the Ministry of Education, Culture, Sports, Science and Technology, as one of the non‐governmental institutes which is permitted to apply for governmental grants.

Method

All the medical records and radiological images from the nursing home to hospital are stored in the research institute and accessible for the researchers to evaluate the psychological symptoms observed by carers in the long duration of the disease. The brain MRI of 1.5 Tesla was used for evaluating 3D‐volumetric T1WI and diffusion tensor imaging.

For collecting CNS specimens, the brains are separated into two hemispheres, one for neuropathological analyses with using several antibodies for beta‐amyloid, phosphorylated tau, alpha‐ synuclein, and TDP‐43. Modified gallyas‐silver staining is applied for evaluating argyrophilic grain disease. The other hemispheres are stored for frozen sections. Retinal tissue is collected with optional consent.

Result

The number of autopsy became over 30 cases per year. Most of the patients had dementia. Of note, geriatric residents with mentally retardation or cerebral palsy from childhood were included. At the end of 2022, more than 800 of frozen brains with detailed medical record are stored in FBB and readily available for research. The neuropathology database share the same coding system for Japanese Brain Bank Network for Neuroscience Research (JBBNNR).

Conclusion

The challenge of FBB will play a unique and important role to clarify cliniconeuropathological correlation of the nursing home residential with various geriatric conditions with 3D(Disability, Dementia, and Developmental disorders).
Analysis of multi‐dimensional cognitive function of different sexes in the middle‐aged and elderly people at high altitude
Authors: Zhu Aiqin , Liu Wenzeng
Published: December 2023

Background

To explore the overall and multi‐dimensional cognitive function of middle‐aged and elderly people and gender difference analysis of its influencing factors under hypoxia environment.

Method

From January 2018 to December 2021, using cross‐sectional study design, all participants from Xining, Qinghai Province (with an average altitude of 2,500m) who have lived for more than 20 years were selected.General data questionnaire survey, laboratory collection, overall and multi‐dimensional cognitive function assessment were conducted.

Result

A total of 500 middle‐aged and elderly people were included in this study, 299 males and 201 females, with an average age of 64.17 ± 10.58 years. Compared with women, there were more men working in civil service, earning more than 5000 months, smoking and drinking, accompanied by hypertension and diabetes (P<0.01, P<0.001), but Geriatric Depression Scale(GDS)and Pittsburgh sleep quality index (PSQI) scores were significantly lower (P<0.01).Compared with women’s multiple cognitive domains, scores of Mini mental state examination(MMSE), Complex Figure Test Delay Recall(CFT‐DR), Digit Span Forward(DSF) and Digit Span Backward(DSB) in men were higher (P<0.05, P<0.01), while scores of Trail Making Test (TMT‐A and TMT‐B) were significantly lower (P<0.01, P<0.001).The neutrophil lymphocyte ratio (NLR) and homocysteine (HCY) in peripheral blood were higher than those in women (P<0.05, P<0.01). Covariance analysis showed after adjusting for education level that scores of MMSE and situational memory (CFT‐DR) of men in different age groups were higher than those of women, while scores of attention (TMT‐A) and executive ability (TMT‐B) were lower than those of women (P<0.05, P<0.01). After adjusting for age, scores of MMSE and CFT‐DR of men in primary school, middle school and high school were higher than those of women (P<0.05, P<0.01). With the influence of education level, men’s TMT‐A scores showed a trend of lower (P<0.05, P<0.01), while women’s TMT‐A scores changed little.TMT‐B score of men was lower than that of women in the four education stages (P<0.05), but there was no trend for men and women to optimize with the increase of education level.

Conclusion

Middle‐aged and elderly people of different sexes living in high altitude hypoxic environment may have different multidimensional cognitive decline.
Language, Subjective Cognitive Decline and Help Seeking in Latinx
Authors: Chapman Silvia , Rentería Miguel Arce , Hokett Emily , Gonzalez Christopher , Seblova Dominika , Zahodne Laura B. , Marquine María J. , Brickman Adam M. , Manly Jennifer J. , Cosentino Stephanie
Published: December 2023

Background

Subjective cognitive decline (SCD) is a marker of Alzheimer’s disease and related dementia (ADRD) risk, as well as a reason why older adults seek medical help. However, whether the concept of SCD has utility in Latinx populations has been questioned because SCD’s inconsistent associations with cognition in this population. Measurement factors, such as how we ask about SCD (e.g., age‐anchoring) and person factors (e.g., preferred language) may influence the reported level of measured SCD and/or its association with cognition and help‐seeking.

Methods

Participants included 699 (50 years and older) Latinx individuals enrolled in the Offspring study of Racial and Ethnic Disparities in Alzheimer’s Disease. Participants completed two independent SCD measures that queried if memory had become worse (general SCD) and if it had become worse compared to others their age (age‐anchored SCD). Memory was assessed via the Selective Reminding Test (SRT) total and delayed raw scores. Help‐seeking was assessed by one item that asked if individuals had talked to a nurse/doctor about their cognitive concerns. In a series of linear and logistic regressions, we evaluated the cross‐sectional relationship between 1) SCD (general and age‐anchored) and memory performance and 2) SCD and help‐seeking. Models were stratified by preferred language (English‐speakers/Spanish‐speakers) and adjusted for age, sex, education, and medical burden.

Results

Spanish‐speaking Latinx participants were on average older, had less educational attainment, had greater medical burden, and reported more general SCD, but not age‐anchored SCD, than English‐speaking Latinx participants. Memory scores did not differ across language groups. General SCD was associated with help‐seeking in Spanish‐speakers only. Greater age‐anchored SCD was associated with lower SRT total score in English‐ (R2 = 0.158, B = ‐4.289, CI = ‐8.342,‐0.236) and Spanish‐speakers (R2 = 0.178, B = ‐5.889, CI = ‐10.875,‐0.904), as well as greater help‐seeking in both groups (English‐speaking: R2 = 0.078, B = 0.842, CI = 0.056,1.740; Spanish‐speaking: R2 = 0.277, B = 2.202,CI = 1.571,2.833).

Conclusions

Across language groups, age‐anchored SCD was consistently associated with memory performance and help‐seeking among Latinx adults. In contrast, general SCD was associated with help‐seeking only in Spanish‐speakers, and not associated with memory performance. This study is the first to demonstrate the utility of age anchoring SCD assessments within both English‐ and Spanish‐speaking Latinx individuals.
Identification and replication of gene‐by‐stress interaction associations with Alzheimer’s disease and related dementias
Authors: Singh Abanish , Arbeev Konstantin , Yashkin Arseniy Pavlovich , Mengel‐From Jonas , Schupf Nicole , Akushevich Igor , Yashin Anatoliy I
Published: December 2023

Background

Several mechanisms have been hypothesized for the pathogenesis of Alzheimer’s disease and related dementias (ADRD); however, we are still far from effective prevention and treatment of the disease, thus more basic research is needed to understand the etiological neuropathogenesis. We hypothesized that a part of increased ADRD‐risk could be due to a complex interplay of genes and daily‐life psychosocial stress.

Method

We used the Health and Retirement Study (HRS) surveys and Medicare‐linked data for the discovery analysis and the Long‐Life Family Study (LLFS) dataset for replication analysis, creating a synthetic stress measure using the algorithm based on stress proxy‐indicators, as described in Singh et al., 2015. The two datasets were compared by evaluating samples’ stress levels and socioeconomic status. We performed the HRS gene‐by‐stress discovery GWAS analyses on age‐at‐onset of ADRD using linear regression with SNP, STRESS, SEX, and ancestry principal components as other terms in model. We fitted the same regression model in the LLFS replication analysis, adjusting it additionally with field centers and Huber–White familial clustering.

Result

The HRS GWASs resulted in associations at p‐value of order 10−8 in both Blacks and Whites. Although most of the top 25 significant SNPs were mapped to non‐coding regions, we identified four characterized genes (BCR, MCC, KCNQ5, and DCP2) in Whites and three genes (EMCN, DPYD, and INSYN2A) in Blacks. Published literature from human and experimental studies suggested that five out of the eight genes were known for their association with neurodevelopmental disorders including Autism, intellectual disability, but also for cancers including colorectal carcinoma, gastric carcinoma, and leukemia. Although LLFS samples presented higher socioeconomic status and lower stress levels compared to HRS samples, the associations of one‐third tested SNPs from HRS Whites replicated in LLFS samples.

Conclusion

Our findings suggest that daily‐life stress may contribute to the risk of ADRD via complex interactions with genes. The associations with non‐coding genetic variants may indicate their influence through gene‐regulatory roles. In addition, the associations observed with cancer genes may possibly point towards the involvement of a common mechanistic feature, e.g., angiogenesis, which needs to be investigated further.
Clinical and genetic characteristics of patients with very early onset frontotemporal dementia
Authors: Friedberg Adit , Ramos Eliana Marisa , Bonham Luke W. , Knudtson Marguerite V. , Castruita Ale , Lopez Lucia , Li Yi , Geschwind Daniel H. , Seeley William W. , Yokoyama Jennifer S. , Miller Bruce L
Published: December 2023

Background

Frontotemporal dementia (FTD) spectrum disorders may occur in patients who are under 45 years old, often posing a diagnostic challenge, yet little is known about the clinical presentation and underlying genetic causes in this age group.

Method

As part of a prospective study focused on FTD, 780 participants met the research criteria for an FTD spectrum disorder between 2002‐2021. Of these, 40 patients (5.1%, 18 females) presented with age at onset < 45 years and constituted the very early onset frontotemporal dementia (VEO‐FTD) group. Their research records were reviewed to delineate their clinical characteristics. A panel of 40 dementia and amyotrophic lateral sclerosis‐associated genes was screened for pathogenic genetic variation using standardized methods.

Result

Behavioral variant of frontotemporal dementia was disproportionally represented in the VEO‐FTD group (n = 35, 87.5%) suggesting selective vulnerability of the social‐emotional brain networks to frontotemporal lobar degeneration underlying neuropathologies in this age range. The median age at first symptom was 39 (interquartile range (IQR) = 32‐42.2) years, and the median diagnostic delay from symptom onset was 4 (IQR 2‐8.25) years. Initial misdiagnosis with a primary psychiatric disorder was prevalent, occurring in 17 (42.3%) of patients, and was diverse including mood, psychotic, anxiety, and addictive disorders. In five patients (12.5%), positive psychotic symptoms were reported, mostly as a presenting symptom or arising within a year from the first symptom. Among the VEO‐FTD patients, 18 (45%) carried C9orf72, MAPT or UBQLN2 pathogenic variants.

Conclusion

FTD spectrum disorders may occur under the age of 45 and are often misdiagnosed. The high prevalence of monogenic causes in this age group warrants timely genetic testing, especially in the era of emerging gene‐specific therapies.
Cognitive and Socio‐Demographic Factors Related to Subjective Cognitive Decline in Native Americans
Authors: Dixon Bradley J. , Moll Allison C. , Woodard John L.
Published: December 2023

Background

Subjective cognitive decline (SCD) is commonly reported in neuropsychological evaluation, but self‐reported SCD can be influenced by anosognosia and depressed mood. Cognitive decline reported by a close informant, such as a spouse, may be more predictive of objective cognitive decline than a patient’s self‐report (Bellaali et al., 2021). Recent research comparing how racial and ethnic groups report SCD found strong evidence that Native Americans and their close informants reported SCD more frequently than White and Black Americans (Dixon & Woodard, N.D.). This study investigates whether unique socio‐demographic or cognitive variables could account for this phenomenon.

Method

Participants were selected from the National Alzheimer’s Coordinating Center (NACC) database. Participants were cognitively healthy at baseline, at least 65 years of age, and had an informant who lived with or visited the participant weekly (N = 9355). Participant racial groups included White Americans (n = 7770), Black Americans (n = 1517), and Native Americans/Alaskans (n = 68). Pairwise comparisons compared objective cognitive performance on the Mini‐Mental State Examination (MMSE), clinician‐determined functional decline, level of independence, educational attainment, self‐reported anxiety, Geriatric Depression Scale (GDS), and history of tobacco and substance abuse between each racial group using Bayesian contingency tables and t‐tests to find reliable evidence supporting the null or alternative hypothesis.

Result

Group comparisons indicated no reliable differences between Native Americans and the other racial groups on clinician‐determined functional decline, level of independence, self‐reported anxiety, tobacco use, and substance abuse (BF10 < 3). White Americans had significantly higher educational attainment and performed better on the MMSE (BF10 > 100) than Black and Native Americans. Native Americans exhibited reliably higher GDS scores than White (BF10 = 5.5) and Black (BF10 = 10.4) Americans.

Conclusion

The greater rate of SCD reported by Native Americans and their close informants compared with White and Black Americans may be related to significantly higher rates of depressive symptoms reported by Native Americans/Alaskans. Careful evaluation of mood symptoms may be particularly important for clinicians working with Native American/Alaskan patients to differentiate between SCD and objective cognitive impairment.
Suboptimal sleep efficiency and duration predict faster cognitive decline in cognitively unimpaired older adults
Authors: Pivac Louise N , Brown Belinda M , Doecke James D , Weinborn Michael , Sohrabi Hamid R , Gardener Samantha L , Bucks Romola S , Maruff Paul , Masters Colin L , Rowe Christopher C , Martins Ralph N , Rainey‐Smith Stephanie R
Published: December 2023

Background

Research indicates a role for suboptimal sleep, in cognitive ageing. An increasing, though inconsistent body of evidence has associated aspects of suboptimal self‐reported sleep quality with poorer cognitive performance. The current study investigated whether self‐reported sleep quality parameters predict the slope of domain specific cognitive performance.

Method

Participants were drawn from the Australian Imaging, Biomarkers and Lifestyle study of ageing. Linear mixed effect model (LMM) analyses were conducted on 525 cognitively unimpaired, older adults (M = 74.1, SD = 5.5, 56.4% female), characterised by apolipoprotein E (APOE) ε4 status, with baseline self‐reported sleep characteristics. Comprehensive cognitive assessments were conducted over a minimum 3 timepoints (range 29.64 ‐ 98.16 months). All models included random slopes, random intercepts, interaction effects for time, and APOE ε4 carriage, with each model adjusted based on the model of best fit for each cognitive outcome variable of interest.

Result

Following Bonferroni correction, sleep duration <6 hours and sleep efficiency <65% in the whole cohort, and in APOE ε4 non‐carriers, forecasted accelerated decline in attention and speed of processing. In the same groups, greater sleep efficiency (%) forecasted greater preservation within the attention and speed of processing domain. No associations were observed for other sleep variables or cognitive domains of interest.

Conclusion

These findings suggest a role for self‐reported suboptimal sleep efficiency and duration in the early stages of cognitive decline, represented by declining attention and speed of processing performance, in cognitively unimpaired individuals. Additionally, short sleep duration and poor sleep efficiency may increase future risk of cognitive decline independent of APOE ε4 carriage. Our findings also suggest the potential utility of self‐report screening for sleep efficiency and duration as a marker for increased risk of declining attention and speed of processing performance. Individuals with suboptimal sleep may benefit from an intervention to improve sleep efficiency and duration to lessen future risk of cognitive decline.
Tributyrin oral administration significantly attenuates the loss of intestinal butyrate‐producing bacteria and the ensuing cognitive dysfunction associated with Alzheimer’s Disease pathogenesis in 3xTg‐AD mice
Authors: Rao Aakarsha V. , Ghare Smita S. , Chilton Paula M. , Charpentier Benjamin T , Petrosino Joseph , Hoffman Kristi L , Greenwell J Caleb , Tyagi Neetu , Behera Jyotirmaya , Wang Yali , Sloan Lucy J , Zhang JingWen , Gobejishvili Leila , Whittemore Scott R , Shields Christopher B , Cooper Gregory , McClain Craig J. , Barve Shirish
Published: December 2023

Background

Alzheimer’s Disease (AD) development is linked to the loss of overall gut microbial diversity. However, the specific alterations are only beginning to be examined. In this regard, decreases in intestinal butyrate‐producing bacteria have been indicated by pre‐clinical and clinical studies in AD. The current work, employing the 3xTg‐AD mouse model examined the causal association of loss of butyrate‐producing bacterial communities with cognitive dysfunction associated with AD pathogenesis.

Method

Cecal samples from tributyrin (TB) treated and untreated female 3xTg‐AD mice were used to perform metataxonomic analysis by sequencing the 16S rRNA gene (V4 region) on a large‐scale Illumina MiSeq platform. Inferred metagenomics analysis was performed using the PICRUSt2 pipeline. TB treatment (oral gavage, 2mg/kg, twice a week) was initiated at 6‐months of age until 17‐months. Spatial and short‐term memory functions were tested using the Y‐maze and Novel Object Recognition Test (NORT).

Result

Metataxonomic analysis showed an age‐dependent, significant decline in alpha diversity represented by measures of OTUs, Chao‐1 and Shannon Index from 2‐ to 18‐months. Additionally, age‐dependent changes in gut microbial composition were demonstrated by a significant decrease in the Firmicutes‐to‐Bacteroidota (F/B) ratio. Further analysis of specific features of the gut microbiome demonstrated an age‐dependent decrease in total butyrate‐producing families within the Firmicutes phylum; particularly, a significant loss of critical butyrate producing family Ruminococcacea was identified. Predictive functional analysis using PICRUSt2 also showed a significant reduction in the abundance of specific bacterial genes involved in butyrate synthesis. Importantly, these age‐dependent markers of gut microbial dysbiosis coincided with diminished measures of spatial and short‐term memory. Notably, administration of TB, a butyrate pro‐drug, significantly attenuated the age‐dependent (i) decline in gut microbial diversity & butyrate‐producing bacteria and (ii) loss of spatial and short‐term memory.

Conclusion

The findings from this study identify that decline in total butyrate‐producing families is a key pathogenic feature of AD‐associated microbial dysbiosis and cognitive dysfunction. Importantly, these findings have the potential to inform the development of treatment strategies targeting gut microbial dysbiosis using TB, to prevent onset and development of cognitive decline in AD.
Investigating Alzheimer’s Disease‐Related Pathology in a Chronic Hyperglycemic Mouse Model
Authors: Ortiz Andrew Adonay , Hernandez Kimberly Stephanie , Suk Kyle Donghoon , Balsamo Brianna Michelle ,   Amanda Leisgang Osse, and Jefferson W Kinney
Published: December 2023

Background

Diabetes is a major risk factor for Alzheimer’s disease (AD). Hyperglycemia is the primary characteristic of diabetes. Hyperglycemia was induced in both young and aged mice. Following an incubation period, a hyperglycemic rescue was introduced to lower hyperglycemia, and to determine if hyperglycemia itself, or neuroinflammation as a result of hyperglycemia, increased AD pathology (i.e., hyperphosphorylated tau and reactive gliosis).

Method

Young (7‐month‐old; N = 24) and aged (18 month old; N = 24) C57BL/6J (wildtype) mice were injected with a low and staggered dose of streptozotocin (STZ) to induce sustained hyperglycemia. After a 9‐week incubation period of hyperglycemia (e.g., +250mg/dl), a group of mice were treated with Phloridzin (PZ) ‐ a drug that reduces hyperglycemia by preventing renal and intestine glucose uptake ‐ for two consecutive weeks to determine if hyperglycemia itself or the subsequent neuroinflammation, is what increase the risk for AD.

Result

STZ increased hyperglycemia levels; PZ lowered hyperglycemia levels. Both young and aged STZ, PZ, and STZ+PZ mice showed significantly differences in P‐S396‐tau/total, P‐T181‐tau/total, proinflammatory cytokines, and increases reactive microglia and astrocytes compared to controls.

Conclusion

PZ did not rescue hyperglycemic‐induced AD pathology.
Sleep‐mediated cognitive assessment and sleep architecture associations for real‐world diagnostic phenotyping of neurocognitive disorders
Authors: Karageorgiou Elissaios , Sykara Konstantina , Andronas Nikolaos , Alexoudi Athanasia , Devenopoulou Zoe , Pitman Julie , Karageorgiou Klimentini E
Published: December 2023

Background

Sleep disorders precede cognitive deficits by an average of four years in Alzheimer’s disease, and disrupted sleep has been associated with worse cognitive performance. We examined the association of a novel sleep‐mediated cognitive assessment to sleep architecture in people with and without cognitive impairment, towards earlier diagnosis of cognitive impairment.

Method

Forty‐three participants from the Sleep & Memory Center at the Neurological Institute of Athens cohort underwent a comprehensive evaluation that included polysomnography and pre‐ and post‐ sleep cognitive assessments of a novel short term verbal memory test as well as phonemic fluency testing. We examined the correlation of sleep‐mediated cognitive performance to sleep metrics of total sleep time, NREM/REM sleep, as well as respiratory metrics of Apnea‐Hypopnea Index and oxygen saturation during sleep.

Result

Sleep‐mediated spontaneous recall and phonemic fluency metrics were not associated to sleep architecture metrics. Instead, sleep‐mediated cued recall and recognition was positively associated to REM metrics of sleep time and relative REM/NREM ratio (R > 0.39; p < 0.039). On individual metrics, pre‐sleep verbal learning was positively associated to total sleep time (R > 0.30; p<0.05) as well as a larger REM/NREM ratio (R 0.52; p = 0.003). Finally, higher levels of oxygen during sleep, especially REM sleep, were associated with better pre‐sleep verbal learning (R > 0.39; p < 0.44).

Conclusion

Our results on people across a spectrum of cognitive abilities suggest that sleep‐mediated cognitive performance is significantly affected by shorter sleep times, and to a large extent these effects are dependent to the integrity of REM sleep. It is possible that both late evening learning abilities and sleep‐mediated memory reflects a person’s cholinergic capacity, as represented in subsequent REM sleep.
Vitamin D deficiency may increase the risk of developing cognitive impairment especially for APOE e4 non‐carriers
Authors: Kim Jiwon
Published: December 2023

Background

Vitamin D has been reported to play a role for neural protection and anti‐inflammation. However, its effects on the risk of cognitive decline has been inconsistent. Apolipoprotein E (APOE) could be a possible modulator of such influences as it takes part in the transport of cholesterol sharing a synthetic pathway with vitamin D and APOE e4 isoform is a well‐known significant risk factor of cognitive impairment. This study aimed to demonstrate the effects of vitamin D on incident cognitive impairment including mild cognitive impairment (MCI) and dementia and to explore its associations according to APOE e4 allele presence.

Method

We enrolled 1,271 cognitively normal community‐dwelling adults aged 60 years or older from the participants in the Korean Longitudinal Study on Cognitive Aging and Dementia. They were evaluated every two years from 2010 to 2018. We measured serum 25‐hydroxyvitamin D [25(OH)D] level and administered diagnostic assessment on MCI and dementia at every evaluation. We grouped the serum 25(OH)D into three levels as sufficient (> 30 ng/mL), insufficient (20 – 29.9 ng/mL), and deficient (< 20 ng/mL). We examined the associations of serum 25(OH)D level with the risks of incident MCI and dementia using Cox proportional hazard models adjusting for potential confounders. Then we also analyzed these effects in the APOE e4 non‐carriers and carriers separately.

Result

221 subjects showed a progression to MCI or dementia while 1,050 remained unchanged or improved cognitive function during follow‐up period. Participants who had deficient vitamin D concentration showed significant associations with a higher risk of cognitive decline (HR = 2.945, 95% CI = 1.088 – 7.970, p = 0.033) compared to sufficient 25(OH)D level group. APOE e4 non‐carriers who were vitamin D deficiency at baseline were 3.3‐fold more likely to suffer progression of cognitive impairment (HR = 3.308, 95% CI = 1.050 – 10.426, p = 0.041), whereas APOE e4 carriers did not show significant correlations of 25(OH)D levels with such progression (p > 0.05).

Conclusion

These results indicate that vitamin D deficiency may increase the risk of developing cognitive impairment and the effects would be greater for APOE e4 non‐carriers compared to APOE e4 carriers.
The influence of everyday acoustic environments on the challenging behaviour in dementia: a participatory observation study in Nursing Homes
Authors: Vriendt Patricia De , Talebzadeh Arezoo , Decoutere Ine , Mynsbrugge Tara Vander , Botteldooren Dick , Devos Paul , Aletta Francesco , Van de Velde Dominique
Published: December 2023

Objective

Dementia is a progressive illness characterized by cognitive and functional decline and often co‐occurs with a behaviour change. ‘Challenging behaviour’ (CB) is a group of behaviours, reactions and symptoms due to dementia, which can be challenging for the (professional) caregivers. The study aims to research the influence of acoustic on CB in people with dementia (PwD).

Design

An ethnographic design was used to study the daily life of PwD in their nursing homes with a specific focus on how people react to everyday environmental sounds.

Setting/participants

Thirty‐five residents were included in the sample based on a purposeful, homogeneous group characteristics sampling. Empirical data were collected using 24/7 participatory observations. The collected data were analyzed using a phenomenological‐hermeneutical Method: a naïve understanding, a structural analysis, and a comprehensive understanding.

Results

The onset of CB depends on whether the resident feels safe and is triggered by an excess or lack of stimuli. The excess or shortage of stimuli and whether and when it affects a person is highly personal. It depends on various factors, such as the person’s state and the time of day. In addition, the nature of the stimuli, familiarity or strangeness is also a determining factor for the onset and progression of CB.

Conclusion

CB is an indirect consequence of something that threatens the well‐being of the PwD. This unsettling feeling can find its cause in the acoustic environment. The results can form an essential basis for developing soundscapes to make the PwD feel safe and reduce CB.
Strategic Multimodal Intervention in at‐risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA): A cohort multiple randomised controlled trial (cmRCT)
Authors: Vishnu Venugopalan Y , Sinha Abhik , Gupta Anu , N Nilima , Srivastava MV Padma ,   SMRUTHI INDIA CONSORTIUM
Published: December 2023

Background

The major burden of dementia will be falling on Low and middle‐income countries in the next few decades. One of the major strategies to counter the rise in dementia burden is primary prevention, especially in at‐risk elderly individuals.

Method

Strategic Multimodal Intervention in at‐risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA) is designed as a Cohort Multiple Randomised Controlled Trial (cmRCT) under a prospective community‐based cohort in rural India with long‐term follow‐up over many years. The rural cohort will be established in four zones of India, under the Indian Council of Medical Research (ICMR), Model Rural Health Research Units (MRHRUs) at Himachal Pradesh (North), Tripura (East), Rajasthan (West) and Karnataka (South). We plan to recruit 10000 participants with age > = 55 years and CAIDE score > = 6. SMRUTHI INDIA will be established in 2 phases. Phase 1 involves establishing a cohort (phase 1a) and development, followed by validation of the multimodal care bundle (phase 1 b). The care bundle preparation will have a development phase, acceptability and adaptability phase followed by feasibility testing involving a pilot RCT in a single centre. Phase 2 involves testing multiple interventions in cmRCT, and the first intervention to be tested will be the multimodal care bundle. The primary outcome will be the incidence of all‐cause dementia.

Result

SMRUTHI INDIA will establish in parallel a large prospective rural cohort of at‐risk elderly in India and develop a culturally adapted and context‐specific multimodal care bundle. At the end of Phase 1, we will have the results of the pilot RCT on the feasibility of multimodal care bundle.

Conclusion

SMRUTHI INDIA is a landmark cohort multiple randomised controlled trial (cmRCT) which will assess multiple interventions for the primary prevention of dementia for the first time in India.

Funding: Department of Health Research, Indian Council of Medical Research (ICMR)
Development of a self‐help behavioural activation intervention INVOLVERA for people with dementia: a qualitative study
Authors: Blomberg Oscar , Svedin Frida , Brantnell Anders , Farrand Paul , von Essen Louise , Åberg Anna Cristina , Woodford Joanne
Published: December 2023

Background

Despite dementia being highly prevalent there is a lack of interventions to support people with dementia, and their informal caregivers, to live well. A guided, self‐help, behavioural activation‐based intervention (INVOLVERA), designed to support people with dementia to re‐engage with pleasurable, routine, and self‐care activities they have stopped doing, may represent a solution (Svedin et al., 2021). An innovative aspect of INVOLVERA is that support to the person with dementia to use INVOLVERA is provided by an informal caregiver, who themselves receives guidance from a healthcare professional. To enhance intervention acceptability and relevance interventions should meet the needs and preferences of the target population. Following Phase I (Development) of the Medical Research Council’s Framework for the development of complex interventions (Skivington et al., 2021), this study explores the needs and preferences of people with dementia, informal caregivers, and professional stakeholders to enhance the acceptability and relevancy of INVOLVERA for people with dementia.

Methods

Semi‐structured interviews and focus group discussions were held with people with dementia (n = 8), informal caregivers (n = 19), healthcare professionals (n = 18), and community stakeholders (n = 7). A written draft of INVOLVERA and proposed intervention delivery model were provided to participants. Open‐ended questions explored intervention content, language and intervention delivery preferences. Data were analysed using manifest content analysis.

Results

One overarching theme: Tailoring and flexibility, and three categories: Intervention process, material and context; Support and guidance; and Time derived from analysis. Results informed the following adaptations: (1) increased flexibility of intervention delivery (e.g., outside of traditional healthcare settings); (2) additional guidance and training to informal caregivers; (3) reduced written material (to minimise treatment burden); (4) modernisation of design and illustrations; (5) improved relevance of case stories and illustrations to the Swedish context; and (6) increased diversity of persons in case stories.

Conclusion

This study highlights the importance of developing interventions alongside stakeholders. We anticipate the approach will optimise the acceptability and relevancy of INVOLVERA. Next, we will examine the acceptability and feasibility of INVOLVERA.
Cognitively Healthy Centenarians are genetically protected against Alzheimer’s disease
Authors: Tesi Niccoló , Van Der Lee Sven J , Hulsman Marc , van Schoor Natasja , Huisman Martijn , Pijnenburg Yolande A. L. , Flier Wiesje M. , Reinders Marcel JT , Holstege Henne
Published: December 2023

Background

The prevalence of Alzheimer’s Disease (AD) increases with age, yet a small fraction of the population reaches ages beyond 100 years maintaining cognitive abilities, so‐called cognitively‐healthy‐centenarians. We aimed to uncover the genetic factors associated with such protection against AD, and to highlight the effects of AD‐associated variants during advanced aging.

Method

Previous Genome‐Wide‐Association‐Studies (GWAS) identified 86 single‐nucleotide‐polymorphisms (SNPs) associated with AD‐risk. We investigated the frequency of each SNP in 346 cognitively‐healthy‐centenarians (mean age 101.05±2.51), compared to 2,281 AD cases (mean age 67.96±9.84), 3,165 middle‐aged healthy controls (mean age 62.57±8.66), and we combined the SNPs into Polygenic Risk Scores (PRS) for each individual. Finally, we characterized the functional properties of the SNPs enriched/depleted the most in the centenarians.

Result

At the SNP level, centenarians were depleted with risk‐increasing SNPs and enriched with protective SNPs. The AD‐related PRS (excluding APOE SNPs) was significantly lower in centenarians; not only compared to AD (OR = 1.96, p = 4.07×10−26), but also to middle‐aged controls (OR = 1.29, p = 2.61×10−5). When including APOE SNPs these effects were even stronger (OR = 5.07, p = 6.15×10−71, and OR = 1.87, p = 4.67×10−17, for comparisons with AD and normal controls, respectively). The most depleted/enriched SNPs in centenarians functionally mapped to activation/regulation of immune response and endocytosis/phagocytosis. These SNPs were located near ANKH, TMEM106B, CLNK, EPDR1, WDR12, PLCG2, RIN3, CD2AP, MS4A, TREM2, ABCA7 and MAF.

Conclusion

The ability to reach advanced age without cognitive decline is influenced by AD‐associated genetic variants. An advantageous regulation of the brain’s immune system, intracellular protein trafficking, and endocytosis/phagocytosis may confer the strongest protection against AD and potentially other age‐related diseases.
Baseline characteristics and study progress of the CITA GO‐ON Study. A FINGER‐like Multidomain Intervention to Prevent Cognitive Decline in Spain
Authors: Ecay Mirian , Tainta Mikel , Iriondo Ane , Altuna Miren , Estanga Ainara , Clerigue Montserrat , Saldias Jon , de Arriba Maria , Lopez Carolina , Garcia‐Sebastian Maite , Barandiaran Myriam , Izquierdo Mikel , de Asteasu MIkel Lopez‐Saez , Reparaz‐Escudero Imanol , Gayoso Lucia , Etxeberria Usune , Gorostiaga Arantxa , Balluerka Nekane , Soroa Goretti , Aritzeta Aitor , Ros Naia , Capetillo‐Zarate Estibaliz , Alberdi Elena , Mar Javier , Vergara Itziar , Mateo‐Abad Maider , Martinez‐Lage Pablo
Published: December 2023

Background

The FINGER study demonstrated the efficacy of a non‐pharmacological multidomain intervention to prevent cognitive decline in at‐risk older adults. After a successful pilot feasibility study, in Q3 2021 we launched the CITA GO‐ON study, inspired by FINGER methodology to demonstrate the efficacy of a risk factor and lifestyles multimodal intervention to prevent cognitive decline in southern Europe. Here we describe the baseline characteristics of participants recruited in the study.

Method

The CITA GO‐ON study (ClinicalTrials.gov, NCT04840030) is a two‐year randomized, controlled trial. The primary aim is to reduce the risk of decline in cognitive functioning in the Neuropsychology Test Battery after two years by a multi‐modal intervention on risk factors and protective life‐styles as compared to standard health care. Inclusion criteria are: 60‐85 years old; CAIDE dementia risk score ≥ 6; cognitive frailty; no dementia. The multidomain intervention includes optimized control of cardiovascular risk factors; correction of polypharmacy; cognitive training; physical exercise program; socioemotional intervention; and promotion of adherence to the Mediterranean diet.

Results

To date, 1964 individuals completed pre‐screening using self‐administered online survey in REDCap (Research Electronic Capture) and 874 (44.5%) fulfilled criteria for an in‐person screening visit. Screening was successful in 477 of participants. Mean (SD) age is 66.24 (4.99), 13.26 (4.43) years of education, MMSE 28.27 (1.78), CAIDE score 7.48 (1.36), and 235 (49%) are men. Based on CAIDE components, at baseline, 287 (60%) showed high systolic blood pressure, 165 (35%) low physical activity, 122 (26%) high BMI, and 101 (21%) with high cholesterol. Regarding cognitive frailty, 144 (31%) presented low performance on brief cognitive testing (Memory Alteration Test ≤ 40 and/or Fototest ≤ 35), 186 (39%) presented memory complaints (Cognitive Change Index ≥ 20), and 147 (30%) showed both criteria. Currently, 191 have been randomly assigned to the control and 192 to the Intervention groups. So far, adherence to intervention activities is high, ranging from 73% to 97%, depending on the modality.

Conclusion

CITA GO‐ON Study recruitment strategy includes participants with high risk of dementia based on modifiable factors and in situation of cognitive fragility, with might increase the probability of obtaining positive efficacy results.
The natural history of subjective complaints, awareness and metacognition in AD
Authors: Cappa Stefano F , Ribaldi Federica , Chicherio Christian , Frisoni Giovanni B
Published: December 2023

Background

Subjective cognitive decline (SCD) is the self‐reported experience of decrease in cognitive function in absence of cognitive impairment. This condition is common in elderly subjects and is a frequent reason for referral to memory clinics. SCD is often considered as a stage antedating objective impairment, and an at‐risk condition for subsequent dementia. Recent large‐scale studies, however, support an increased risk only in subjects positive for Alzheimer’s disease (AD) biomarkers, confirming that SCD can be due to multiple mechanisms, including functional cognitive disorders.

Method

This work have reviewed the current research on the awareness of cognitive decline (ACD), with a focus on metacognitive abilities and on assessment tools. The findings from studies of ACD during the course of AD are also reviewed for their possible impact on clinical management.

Result

We propose that, in presence of normal cognitive performance, a subjective overestimation of objective cognitive performance may be a negative prognostic marker, while subjective overestimation of cognitive decline may be compatible with healthy aging or the presence of a functional cognitive disorder.

Conclusion

Longitudinal studies are needed to test the usefulness of metacognition measures to select SCD subjects for biomarker assessment and/or metacognitive training.
Early detection of mild cognitive impairment due to Alzheimer’s disease using combinations of an online cognitive assessment and blood biomarkers
Authors: Pei Zhong , Chen Weineng , Liu Ganqiang , Lin Cha , Su Fengjuan
Published: December 2023

Background

Accessible measurements to a large screening and early differentiation of mild cognitive impairment due to Alzheimer’s disease (MCI‐AD) from healthy elderly is increasing urgent with the prevalence of Alzheimer’s disease (AD) expanded.

Method

an online cognitive assessment (Memtrax) and MoCA were performed, on 99 clinically diagnosed cognitively normal (CON) and 101 MCI‐AD participants. The plasma levels of phosphorylated tau (p‐tau)181 and neurofilament light (NfL) and amyloid beta (Aβ)42/40 were measured using Simoa assay. The relevance between Memtrax and blood biomarkers were conducted by Spearman correlation analysis. Discrimination models were built using assorted machine learning approaches combining Memtrax with blood biomarkers, and model performance was measured using Area Under the Receiver Operating Characteristic Curve (AUC).

Result

The AUC of Memtrax and MoCA in differentiating MCI‐AD from CON was similar. Memtrax has a strong correlation with phosphorylated tau (p‐tau)181 and neurofilament light (NfL), while less related to amyloid beta (Aβ)42/40. Combining Memtrax and blood biomarkers, the AUC of best model reach to 0.975 (95% CI: 0.950‐0.999).

Conclusion

The combination of Memtrax and blood biomarkers is promising to the large screening and early detection in MCI‐AD.