bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma total bilirubin in patients with Alzheimer’s disease: An observational study
Authors: Ramdane Said , Ramdane Abderraouf
Published: December 2021

Background

Bilirubin, the primary end product of the heme cleavage pathway, is currently regarded as a major physiologic antioxidant with important cytoprotective properties. Oxidative stress is a well established contributing factor in the development of Alzheimer's disease (AD). In the present study, we aimed to compare serum bilirubin levels in patients with AD and healthy elderly controls, and to analyze the potential relationship between serum total bilirubin levels and dementia severity in AD patients.

Method

Measures of fasting serum total bilirubin levels were studied in 68 patients with AD (34 women; mean age 71.4±5.8 years; range 60‐82) (DSM‐IV; NINCDS‐ADRDA criteria) from a private ambulatory of neurology, recruited in a community elderly in Skikda‐Algeria (2017‐2020); and in 68 elderly controls (34 women; mean age 70.4±6.3 years; range 58‐82). Dementia severity was assessed by the clinical dementia rating scale‐CDR global score.

Result

The mean (±SD) plasma total bilirubin level was 0.72±0.13 (Range 0.49–1.08) among AD group and 0.66±0.11 (range 0.48–1.02) mg/dL among control group; (p= 0.0029). By gender, plasma total bilirubin level was higher in cases compared to controls both in men 0.75±0.14 vs. 0.67±0.13 mg/dL respectively, (p= 0.027); and in women 0.70±0.12 vs. 0.64±0.10 mg/dL; (p= 0.040). Patients with mild AD (Mean age 68±3.7 years) showed significantly higher levels of plasma total bilirubin compared with patients with moderate AD (Mean age 77.4±3.6 years): 0.77±0.13 vs. 0.64±0.09 mg/dL respectively (one way ANOVA, p= 0.0001). Plasma total bilirubin level was significantly negatively correlated with dementia severity, r= ‐0.4503; (95% CI for rho: ‐0.621; ‐0.238), p= 0.0001. By gender r= ‐3564; (p= 0.038) for men; and r= ‐0.5481, (p= 0.0007) for women.

Conclusion

These data indicate that plasma total bilirubin level is increased in AD compared to controls, and inversely correlates with dementia severity. Patients with mild AD have higher total bilirubin levels (Within clinical normal range) than patients with moderate AD. These results suggest that serum total bilirubin level may provide additional information for predicting development of AD. We speculate that a possible beneficial physiologic antioxidant role for bilirubin could be operating during earlier stages of AD and gradually fades with disease progression.
A retinal deep phenotypingTM platform to predict the cerebral amyloid PET status in older adults
Authors: Soucy Jean‐Paul , Chevrefils Claudia , Osseiran Sam , Sylvestre Jean‐Philippe , Lesage Frédéric , Beaulieu Sylvain , Pascoal Tharick A. , Provost Karine , Arbour Jean Daniel , Rhéaume Marc‐André , Villeneuve Sylvia ,   Prevent‐AD Research Group, Nasreddine Ziad S. , Rosa‐Neto Pedro , Gauthier Serge , Robillard Alain , Chayer Céline , Black Sandra E. , Kertes Peter J. , El Shahawy Hossam , Scott Christopher J.M. , Bhan Aparna , Martins Ralph N. , Shah Tejal M. , Gupta Sunil M. , Calvin Kirsten , Hsu Gregory , Lowe Val J. , Chen John J. , Ritter Aaron
Published: December 2021

Background

As the only optically accessible part of the central nervous system, the retina represents an intriguing opportunity for the detection of biomarkers for Alzheimer’s disease (AD). This study evaluated the performance of the Retinal Deep PhenotypingTM platform, a digital biomarker platform comprising a hyperspectral retinal camera and image analysis algorithms, for the detection of likely positron‐emission tomography (PET) amyloid status (negative or positive) in older adults. A set of phenotypic features that correlates with the cerebral amyloid status as determined by amyloid PET scan were identified and used to train a classifying algorithm.

Method

Hyperspectral retinal images acquired with a Mydriatic Hyperspectral Retinal Camera from 194 participants (age ≥ 50 years), including cognitively normal and cognitively impaired (mild cognitive impairment and dementia) across 5 imaging sites were processed in order to train the model. Of these 194 participants, 73 individuals (38%) were amyloid‐positive, as confirmed by unanimous readings of PET scans by a panel of 3 expert reviewers. The pre‐processed hyperspectral images were segmented into various anatomical sites, and a texture‐based approach was used to extract several thousands of spatial‐spectral features. The most relevant features for the classification task were selected using a minimum redundancy maximum relevance (MRMR) algorithm and used to train a linear support vector machine (SVM) classifier. A nested, cross‐validation technique was used to evaluate the performance of the classifier.

Result

The resulting model based on the 17 most significant features showed high performance to discriminate between amyloid positive and negative subjects with an area under the receiver operating curve (AUCROC) of 0.87 (95% CI: 0.83 – 0.92).

Conclusion

The Retinal Deep PhenotypingTM platform shows promise for detecting the likely cerebral amyloid PET status in adults 50 years and older from a simple, non‐invasive retinal scan and could provide an accessible means to identify individuals with abnormal cerebral amyloid in a clinical or drug development context. This phenotyping platform provides a flexible approach that could also be used for the detection of multiple biomarkers involved in cognitive decline from the same hyperspectral images of the retina.
Brain insulin signaling in persons with and without diabetes is associated with cognitive decline
Authors: Gwizdala Kathryn L. , Arvanitakis Zoe , Arnold Steven E. , Ahima Rexford S. , Bennett David A. , Newton Robert L , Carmichael Owen T.
Published: December 2021

Background

Peripheral insulin resistance is associated with increased risk of AD dementia, and postmortem measures of reduced insulin signaling in the brain have been linked to poorer cognition in AD‐related domains proximal to death. However, the relationship between brain insulin signaling and longitudinal cognitive decline over the years leading up to death is under‐studied. This study assessed the relationship between longitudinal change in domain‐specific cognition and brain insulin signaling in a clinical‐pathologic, community‐based cohort.

Method

Using a subsample of participants in the Religious Orders Study (75 with diabetes matched to 75 without diabetes), we examined data derived from annual cognitive assessments (mean age (years) baseline: 77.25 ± 6.34; final: 86.03 ± 6.14) and postmortem measures of brain insulin signaling. Neuropsychological testing was grouped to form a primary measure of global cognition, and five separate cognitive domains. Brain insulin receptor signaling was quantified via ELISA for the ratio of pS307IRS1 /total IRS1 (insulin receptor substrate‐1) “IRS1 phosphorylation”, ratio of pT308AKT1/total AKT1 (serine/threonine‐protein kinase) “AKT phosphorylation”, and immunohistochemistry for IRS1 cells/mm2, and pIRS1 at S616. Mixed effects regression models assessed per‐person mean level and rate of change (slope) in each cognitive domain, along with effects of brain variables, age at death, sex, and education on mean level, and effects of brain variables on change (the α was set at 0.025).

Result

Greater AKT phosphorylation had a trend‐level association with faster decline in global cognition (‐0.02 (0.01) 0.035). Greater AKT phosphorylation was associated with faster declines in working memory (‐0.02 (0.01) 0.015) and visuospatial ability (‐0.01 (0.01) 0.023) and at a trend level with faster episodic memory decline (‐0.03 (0.01) 0.026). Greater IRS1 phosphorylation was associated with slower decline in perceptual speed (0.02 (0.01) 0.023). Greater staining for pS616IRS1 was associated with faster visuospatial ability decline (‐0.02 (0.01) 0.020).

Conclusion

Brain insulin signaling measures are associated with cognitive decline in the years prior to death. Future work should further characterize these relationships and explore links of peripheral insulin resistance and cognitive decline and dementia.
Amyloid accumulation associated with worse performance of complex task
Authors: Keleman Audrey A. , Bollinger Rebecca M. , Ances Beau M. , Stark Susan L.
Published: December 2021

Background

The preclinical stage of Alzheimer disease (AD) is largely considered a clinically silent period that is detectable primarily through neuroimaging and biofluid biomarkers of amyloid and tau. We evaluated whether performance of complex daily activities is associated with amyloid accumulation as measured by positron emission tomography (PET) among cognitively normal (CN) individuals with or without preclinical AD.

Method

CN participants (Clinical Dementia Rating 0) from the Knight Alzheimer Disease Research Center performed three activity subtasks (shopping, checkbook balancing, and medication management) from the Performance Assessment of Self‐Care Skills (PASS) at their homes. They also had an amyloid PET scan using Pittsburgh Compound‐B within one year of completing the PASS. PASS subtasks were scored for independence, adequacy, and safety of performance. Nonparametric correlations were used to determine the associations between amyloid accumulation and performance on each subtask.

Result

Fifty‐six CN participants (mean age 74.8 years, 61% female, 87% white) were included. Median amyloid PET was 1.17 (interquartile range 1.07–1.63; standard cutoff for preclinical AD: 1.42). Amyloid PET accumulation was not associated with performance on the checkbook balancing or medication management subtasks of the PASS. Higher amyloid PET accumulation was associated with worse performance on the shopping subtask of the PASS.

Conclusion

This study suggests that a complex task, measured using a performance‐based test, may be associated with higher amyloid deposition. Performance‐based measures could potentially serve as a less expensive method for screening individuals who may likely benefit from further evaluation (plasma amyloid or PET amyloid). They could also lead to a better understanding of functional changes that may be occurring during the preclinical stage of AD.
Speech‐in‐noise perception is a marker of preclinical Alzheimer’s disease
Authors: Waters Sheena , Watson Cameron , Jacobs Benjamin M. , Foote Isabelle F. , Dey Sumit , Noyce Alastair J. , Marshall Charles R.
Published: December 2021

Background

Central auditory function is affected early in the course of Alzheimer’s disease, and may be useful as a prodromal disease marker. Speech‐in‐noise perception is a simple test of central auditory function.

Method

We used Speech Reception Threshold (SRT) as a measure of speech‐in‐noise perception in 160,905 healthy subjects in UK Biobank. We assessed odds ratios for incident Alzheimer’s disease by SRT quintile at a mean follow up of 10 years. In a subgroup of 37,082 healthy subjects with contemporaneous cognitive testing and brain imaging we assessed the relationships of SRT with cognitive performance and structural neuroanatomy using voxel‐based morphometry (VBM).

Result

Poorer (higher) SRT was associated with greater odds of incident Alzheimer’s disease (odds ratio for quintile 5 relative to quintile 1: 2.91 (95%CI 1.92‐4.57); p=0.000001). Worse SRT was associated with poorer cognitive performance in multiple domains. VBM revealed symmetrical grey matter correlates of SRT in a distributed network of auditory and speech perception areas, as well as medial temporal lobe structures.

Conclusion

Speech‐in‐noise perception is a simple non‐invasive assay of cognition, brain structure and risk of incident Alzheimer’s disease, and as such may be readily translatable as a cost‐effective tool for dementia risk stratification at large‐scale.
Utilization of a novel digital neuropsychological assessment Suite in patients with Alzheimer’s disease and cognitive healthy controls: A preliminary investigation
Authors: Myers Jennifer Rae , Ozaki Satoshi , Madero Erica N. , Harrison John E , Mak‐McCully Rachel , Onguchi Kaori , Gray Michelle , Glenn Jordan M.
Published: December 2021

Background

Globally, the prevalence of Alzheimer’s disease is expected to triple by 2050. Additionally, as COVID‐19 has accelerated the urgency for remote neuropsychological assessment, the development of easily accessible and valid remote methods of assessments are critical for continued monitoring of cognitive health. In response to this clinical and scientific need, we investigate the use of the Neurotrack assessment suite as a remote digital cognitive assessment platform.

Method

As part of an ongoing study, 9 patients diagnosed with AD (Mean age = 75.6, 55% female) and 9 cognitively healthy controls (Mean age = 75.6, 44% female) were assessed using three exams from the Neurotrack assessment suite which were designed to assess 1) processing speed, 2) associative learning and 3) associative and recognition memory. Independent samples t‐tests were conducted to examine differences in exams scores between the two groups.

Results

There were significant differences observed in processing speed (p=.004), associative learning (p=.001), and associative memory performance (p=.03) between patients with AD and cognitive healthy controls. There was no difference in recognition memory (p=.47).

Conclusion

The Neurotrack Assessment Suite appears to be a promising method for remote cognitive testing. Further investigation of the efficacy of this platform as a valid and easily accessible assessment tool is currently underway.
Lipid peroxidation mediates the relationship between cardiopulmonary fitness and depressive symptoms in people with coronary artery disease
Authors: Feng Vivian , Tumati Shankar , Wang RuoDing , Bawa Kritleen Kaur , Gallagher Damien , Herrmann Nathan , Andreazza Ana C. , Swardfager Walter , Marzolini Susan , Oh Paul I. , Lanctôt Krista L.
Published: December 2021

Background

Emerging evidence suggests that poor cardiorespiratory fitness levels are related to greater depressive symptoms. In those with coronary artery disease (CAD) depressive symptoms are common and are associated with an increased risk of mortality. Exercise intervention is suggested to have positive effects on depressive symptoms and counteract oxidative stress (OS) in the body. However, a mechanistic link between cardiorespiratory fitness (CRF) and depressive symptoms has not been identified in CAD individuals. We aim to investigate if OS explains the relationship between poor cardiorespiratory fitness and higher depressive symptoms in CAD individuals.

Method

CAD participants were recruited and OS was measured via serum lipid peroxidation marker 8‐isoprostane (8‐ISO), lipid hydroperoxides (LPH), and 4‐hydroxyneoneal (4‐HNE). CRF was assessed by peak oxygen uptake (VO2peak) and depressive symptoms measured via Center for Epidemiological Studies‐Depression (CES‐D) scale. Analyses were controlled for age, hypertension, hypercholesterolemia, and antidepressant use. Mediation effects of OS markers on the relationship between CRF and depressive symptoms were tested. A bias‐corrected inferential bootstrapping with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect.

Result

Among CAD individuals (n=224), lower VO2peak was associated with higher 8‐ISO (β=0.31, p<0.001) and greater depressive symptoms (β=‐0.143, p=0.038). LPH (B=‐0.172 p=0.017) was associated with greater CES‐D score, but not VO2peak levels (B=‐0.122, p=0.109), when controlling for the same covariates. 4‐HNE was not a significant predictor of CES‐D scores (B=0.059, p=0.372) or VO2peak levels (B=‐0.052, p=0.440). 8‐ISO mediated the relationship between VO2peak (β=0.02, p=0.01) and CES‐D (β=7.13, p=0.001), and LPH did not (‐0.0098, 95% CI [‐0.0314, 0.0042]). Bootstrapping produced a significant unstandardized indirect effect for 8‐ISO (β=‐0.20, SE=0.05, 95% CI=‐0.32, ‐0.01).

Conclusion

In those with CAD, poor CRF and greater OS levels were associated with higher depressive symptoms, and this relationship was mediated by 8‐ISO, but not LPH or 4‐HNE. These findings provide greater understanding of the mechanistic reasoning for the link between poor CRF and depressive symptoms.
Reporting amyloid beta levels via bioluminescence imaging with amyloid reservoirs
Authors: Yang Jing , Ding Weihua , Zhu Biyue , Shen Shiqian , Ran Chongzhao
Published: December 2021

Background

Bioluminescence imaging has changed daily practice in preclinical research of cancers and other diseases in the last decades; however, it has been rarely applied in preclinical research of Alzheimer’s disease (AD).

Method

In this report, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Ab) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Ab aggregates and plaques. We further speculated that the Ab species have the reservoir capacity to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Abs.

Results

Our hypotheses have been validated via in vitro tests, mimic phantom imaging, and in vivo imaging using transgenic AD mice that were virally transduced with aka Luciferase (AkaLuc), a new luciferase that generates bioluminescence in the near infrared window. As expected, compared to the control group, we observed that the Ab group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and therapeutic effectiveness of avagacestat, a well‐studied gamma‐secretase inhibitor.

Conclusion

Our approach can be easily implanted into daily imaging experiments. We believe that our method has tremendous potential to change daily practice of preclinical AD research.
Hearing loss in older adults interacts with sex and APOE4 to lower resting‐state functional connectivity
Authors: Fitzhugh Megan C , Pa Judy
Published: December 2021

Background

Hearing loss was recently identified as a modifiable risk factor for dementia. However, investigations have yet to evaluate whether hearing loss may interact with other risk factors of dementia, such as female sex and APOE4 allele. The goal of this study was to explore the associations between hearing loss, female sex, and APOE4 on functional connectivity.

Method

Resting‐state fMRI functional connectivity in 1,000 participants (61.98±7.41 years, 50% female, 50% APOE4 carriers) from the UK Biobank was computed between bilateral planum temporale ROIs (auditory seed regions) and the 1) default mode (DMN), 2) frontoparietal (FPN), and 3) cingulo‐opercular (CON) network ROIs (target regions). Hearing was measured with a speech in noise reception task, which was used to split participants into better performing ear groups (better left ear (56%): ‐5.97±1.50dB; better right ear (44%): ‐6.07±.1.55dB), in which higher scores indicate poorer hearing. ANCOVA models with FDR corrections were used to examine associations of functional connectivity and left and right ear hearing measures, controlling for age. Interactions with sex and APOE4 status were examined, followed by stratified models for sex and APOE4.

Result

Left ear hearing was poorer in females compared to males; this sex difference was also observed within APOE4 carriers. Right ear hearing did not differ between groups. Main effects of sex on functional connectivity showed that females generally have lower connectivity than males; no main effects of APOE4 were observed. Stratified analyses showed that female APOE4 carriers with poorer left ear hearing showed lower functional connectivity between left planum temporale and ROIs of the DMN and CON. Similar results were found for functional connectivity from right planum temporale. No significant associations were found for female noncarriers, male carriers and noncarriers, nor for right ear hearing.

Conclusion

Hearing loss is associated with lower functional connectivity in females who are APOE4 carriers. Lower functional connectivity was observed between auditory processing areas and networks associated with episodic memory, working memory, and attention. These results support that a possible mechanistic underpinning for why hearing loss increases risk for dementia may be due to altered connectivity to higher‐order cognitive networks, particularly for females who are APOE4 carriers.
Microglia activation predicts tau positivity beyond Aβ in Alzheimer’s disease
Authors: Ottoy Julie , Bezgin Gleb , Savard Mélissa , Mathotaarachchi Sulantha , Pascoal Tharick A. , Chamoun Mira , Soucy Jean‐Paul , Gauthier Serge , Rosa‐Neto Pedro
Published: December 2021

Background

Deposition of amyloid‐beta (Aβ) plaques and hyperphosphorylated tau are known hallmarks of Alzheimer’s disease (AD). In addition, neuroinflammation or microglia activation plays a role in Alzheimer’s pathophysiology and may be a potential driver of abnormal tau deposition. This study demonstrated the important brain regions where microglia activation, in addition to Aβ, is driving tau positivity in AD.

Method

120 participants from the TRIAD cohort underwent 18F‐AZD4694 amyloid‐PET, 18F‐MK620 tau‐PET, and 11C‐PBR28 neuroinflammation‐PET. All images were normalized to the ADNI template and quantified as SUVR in 35 regions‐of‐interest using cerebellar gray as the reference region. ANCOVA was used to assess the differences in levels of microglia activation between tau‐positive (T+; n=38) vs. tau‐negative (T‐; n=82), corrected for age, sex, APOE‐e4, education, and global Aβ. Tau status was based on both visual rating with elevated uptake in Braak1and2 and quantitative cut‐off of 1.22. In addition, step‐wise logistic regression was conducted to predict T+ in three steps: 1) the covariates, i.e. age, sex, APOEε4, and education, 2) covariates + global Aβ, and 3) covariates + global Aβ + activated microglia in each of the 35 ROIs, corrected for multiple comparisons using FDR. Our prediction model was trained based on a randomly selected 70%/30% training/test set. In order to investigate the stability of our model, this procedure was repeated 500 times.

Result

Levels of microglia activation were significantly increased in T+ compared to T‐ in the posterior cingulate (p=0.0001), middle (p=0.02) and inferior (p=0.0005) temporal, fusiform (p=0.0004), and orbitofrontal cortex (p=0.005). Based on logistic regression and a likelihood‐ratio test between each step, we found that the ‘covariates + global Aβ model’ performed significantly better in predicting T+ than the ‘covariates‐only’ model (χ2(1)=72.64, p<0.0001). In the 3‐step model, the addition of activated microglia showed a significantly improvement of the model’s performance to predict T+, particularly the activated microglia in the hippocampus (p=0.001), middle (p=0.006) and inferior (p=0.001) temporal, and fusiform (p=0.001) cortex. Receiver operating characteristic curves (ROC) and AUCs are shown in Fig 1.

Conclusion

Our study demonstrated that activated microglia in the Braak2 to Braak4 regions play an important role in predicting tau positivity in addition to Aβ.
The link between blood‐based biomarkers and mild cognitive impairment and Alzheimer's disease in a Panamanian sample
Authors: Oviedo Diana C. , Villarreal Alcibiades E. , Rangel Giselle , Carreira Maria B. , Perez‐Lao Ambar R. , Rodriguez Sofía A. , Posada Camilo , Britton Gabrielle B.
Published: December 2021

Background

Studies on blood‐based biomarkers associated with age‐related cognitive impairment are key to improve intervention mechanisms and delay the expression of symptoms. The objective of this study was to assess the relationship between blood‐based biomarkers and mild cognitive impairment (MCI) and AD in a sample of elderly Panamanians enrolled from an outpatient geriatric service.

Method

A descriptive, cross‐sectional, observational study was conducted. Participants were 84 Panamanians (controls, n=41; MCI=32; and AD=11). They were assessed with MMSE and Clock Test. Non‐fasting blood samples were collected to genotype for ApoE4 and to determine a blood‐based biomarker profile.

Result

CRP levels among AD participants were significantly increased relative to MCI participants (p < 0.05). A2M levels in AD participants were significantly increased compared to normal controls (p < 0.05). SAA levels in AD participants were significantly increased when compared to MCI participants (p < 0.05).

Conclusion

These results show that in the AD group CRP, A2M and SAA are significantly increased. The link between MCI and AD and inflammatory markers can produce an accurate tool that can aid in early diagnosis of AD.
Semantic clustering and memory in the everyday problem‐solving of mild cognitive impairment subtypes
Authors: Nayares Claudia , Bailey Makayla , Jimenez Celine , Balakid Jannine , Lent David D , Alving Loren , Woo Ellen
Published: December 2021

Background

Semantic clustering, which involves grouping words into categories, is an efficient memory strategy that enhances the recall of older adults. Changes in the semantic network are a hallmark of Alzheimer’s disease (AD). The associated decline in semantic clustering that has been observed, even in mild cognitive impairment (MCI), can affect the ability to compensate for memory difficulties. In this study, we investigated the roles of semantic clustering and memory in the everyday problem solving of MCI and its subtypes.

Method

Participants included 56 healthy older controls and 52 persons with MCI (n=26 amnestic MCI; n=36 non‐amnestic MCI). All participants were administered the California Verbal Learning Test‐II to assess semantic clustering and memory. The Everyday Problems Test (EPT) was also administered to assess problem‐solving skills involved in activities of daily living (ADLS; i.e., telephone use, shopping, meal preparation, housekeeping, transportation, health/medication use, and finances).

Result

Regression analyses indicated that immediate and delayed free recall predicted EPT scores in the control group, while only immediate free recall predicted EPT scores in the non‐amnestic MCI group. Semantic clustering was not predictive of EPT scores in any group. Further, memory and semantic clustering did not predict EPT scores in the amnestic MCI group.

Conclusion

Overall, we found that memory performance predicted everyday problem solving, while semantic clustering, an efficient memory strategy, did not. More specifically, memory predicted everyday problem solving only in those who did not exhibit objective memory deficits (i.e., healthy older controls and non‐amnestic MCI). This suggests that older adults engage intact memory skills to perform problem‐solving based ADLs. In contrast, those with memory deficits do not employ memory or memory strategies to perform these ADLs. This indicates that possibly training persons with MCI in compensatory strategies may benefit them in their everyday lives.
SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN (SUPERBRAIN) showed improvement in cognitive function mostly in individuals with nutritional improvement: Sub‐analysis of SUPERBRAIN results
Authors: Park Yoo Kyoung , Song Jae Eun , Hong Chang Hyung , Moon So Young , Jeong Jee Hyang , Park Hee Kyung , Na Hae Ri , Choi Seong Hye
Published: December 2021

Background

The MIND diet (Mediterranean‐DASH Intervention for Neurodegenerative Delay) is reported to be effective in preventing dementia. As the number of older adults with dementia in Korea increases, intervention programs suitable for older adults with dementia are needed. Therefore, we developed a Korean multi‐domain dementia prevention program including nutrition, exercise, cognitive training, vascular disease prevention and motivation.

Method

One‐hundred fifty three participants aged 60‐79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the FMI (Facility‐based intervention), HMI (Home‐based intervention) and the control group. The nutrition education program consisted of 10 classes during 24 weeks: the FMI received 7 group sessions and 3 1:1 sessions, the HMI received 4 group sessions and 3 1:1 sessions with 3 times homework sessions. The NQ‐E (Nutrition Quotient for Elderly) and the MNA (Mini Nutritional Assessment) were used to evaluate nutritional status. The RBANS (Repeatable Battery for Neuropsychological Status) and the CCI (Cognitive Complaint Interview) were used to evaluate cognitive function.

Result

A total of 136 people (36 males and 100 females) completed the program with an 11.1% dropout rate. The NQ‐E score (p=0.009) and the RBANS score (p=0.001) were significantly increased in the FMI (N=45) and HMI (N=49) compared to the control group (N=42) after the study. The changes in the MNA score and the CCI score did not differ significantly among groups. As a result of sub‐analysis with the changes in the NQ‐E score before and after the study, there was no significant difference in cognitive function indicators among three groups when there was no change or improvement in the NQ‐E score. On the other hand, for those whose NQ‐E score was improved, the RBANS scores of the FMI (N=32) and the HMI (N=37) were significantly increased compared to the control group (N=25) (FMI: 0wk 496.69 points, 24wk 510.41 points; HMI: 0wk 502.86 points, 24wk 519.86 points, p=0.024).

Conclusion

In conclusion, nutritional intervention focused on the MIND diet as a part of a multi‐domain intervention had an effect on improving the nutritional status and cognitive function score in the high‐risk group of dementia.
Cognitive health mediates the effect of hippocampal volume on COVID‐19‒related knowledge or anxiety change during the COVID‐19 pandemic
Authors: Kang Min Su , Ottoy Julie , Servaes Stijn , Lussier Firoza Z , Bezgin Gleb , Chamoun Mira , Stevenson Jenna , Bzdok Danilo , King Suzanne , Gauthier Serge , Rosa‐Neto Pedro
Published: December 2021

Background

Individuals with cognitive/memory impairments may be more vulnerable to COVID19 due to having poor knowledge of COVID19 and how to protect themselves under current policies. Here, we aimed to show cognitive/memory impairment is associated with less knowledge or less anxiety change related to COVID19. We hypothesized that the effect of hippocampal volume on COVID19‐related knowledge or anxiety change during the pandemic is mediated by cognitive health.

Method

A total of 247 participants (162 cognitively normal (CN) and 85 cognitively impaired (CI)) from the Montreal TRIAD cohort underwent a structural MRI and cognition and anxiety assessments using CDRSOB and GAD score, respectively before the COVID19 pandemic. During the first wave of COVID19, the participants were assessed for anxiety using GAD score and knowledge related to COVID19. Hippocampal volume was measured using Freesurfer, and the anxiety was evaluated as the rate of change in the GAD score: (follow‐up – baseline)/time difference. Then, the effect of hippocampal volume on the rate of change in the anxiety or knowledge on COVID19 was evaluated based on a mediation analysis with CDRSOB as a mediator, 2000 bootstrapping, and age, sex, education, and APOEe4 as covariates.

Result

The CI group showed significantly less knowledge of COVID19, or less anxiety change compared to the CN group, while hippocampal volume showed a significant association with knowledge of COVID19 or the rate of change in anxiety. Upon further examination, we revealed that the effect of hippocampal volume on COVID19 knowledge or the rate of change in anxiety was significantly mediated by cognitive health, indicated by CDRSOB (Figure 1).

Conclusion

Our finding highlights the poorer knowledge of COVID19 and related risks in individuals with cognitive/memory impairments; the CDRSOB, indicative of cognitive health, significantly mediated the effect of hippocampal volume on the rate of change in anxiety or knowledge on COVID19 in our cohort. This study urges for a more effective strategy and policy about informing and educating the individual with cognitive/memory impairment on COVID19 and related risks.
Behavioral and psychological symptoms of Alzheimer’s disease during the COVID‐19 pandemic in underserved settings
Authors: Castro‐Suarez Sheila , Failoc‐Rojas Virgilio E , del Castillo Rossana Cruz , Montesinos Rosa , Herrera‐Perez Eder , Custodio Nilton
Published: December 2021

Background

The behavioral and psychological symptoms of dementia (BPSD) are characterized by disturbances in perceptions, thought contents, moods, and behaviors. The causes for these symptoms are connected to factors related to the people with dementia (PWD), his/her caregivers, and environmental factors as well as the interrelationship between these three. Disruptions of routine due to confinements during the COVID‐19 pandemic has led to the onset/worsening of BPSD, thereby increasing distress levels in caregivers, and risks of self‐injury, hospitalization, and death for PWD. Our aim is to describe the onset/ worsening of BPSD during COVID‐19 pandemic confinement.

Method

This is a longitudinal study in patients and caregivers of people with Alzheimer’s disease from the Instituto Peruano de Neurociencias in Lima, Perú. A structured confinement interview was delivered to caregivers exploring how the caregiver's activities have been affected or modified by the confinement measures. All patients have neuropsychological, neuropsychiatric, and functional assessments performed six months before the onset of the confinement. BPSD was assessed using the neuropsychiatric inventory questionnaire (NPI).

Result

A total of 91 patients with Alzheimer’s disease and caregivers participated in the study. The average age of the patients was 73.4 years. Most patients had a CDR score of 0.5‐1. Caregivers reported that the pandemic affected their mood by 74%. Percentage of time spent caring increased from 15% to 25% (p<0.001).

Worsening and new onset of behavioral and psychological symptoms were reported. The NPI (Fig 1.) and ADCS_ADL scores increased significantly during quarantine from baseline (6.6 and 10, respectively) (p<0.001). Delusions (75%), sleep disorder (71.7%), and hallucinations were the most frequently reported worsening symptoms. Sleep disorder (71.1%), agitation (68.6%) and depression (53.3%) were the most frequently reported new symptoms (p<0.001) (Table 1). Profile of BPSD did not vary according to the CDR score.

Conclusion

Quarantine induces increases in behavioral and psychological symptoms in patients with early stages of Alzheimer’s disease. Caregivers spent more time with the patient with AD and their emotions were affected by the pandemic. We need to plan for strategies in order to address these needs.
Role of transcranial direct current stimulation (TDCS) intervention on resting state functional connectivity in early Alzheimer’s disease
Authors: Roy Ashika Anne , Joshi Himanshu , Havanur Setu , Rangarajan Subhashini K , Sreeraj Vanteemar S , Sinha Preeti , Narayanan Mariyappa , Janakiprasad Keshav K , Alladi Suvarna , Sinha Sanjib , Saini Jitender , PT Sivakumar , Varghese Mathew , Venkatasubramanian Ganesan , John John P
Published: December 2021

Background

Working memory and executive function deficits are the characteristic features of Mild Cognitive Impairment and mild Alzheimer’s Disease (mild AD). Studies exploring the alterations in working memory and executive functions show disrupted functional connectivity in Dorsolateral Pre Frontal Cortices (DLPFC) and Angular Gyrus (AG). Transcranial direct current stimulation (tDCS), by stimulating these brain regions, can alter resting‐state functional connectivity (rs‐FC) and has emerged as a safe and non‐invasive technique that has the potential to enhance neuroplasticity and cognitive improvement.

Method

We investigated the effect of anodal stimulation at the left DLPFC and cathode placed at the right supra‐orbital area to observe the rsFC changes in patients with MCI and mild AD (n=12; Age=67.58 ± 8.59 years, Gender ratio 1:1, formal years of education= 14.58±3.55 years, Hindi mental Status examination=26.91±3.1), who attended the outpatient services of Geriatric Clinic and Services, after due approval from institute ethics committee NIMHANS. The resting‐state functional magnetic resonance imaging (rsfMRI) acquisitions were performed before and after the ten sessions of tDCS, each session lasting 20 minutes. Investigations were performed on subregions of DLPFC (left Superior Frontal Gyrus (LSFG), Right SFG, left Middle Frontal Gyrus (LMFG) and Right MFG) and Angular Gyrus (Right Angular Gyrus (RAG) and Left AG), chosen a priori as seeds for the seed based FC (sbFC) analysis after correcting for the influences of age and gender using CONN 18b toolbox. Spherical masks of size 5 mm diameter were also created for the above‐mentioned seeds.

Result

The pre‐post tDCS comparisons of sbFC showed significant (FDR; p<0.05) reduction of rsFC in patients with MCI and mild AD at right supramarginal gyrus, right angular gyrus, right frontal pole (for Seed‐RAG, Voxel‐ whole brain), supramarginal gyrus (for Seed‐RAG, Voxel‐ RAG), and Middle Temporal gyrus, left Temporo‐Occipital part (for Seed‐ RSFG, Voxel‐ whole brain) as shown in Figure 1 a, b, and c respectively (Refer Table 1).

Conclusion

The results support that anodal stimulation using tDCS at left DLPFC may lead to the reduction of aberrantly increased functional connectivity between brain regions involved in working memory and executive functions in MCI and mild AD.
A novel antibody‐free mass spectrometry panel of CSF biomarkers for synaptic dysfunction
Authors: Nilsson Johanna , Cousins Katheryn A.Q. , Gobom Johan , Portelius Erik , Chen‐Plotkin Alice , Shaw Les M. , Grossman Murray , Trojanowski John Q. , Zetterberg Henrik , Blennow Kaj , Brinkmalm Ann
Published: December 2021

Background

One of the earliest events and the best correlate to cognitive decline in neurodegenerative diseases, such as Alzheimer’s disease (AD), is synaptic dysfunction and degeneration. Thus, identifying and validating new biomarkers capable of quantifying synaptic degeneration for use as prognostic biomarkers would be very valuable for diagnostic purposes. We have developed a novel assay in which 17 synaptic proteins are simultaneously quantified in cerebrospinal fluid (CSF). The proteins in the panel include but are not limited to: synucleins, neuronal pentraxins, SNARE proteins and neurogranin. In a pilot study, we previously observed that several of these proteins may serve as synaptic biomarkers for AD. In this follow‐up study we aimed to confirm our previous results as well as expand to other neurodegenerative disease such as frontotemporal lobar degeneration (FTLD) and disorders with α‐synuclein pathology.

Method

Sample preparation of 100 µL CSF samples was performed in a consecutive three‐step process constituting of stable isotope labeled peptide standards addition, tryptic digestion followed by purification by solid‐phase extraction. For quantification was micro‐high‐performance liquid chromatography‐mass‐spectrometry (triple quadrupole) used. A cross‐sectional study including controls (n=47), AD (n=63), FTLD (n=103) and α‐synuclein patients (n=22) was performed.

Result

In the study the most notable results were found for 14‐3‐3 zeta/delta, beta‐synuclein and the pentraxins. All three pentraxins (1, 2 and the receptor) were decreased compared to controls across all groups, while 14‐3‐3 zeta/delta was increased. Further, beta‐synuclein was seemingly specifically altered (increased) between controls and AD, while no difference was observed between controls and FTLD, and α‐synuclein patients.

Conclusion

We have successfully developed a panel of novel CSF biomarkers for synaptic dysfunction. We present results suggesting that several synaptic proteins potentially could be used as biomarkers for synaptic dysfunction and degeneration in not only AD but also other neurodegenerative diseases such as FTLD and α‐synuclein pathologies.
The association between sleep and cognitive pre‐frailty in community‐dwelling older adults: A two‐year cohort study
Authors: Huang Tzu‐Hsin , Chen Yen‐Ching , Chen Ta‐Fu , Yeh Su‐Ling , Chiou Jeng‐Min , Chen Jen‐Hau
Published: December 2021

Background

Sleep has been related to cognition and frailty, respectively. Cognitive frailty, the co‐existence of mild cognitive impairment (MCI) and physical frailty, has been proposed in 2013 and its relation with sleep remains unclear. To predict cognitive frailty in the preclinical stage, this study aimed to explore the relationship between sleep and cognitive pre‐frailty in non‐demented older adults.

Method

This study is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research. After exclusion of participants with specific conditions and loss to follow‐up, 324 older adults from the senior health checkup program of National Taiwan University Hospital were included at baseline (2015‐2017). Outcome of this study was the coexistence of MCI and pre‐frailty (cognitive pre‐frailty) and were assessed at baseline and two‐year follow‐up (2017‐2019). Global and domain‐specific cognition were assessed by Taiwanese version of Montreal Cognitive Assessment and a battery of neuropsychological tests, respectively. Pre‐frailty was defined as the existence of one or two out of five conditions using modified Fried’s frailty phenotype. Sleep variables was available at baseline, which included global sleep quality [assessed by Pittsburgh Sleep Quality Index (PSQI), score range: 0‐21)], sleep duration (in hours), and daytime sleepiness (assessed by Epworth Sleepiness Scale, ESS, score range: 0‐24). Generalized linear mixed model was utilized to assess the association between sleep and cognitive pre‐frailty over 2 years adjusting for age, sex, years of education and other important covariates.

Result

Participants’ mean age was 75.2 years at baseline. Prevalence of cognitive pre‐frailty was 1.85% at baseline and 2.55% at two‐year follow‐up. Instead of a linear relationship, we found a non‐linear association between sleep and cognition. When mean PSQI score and mean sleep duration deviated from the corresponding sample mean (PSQI score: 6.3; sleep duration: 6.2 hours), the severity of cognitive pre‐frailty increased [quadratic PSQI score: adjusted odds ratio (aOR)=1.02, 95% confidence interval (CI)=0.01‐0.04; quadratic sleep duration: aOR=1.15, 95% CI=0.04‐0.23]. No significant association was found between daytime sleepiness and cognitive pre‐frailty.

Conclusion

This study found a nonlinear association of global sleep quality and sleep duration with cognitive pre‐frailty over two years in the community‐dwelling older adults.
Gender minority BIPOC adults in the U.S. report greater subjective cognitive decline
Authors: Cicero Ethan , Wharton Whitney , Flatt Jason D
Published: December 2021

Background

There is limited research investigating risk of cognitive impairment and Alzheimer’s disease and related dementia (ADRD) among gender minority (GM) adults (i.e. transgender, non‐binary). To‐date, no study has examined these cognitive challenges among GM who identify as Black, Indigenous, or People of Color (BIPOC). The health and social inequities experienced by GM BIPOC are linked to an increased risk of cognitive impairment in cisgender (CG) adults. Subjective cognitive decline (SCD), a self‐reported experience of worsening memory or thinking, may be one of the first clinical manifestations of ADRD.

Method

2015‐2019 Behavioral Risk Factor Surveillance System data, representing 33 states that assessed SCD and gender identity, were used to create a 1:4 matched analytic sample (1GM matched to 2CG males and 2CG females on U.S. state, age, race) to examine SCD among GM BIPOC (N=129), GM White (N=324), CG BIPOC (N=513), and CG White (N=1296) adults aged 45‐65. Logistic regression and adjusted odds ratios were used to determine SCD and SCD‐associated functional limitations prevalences and test for differences in prevalence and demographic characteristics.

Result

SCD prevalence was highest among GM BIPOC (26.36%) and GM White (17.90%), followed by CG BIPOC (12.28%) and CG White (9.72%). The odds of SCD were 1.64‐3.32 times higher in GM BIPOC relative to the other groups. There were no differences in prevalence of SCD‐associated limitations. After accounting for demographic characteristics, GM BIPOC adults were nearly twice as likely to report SCD when compared to both CG BIPOC (CL: 1.06–3.02, P=0.0283) and CG White adults (95% CL: 1.22–3.20, P=0.0059).

Conclusion

Past research highlights that BIPOC adults suffer from ADRD at higher rates than Whites. When considering the intersection of GM status and identifying as BIPOC, we found that SCD prevalence was highest among GM BIPOC and GM BIPOC had higher odds of SCD when compared to CG BIPOC. Additional studies are needed to understand correlates and modifiable risk factors of cognitive impairment among GM BIPOC adults. This understanding is necessary for identifying GM adults at higher risk for cognitive impairment, reducing ADRD risk, and improving care and quality of life for this understudied population.
Living with and caring for: Experiences of dementia within LGBTQ2+ communities in Canada
Authors: Stinchcombe Arne
Published: December 2021

Background

With an aging Canadian population, the number of people living with Alzheimer’s disease and related dementias (ADRD) is expanding. Older members of lesbian, gay, bisexual, transgender, queer, and two‐spirit (LGBTQ2+) communities have expressed distinct concerns related to developing and living with dementia, often stemming from their sexual and/or gender minority identities. There continue to be gaps in our knowledge about LGBTQ2+ persons with dementia and caregivers. The purpose of this study was to examine the lived experiences of LGBTQ2+ persons with dementia and LGBTQ2+ caregivers.

Method

In‐depth semi‐structured interviews with persons with dementia and caregivers (n=7) were conducted. Data were analyzed using a constructivist grounded theory approach.

Result

Through analysis, findings identified were related to LGBTQ2+ identities, adaptation, relationships, and stigma.

Conclusion

The findings highlight the importance of inclusive policy and practice approaches to support LGBTQ2+ persons with dementia and caregivers.