bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurological and cognitive impairment in COVID‐19: clinical characterization andepidemiological
Authors: Júnior José Wagner Leonel Tavares , Neto Pedro Braga , Neto Manoel Alves Sobreira , MONTENEGRO RAQUEL CARVALHO , MOREIRA CAROLINE DE FÁTIMA AQUINO , de Oliveira Lais Lacerda Brasil , da Silva Jean Breno Silveira , Gomes Carmem Meyve Pereira , Gaspar Safira de Brito , Cunha Letícia Chaves Vieira , Sousa Artur Victor Menezes , Feitosa Werbety Lucas Queiroz , Oliveira Danilo Nunes
Published: June 2023

Background

COVID‐19 neurological manifestations were demonstrated during the pandemic, including cognitive impairment. Objectives: To determine the prevalence of cognitive and behavioral complaints (such as dementia, MCI or SCD) in a outpatient sample with recent SARS‐COV2 infection. Specific: Evaluate the association of cognitive impairment with the presence of the polymorphism found in the APOE gene and with respiratory disease

Method

Observational, longitudinal, prospective clinical study. Inclusion criteria: patients with confirmed Covid‐19. Patients are evaluated in an outpatient clinic. They are evaluated through a standardized attendance record, with somatic and cognitive neurological assessment. Cognitive assessment involves the application of cognitive (ACER, MMSE and CDR), functional (Pfeffer) and psychiatric (GDS or Beck) screening instruments, in addition to subsequent extensive neuropsychological assessment. In addition, APOE polymorphism is analysed.

Results

To date, 200 patients were evaluated. The average age is 46.5 years, with 65.4% female, 79.16% with 8 or more years of schooling, in addition to 57.5% of the sample with cognitive complaints.

Conclusions

The results so far in our study demonstrate that cognitive complaints are frequent in patients even in the chronic phase of the disease.
MBI‐apathy, ApoEɛ2, and risk for Alzheimer disease dementia
Authors: Vellone Daniella A , Ghahremani Maryam , Ismail Zahinoor
Published: June 2023

Background

Apathy, characterized by decreased interest, initiative, and emotional reactivity, is amongst the most common neuropsychiatric symptoms in dementia. However, apathy can emerge before dementia and constitutes a domain of mild behavioral impairment (MBI), an at‐risk state for incident cognitive decline and dementia. MBI‐apathy is the de novo emergence of persistent apathy in dementia‐free older adults and may be a driving factor in dementia risk conferred by MBI. Apolipoprotein E (ApoE) is a risk marker for Alzheimer disease (AD) dementia. Compared to ApoEɛ3 homozygotes, ApoEɛ2 carriers are 40% less likely to develop AD while ApoEɛ4 carriers are 3.2‐14.9 times more likely. We investigated the association between MBI‐apathy, ApoE, and incident dementia. We hypothesized that ɛ2 would have protective effects for MBI‐apathy associated risk, compared to ɛ3 and ɛ4.

Method

Dementia‐free participants in the National Alzheimer’s Coordinating Centre were stratified as MBI‐apathy and no‐NPS until dementia diagnosis, based on Neuropsychiatric Inventory Questionnaire scores at 2 consecutive visits. ApoE genotypes were categorized by ɛ2 (ɛ2/ɛ2, ɛ2/ɛ3), ɛ3 (ɛ3/ɛ3), and ɛ4 (ɛ4/ɛ3, ɛ4/ɛ4) alleles. Group characteristics were contrasted to determine covariate inclusion in regression modelling. Cox regressions assessed risk of incident dementia and included an interaction term for MBI‐apathy and ApoE allele.

Results

Of the 3,644 participants (3,022 Normal‐Cognition); 314 had MBI‐apathy (Table 1). Significant main effects were found for MBI‐apathy and incident dementia (HR:2.51, 95% CI:1.99‐3.17, p<0.001) as well as interaction effects with ApoE. In MBI‐apathy (ɛ3 as reference), the ɛ2 group had a 60% lower dementia risk (adjusted HR:0.40, 95% CI:0.19‐0.85) while ɛ4 had a 16% higher risk (adjusted HR:1.16, 95% CI:0.80‐1.69) (Figure 1). Of the 125 participants with apathy who progressed to dementia, 80.8% had AD. In the no‐NPS group (ɛ3 as reference), ɛ2 individuals had a 17% lower dementia risk (adjusted HR:0.83, 95% CI:0.52‐1.33) while ɛ4 individuals had a 177% higher risk (adjusted HR:2.77, 95% CI:2.13‐3.59) (Figure 2).

Conclusion

To our knowledge, this is the first study examining the relationship between MBI‐apathy and ApoE status in determining dementia risk. Results suggest that ApoE modifies the association between MBI‐apathy and incident dementia with the ɛ2 allele acting as a protective factor.
Bidirectional Mendelian randomization analyses reveal APOE status mediates the effects of statin medications on Alzheimer’s disease
Authors: Guo Xingzhi , Chong Li , Zhang Xin , Li Rui
Published: June 2023

Background

There is currently no unanimous conclusion on the statin medications and Alzheimer’s disease (AD) risk, which has long been one of the most concerns in lipid‐lowering and anti‐atherosclerosis treatment. We performed a bidirectional Mendelian Randomization (MR) to evaluate whether there were causal links between statin medications and AD.

Method

Single nucleotide polymorphisms (SNPs) identified from genome‐wide association studies (GWAS) were used as instrumental variables. One GWAS of statin medications (N = 462,933) and AD (N = 63,926) with summary statistics available was included in the MR analysis. All statistical analyses were conducted using the TwoSampleMR package with default parameters. Inverse variance weighted (IVW) was used as the primary method to calculate the causal estimates (β), accompanied by two complement methods, MR‐Egger and weighted median. Pleiotropic effects and heterogeneity driving causal association were also assessed.

Result

IVW results showed that genetically predicted use of statins was causally associated with increased risk of AD (atorvastatin: β = 33.67, P = 0.048; simvastatin: β = 4.88, P = 0.044). However, after removing SNPs inside the apolipoprotein E (APOE) gene region (CHR19:45,111,942‐45,711,941 based on GRCh37/hg19), the causal links of statin medications on AD disappeared (Figure 1A). Two SNPs, rs429358 (C;C) and rs7412 (C;C) known as APOE4 mainly contributed to the controversial data involved in use of statins and AD risk. The results of reverse causal analysis showed that patients with AD tended to have a higher exposure to statins (atorvastatin: β = 0.005, P = 0.001; simvastatin: β = 0.012, P = 0.004). Consistently, when discarding the SNPs within the APOE gene region, no relationship was found between diagnosis of AD and statins exposure (Figure 1B). The directional horizontal pleiotropy and heterogeneities found in MR‐PRESSO global and MR‐Egger regression test were largely disappeared after excluding SNPs inside APOE cluster region.

Conclusion

Our results suggested that the inconsistent association between statins use and AD risk observed in previous observational investigations might be mainly attributed to various APOE status (APOE2, APOE3, and APOE4). Thus, it reminds clinicians that statins can be used with confidence in lipid‐lowering and anti‐atherosclerosis and are unlikely to affect AD risk.
Detecting age‐dependent deterioration of spatial working memory with a virtual water maze paradigm in human subjects
Authors: Wang Eileen Han‐Jie , Lai Frank Ho‐yin , Shiu Alice Tsz‐Yan , Wong Hui Yan , Leung Sharifa Wing‐Man , Chan Daniel Ting Hoi , Yee Benjamin K
Published: June 2023

Background

Virtual‐Morris Water Maze (V‐MWM) has been developed to assess potential hippocampal‐dependent memory decline. Previous attempts showed the V‐MWM was sensitive in detecting age‐related reference memory decline, but our pilot study indicated that elderly often could not complete the tasks within 60s. Therefore, we have investigated further the use of a spatial working memory paradigm to evaluate one‐trial learning task allowing for up to 120s per trial.

Methods

Three age groups were recruited from the community with a cross‐sectional design. The Young Adult (YA,n = 22), Young Elderly (YE,n = 30) and older elderly (OE,n = 19) groups defined according to the subjects’ age in years: 18‐45, 60‐69, and 70 or above, respectively. The V‐MWM was programmed using MazeWaker. Subjects navigated in a 3D circular arena, defined by uniform walls and presented on a 14‐inch screen using an arrow key. Eight distal 3D‐cues located outside the arena. A total of 8 possible locations assigned randomly to every two consecutive trials. The two trials were separated by 5s or interspersed by a comic strip for 15s. The target become visible after 120s. Working memory was indexed by more efficient navigation from trial‐1 to trial‐2 in terms of latency or path‐length, indexed by the ratio: T2/(T1+T2) and subjected to a 3×2×3 (AgexInterference typesxLocations) ANOVAs. Two 60s‐nonrevealing probe tests were conducted on trials 8th and 16th. Percent path‐length near the 8 possible target‐zones using separate 2×2×8 (Age groupsxInterference typesxTarget‐zones) ANOVAs.

Results

The YA group outperformed both the YE and OE groups (F(2,68) = 8.17, p = .001), but no significant group by interference interaction was revealed. However, the 15s‐interference tended to increase the latency in both YA and YE groups (F(1,68) = 9.05, p<.005). An overall preference for the target zone was identified in both percent time and path‐length (F(7,62) = 6.03 and 8.71, respectively, p<.001), together with a significant Age x Zones interaction (F(14,126) = 8.71, p<.001) indicative of reduce target zone preference in the OE relative to YA, with YE performing at an intermediate level.

Conclusions

ur V‐MWM working test was sensitive to detect age‐related visual‐spatial working memory deterioration, but our interference procedures were insufficient to reduce working memory performance in all groups. Alternative interference may be considered in the future.
Biological risk factors for dementia in India
Authors: Crimmins Eileen M. , Farina Mateo , Wu Qiao , Kim Jung Ki , Zhang Xinyao
Published: June 2023

Background

Many clinical biomarkers have been associated with dementia. This paper uses a novel data set from an understudied population – a national sample of older Indians ‐ to assess the relative importance of 41 biomarkers using a variety of approaches. The value of these data is the extensiveness of the biomarker collection, the validated classification of dementia, and the uniqueness of the population with low average education. Many approaches to both summarizing and reducing data complexity have been suggested. Some of these are based on theory about biological mechanisms and some are agnostic and based on machine‐learning approaches. The results are informative for others collecting and analyzing biomarker data in population samples.

Method

We use 6 approaches to assessing the value of the biomarkers in explaining variance in dementia diagnosis and cognitive functioning – some traditional social science approaches and some based on machine learning. The aim of the different approaches is to determine how to best characterize the influence of biology as well as how to trim and combine the data. The five approaches to measuring biological risk: 41 individual biomarkers; identification of subsets of biomarkers with elastic net; support vector machine learning; factors developed with factor analysis; a principal components approach; and a factor classification based on a theoretical approach.

Results

Results indicate if the aim is explain variance in dementia, all the biomarkers or a reduced set of biomarkers identified by elastic net do the best job at explaining variability. However, biological markers chosen as most important do not fit well our understanding of biological mechanisms.

Conclusion

If the aim is understanding the relative importance of biological systems, traditional social science approaches, e.g. the factor analysis and principal components approach, allow better understanding and interpretation of the biomarkers associated with cognitive performance.
Behavioral interventions for persons with mild cognitive impairment: Longitudinal effect on partners with low adjustment
Authors: Ying Gelan , Chandler Melanie , Shandera‐Ochsner Anne , Smith Glenn E. , McAlister Courtney B. , Locke Dona E.
Published: June 2023

Background

Partners of persons with mild cognitive impairment (pwMCI) show increased rates of depression and other mental health problems compared to the general population. While dyadic behavioral interventions such as cognitive rehabilitation have shown beneficial effects in reducing caregiver burden, research to date lacks consistent outcome measures and rarely focuses on distressed partners. Therefore, this study explored the longitudinal effect of the Healthy Action to Benefit Independence & Thinking® (HABIT) program on partners with relatively low initial adjustment level. We hypothesized that the HABIT program would improve partner adjustment in those who were distressed.

Method

Data from 322 pwMCI and partners were utilized from the HABIT IRB research registry. Among them, 240 completed HABIT while 82 served as an untreated control group. Consistent with our previous exploratory factor analysis, a composite partner adjustment score was calculated using the Center for Epidemiologic Studies Depression scale (CES‐D), the REACH Anxiety Inventory Form, and the Quality of Life scale for adults with Alzheimer’s Disease (QOL‐AD). We included partners with an adjustment score below the median of each group to focus on partners with low levels of baseline adjustment. Latent growth curve models were conducted at baseline, 3‐month, 6‐month, and 1‐year follow‐ups to investigate the trajectories of partner adjustment level.

Result

In the low adjustment subsample, no between group difference was found at baseline. An overall improvement in partner adjustment scores was observed only in the treatment group (b = 5.00, p<.001). The slope of change was larger (b = 3.75, p = .016) in the treatment group, indicating a faster improvement in adjustment level in HABIT partners with marginally lower baseline and higher follow‐up scores. This difference in the improvement rates was most evident at the 3‐month follow‐up (t(1, 94) = ‐2.63, p = .010) and gradually reduced in subsequent visits.

Conclusion

In partners of those with MCI who have low levels of emotional adjustment, behavioral interventions like HABIT can be beneficial in accelerating improvement in their overall adjustment level and facilitate adaptation to their loved ones’ MCI symptoms compared to untreated controls. Techniques taught in dyadic interventions may serve as protective factors for mental health problems in primary caregivers of pwMCI.
Lateral temporal atrophy is a better visual scale to predict MMSE score than hippocampal atrophy in Alzheimer’s disease: A retrospective cross‐sectional study
Authors: Nguyen Khang Vinh , Tong Trang Mai , Pham Trung Thanh , Tran Son The , Nguyen Truc Thanh Tran , Tran Thang Cong
Published: June 2023

Background

Mini‐Mental State Exam (MMSE) is helpful in the cognitive evaluation and staging of Alzheimer patients (AD), but its score could be affected by acute medical conditions, depression, or anxiety. Conversely, head magnetic resonance imaging (MRI) is an independent diagnostic tool to evaluate specific cerebral pathology in AD patients. Many studies have investigated the correlation between head MRI visual scales such as hippocampal atrophy and baseline MMSE to aid in the diagnosis of AD. However, there has not been a study that evaluates the correlation between a comprehensive head MRI visual scale with baseline MMSE in AD patients.

Method

We retrospectively collected records of outpatients diagnosed as probable AD according to DSM V criteria in two dementia wards. Patients with age of onset before 65 years old were considered early‐onset AD patients. The comprehensive visual rating scale (CVRS) was used to semiquantitative structural lesions, including hippocampal, cortical, subcortical atrophy, and small vessel disease. The relationship between MRI lesions and baseline MMSE was evaluated using Bayesian model averaging (BMA) to control confounders. Data analysis was done using R‐4.0.3.

Result

We collected 65 AD patients with 21 (32.31%) early‐onset AD. Lateral temporal atrophy, level of education, and late age‐onset were the strongest independent predictors of baseline MMSE, while other structural lesions were not significant in the BMA model. Furthermore, hippocampal atrophy was only correlated with delayed recall, while temporal atrophy was correlated with orientations, attentions, language, and visual‐spatial.

Conclusion

Our study suggests that the lateral temporal atrophy correlates more with the baseline MMSE score in patients with AD than the hippocampal atrophy.
Fecal microbiota transplant can improve cognition in patients with cognitive decline and Clostridioides difficile infection
Authors: Choi Seong Hye , Park Soo‐Hyun , Lee Jung‐Hwan , Shin Jongbeom , Im Jae Hyoung , Kwon Kye Sook
Published: June 2023

Background

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline.

Method

The study included 10 patients (age range, 63‐90 years; female, 80%) with dementia and severe CDI who were evaluated using cognitive function tests (Mini‐Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR‐SB] score) and stool PCR before and after FMT. Cognitive function test was performed one month before FMT and one month after FMT. The patients’ fecal samples were analyzed to determine the composition of their gut microbiota before FMT and 3 weeks after FMT to compare the microbiota composition.

Result

Ten patients receiving FMT showed improvements in clinical symptoms and cognitive functions. The MMSE score pre‐FMT was 10.00 (Median, 7.00 – 14.00 interquartile range [IQR]), and the MMSE score post‐FMT was 16.00 (Median, 13.00 – 18.00 [IQR]). The CDR‐SB score pre‐FMT was 10.00 (Median, 5.00 – 12.00 IQR), and post‐FMT was 5.50 (Median, 4.00 – 8.00, IQR). FMT led to changes in the recipient’s gut microbiota composition, with enriched Proteobacteria in pre‐FMT and Bacteroidetes in post‐FMT most pronounced. We found that the genera were reported to be associated with cognitive function. In addition, alanine, aspartate, and glutamate metabolism pathway was found to be significantly different between before and after FMT

Conclusion

This study highlight the important interaction between the gut microbiome and cognitive function. Moreover, this study suggest that FMT may effectively delay cognitive decline in patients with dementia.
Measurement of social connection in people with dementia living in care homes
Authors: Sommerlad Andrew , Liougas Madalena , Livingston Gill , McGilton Katherine S , O'Rourke Hannah M , Bethell Jennifer
Published: June 2023

Background

Social connection is a fundamental human need. For those living in long‐term care (LTC) settings, social connection influences quality of life and care. However, social connection has not been clearly conceptualized, nor is it routinely measured, in LTC. LTC residents have complex health needs, and are separated from previous social networks while residing in communal care environments, so measurement instruments need to be tailored and tested in these settings. Currently, there is no evidence‐based consensus on the best approaches to defining or measuring social connection in LTC homes. In this project, funded by an Alzheimer’s Association/Brain Canada Advancing Research on Care and Outcome Measurement grant, we aim to systematically describe all previous of social connection measures in LTC residents and evaluate their psychometric properties.

Methods

We searched eight databases until November 18th, 2021. We used the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) filter to identify studies reporting instrument measurement properties. We included primary studies reporting ≥1 psychometric property (including validity, reliability, internal consistency, responsiveness) of a measure of social connection (including social engagement/ support/ networks/ isolation, loneliness, and other related constructs), tested among LTC residents. Two reviewers will independently screen titles and abstracts and then conduct full text review.

To assess measure form and content, we will describe the measures and their target settings, and conduct a thematic content analysis on all items. To evaluate psychometric properties, we will assess each measure using the COSMIN risk of bias checklist and summarize the evidence for the nine measurement properties. We will rate the measure overall using a Grading of Recommendations Assessment, Development, and Evaluation approach.

Results

After removing duplicates, our search yielded 5945 studies. We excluded 5818 studies after screening titles and abstracts, leaving 127 papers for full text review.

Conclusions

We will present results of this ongoing systematic review on content and psychometric properties of social connection measures in LTC residents. Through this presentation, we will elicit feedback from stakeholders on our findings to date. This feedback will inform our development of a new measure to assess social connection in people living in LTC homes.
Addressing loneliness among people living with dementia: The key features of personal contact interventions
Authors: O'Rourke Hannah M , Jefferey Nicole , Prestwich Judy , McLean Haydn
Published: June 2023

Background

Interventions to address loneliness among older adults have been developed which target modifiable influencing factors of social contact, social participation, and social support. However, few interventions have been designed specifically to address loneliness for use with people living with dementia. The purpose of this mixed methods study was to identify key features of personal contact interventions for use with people living with dementia.

Method

This was a mixed methods (concurrent triangulation) design using a convenience sample of family, friends, and health care providers of people living with dementia (n = 25). In face‐to‐face sessions, participants were read a short description of two personal contact interventions: an animal contact and a human contact intervention. They completed questionnaires to rate acceptability (adapted Treatment Perception and Preference measure), followed by semi‐structured interviews to explore their perspectives in‐depth. Descriptive statistics and conventional content analysis were completed, and themes from the qualitative analysis were emphasized in the interpretation of results.

Result

A majority (>80%) of participants rated personal contact interventions, with either a human or animal visitor, as being low risk, effective, logical and suitable to address loneliness among people living with dementia. While some form of human contact was viewed as essential for every person living with dementia, appropriateness of animal contact was seen as dependent on the individual characteristics of the person living with dementia. In addition to preventing loneliness, participants highlighted that the benefits of personal contact could include promoting happiness and comfort, offering something to do, and preventing responsive behaviors. For all personal contact interventions with a human or animal, it was important to prepare the contact, focus on meaningful relationships, consider flexible program delivery options, and ensure high quality facilitation of visits.

Conclusion

Personal contact with a human or animal shows promise to address loneliness experienced by people living with dementia when it is facilitated, flexible, and carefully designed to promote meaningful interactions. Future feasibility studies are needed to assess how people living with dementia experience and perceive personal contact interventions.
Cognitive changes predict mortality in people with Alzheimer’s disease: NCGG‐stories
Authors: Nakagawa Takeshi , Sakurai Takashi , Sugimoto Taiki , Ono Rei , Noguchi Taiji , Komatsu Ayane , Uchida Kazuaki , Kuroda Yujiro , Arai Hidenori , Saito Tami
Published: June 2023

Background

Low cognitive function at baseline is a proven risk factor for mortality in people with dementia. However, the prognostic role of long‐term cognitive changes is less studied. This study examined whether cognitive changes predict mortality among people with Alzheimer’s disease (AD).

Method

Data were extracted from a retrospective cohort of Japanese patients attending a memory clinic between 2010 and 2018 (period of visits: M = 4.3 years, SD = 2.1), and a sample of 1,486 AD patients (baseline age 65‐95 years) was analyzed. We conducted a mail survey from 2018 to 2019 to obtain survival information from the patients or their proxies. Cognitive function was assessed by the Mini‐Mental State Examination (MMSE). Baseline age, sex, years of education, and baseline instrumental activities of daily living were included as covariates. Shared‐parameter models were used for longitudinal and time‐to‐event outcomes.

Result

During the follow‐up period, 23.4% of participants died. Shared‐parameter models showed that higher levels and less steep declines in cognitive function reduced the mortality risk (MMSE intercept hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.92–0.99; MMSE slope HR 0.87; 95% CI 0.79–0.96), even after adjusting for covariates.

Conclusion

Our findings suggest that cognitive changes predict mortality independently of baseline cognitive levels in people with AD. Health care professionals should recognize that patients who demonstrate steeper cognitive declines can have a worse prognosis.
Vision impairment in a life course model of potentially modifiable dementia risk factors
Authors: Ehrlich Joshua R , Goldstein Jenna , Swenor Bonnielin K , Whitson Heather , Langa Kenneth M , Veliz Philip
Published: June 2023

Background

There is considerable evidence that vision impairment and blindness are a risk factor for accelerated cognitive decline and incident dementia. Additionally, up to 90% of vision impairment is preventable or has yet to be treated. Nonetheless, vision impairment has not been included in prevailing life‐course models of dementia risk factors used to shape public health policy and research priorities.

Method

We calculated the population attributable fraction (PAF) of dementia for vision impairment and other potentially modifiable dementia risk factors. The relative risk of dementia was derived from published meta‐analyses. Communalities and risk factor prevalence were calculated using cross‐sectional survey data from the 2018 Health and Retirement Study. Data on vision impairment were derived from the CDC’s Vision and Eye Health Surveillance System. All PAF values were weighted for communality (clustering of risk factors).

Result

The 12 risk factors in this model were associated with 59.8% of dementia cases in the U.S (Figure). Hypertension had the highest PAF (12.3%) among all risk factors. Vision impairment had a prevalence of 8.3% and a PAF of 1.8%, which suggests that >100,000 prevalent cases of dementia in the U.S. may have been prevented through healthy vision.

Conclusion

Vision impairment contributes significantly to existing life‐course models of potentially modifiable dementia risk factors and has a magnitude similar to that of some other well accepted risk factors. A majority of vision impairment is modifiable, so this risk factor may represent an important target for future interventional research to prevent dementia.
Macular thickness is associated with whole brain grey matter volume in a mixed cohort of healthy controls and patients with neurodegenerative disease
Authors: Bennett Daniel J , Chou Austin , Oertel Frederike Cosima , Tsuei Torie , Cobigo Yann , Kramer Joel H. , Rankin Katherine P , Ferguson Adam , Miller Bruce L , Green Ari J , Elahi Fanny M
Published: June 2023

Background

Retinal atrophy in CNS neurodegenerative disease (NDD) has been reported by a growing literature base, suggesting that retinal changes may mirror, or even precede, neurodegeneration in the brain. However, understanding of how retinal and brain atrophy are associated in NDD is limited. In a large cohort of healthy aging controls (HC) and patients with confident diagnoses of NDD, we investigated if neuronal tissue loss in the unmyelinated retina is associated with whole brain grey (GM) and white (WM) matter volumes.

Method

We performed optical coherence tomography (OCT) within six months of structural brain imaging (MRI) in 373 patients with NDD (256 frontotemporal lobar degeneration spectrum (FTLD), 87 Alzheimer’s Disease (AD), 16 Lewy Body Disease (LBD), 12 prion disease, 2 with mixed etiology; age [years, mean±SD]:65.6±8.8, gender [male %]:51%, clinical dementia rating (CDR) [median (IQR)]:1 (0.5)) and 117 HC (age:73.8±9.5, gender:48%). 123 subjects (81 FTLD, 20 AD, 5 prion, 17 HC) had at least one follow up exam with both brain and retinal imaging (follow up time[years, median (IQR)]:1 (0.5)). Linear models correcting for age and total intracranial volume (TIV) were used to investigate the relationship between measurements of retinal thickness (µm), and whole brain GM and WM volumes (mm3). Associations between annualized rate of change were modeled for patients with follow up, and were not corrected for TIV.

Result

Cross sectionally, macular thickness was associated with GM (0.62±0.20, p = 0.003) and WM (0.30±0.14, p = 0.030). Inner plexiform layer (IPL; 2.00±0.98, p = 0.038) and outer nuclear layer (ONL; 1.10±0.40, p = 0.005) were associated with GM, but not WM. Annualized rate of IPL (4.1±1.7, p = 0.016) and ONL (1.1±0.5, p = 0.034) change were associated with annualized rate of GM change, but not WM. In FTLD patients alone, rates of macular (2.7±0.6, p<0.001) and GCL (6.1±2, p = 0.005) change were also associated with GM change.

Conclusion

Whole macular thickness and structurally relevant sublayers representing neuron cell bodies (GCL, ONL) and dendritic arbors (IPL, ONL), were associated with GM, but not WM volume changes in a cohort of HC and NDD, with overrepresentation of FTLD. While findings may be limited to FTLD, they support retinal imaging as a biomarker for CNS neurodegeneration.
Agreement between cerebrospinal fluid biomarkers and Amyloid PET in a multicentric cohort
Authors: Guillén Núria
Published: June 2023

Background

Cerebrospinal fluid (CSF) biomarkers have shown incomplete concordance with amyloid‐positron emission tomography (PET). Our goal was to analyze the agreement between CSF biomarkers and amyloid‐PET in a multicenter study.

Method

Retrospective multicenter study (6 centers). Participants who underwent both CSF biomarkers and amyloid‐PET with a maximum time between tests <18 months were included. Biomarkers were considered abnormal according to cut points of each center, describing different ATN profiles: A+T+N+, A‐T‐N‐, others. Amyloid‐PET was classified as positive/negative visually. Agreement between CSF biomarkers and amyloid‐PET was analyzed by overall percent agreement (OPA).

Result

256 participants were included (age 68(SD9), MMSE score 25(SD4)). Diagnoses were mild cognitive impairment or dementia due to Alzheimer’s disease (49%), Lewy body dementia (21%), frontotemporal dementia (10%) and others (20%). Mean time between tests was 4.9 months (SD4,0). 41% were APOEε4 carriers. CSF biomarkers were analyzed with Innotest® (32%) or Lumipulse® (68%). PET tracers employed were 18F‐Florbetapir (71%), 18F‐Flutemetamol (21%) or 18F‐Florbetaben (8%). OPA between single CSF biomarkers and amyloid‐PET was 75% for Aβ1‐42, 75% for pTau181, 74% for tTau. The use of Aβ1‐42/Aβ1‐40 ratio (n = 155) as an indicator of amyloid deposition increased OPA (86%). The use of other biomarker ratios also improved OPA: 88% for pTau181/Aβ1‐42 and 82% for tTau/Aβ1‐42). Agreement of CSF biomarkers with amyloid‐PET was higher in A+T+N+/A‐T‐N‐ cases (94%), mainly when all CSF biomarkers were altered (97%).

Conclusion

The use of CSF biomarker ratios improved their agreement with amyloid‐PET. A+T+N+/A‐T‐N‐ CSF profiles had an agreement with amyloid‐PET higher than 90%.
The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease
Authors: Lu Jiaying , Zhang Zhengwei , Wu Ping , Liang Xiaoniu , Zhang Huiwei , Hong Jimin , Clement Christoph , Yen Tzu‐Chen , Ding Saineng , Wang Min , Xiao Zhenxu , Rominger Axel , Shi Kuangyu , Guan Yihui , Zuo Chuantao , Zhao Qianhua
Published: June 2023

Background

This study aimed to investigate whether an asymmetric tau distribution on PET images could be associated with clinical characteristics and prognosis in prodromal and/or clinical Alzheimer’s disease (AD).

Method

The testing cohort consisted of 60 patients with mild cognitive impairment due to AD and AD dementia from the Alzheimer’s Disease Neuroimaging Initiative – who underwent tau PET imaging with the first‐generation tau tracer [18F]flortaucipir. The validation cohort consisted of an independent sample of 67 patients enrolled from the Shanghai Memory Study who underwent PET tau imaging with the second‐generation tau tracer [18F]APN‐1607. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross‐sectionally compared in terms of demographic and cognitive characteristics, as well as pathological burden. The cognitive trajectories of cognitive decline were analyzed longitudinally.

Result

Fourteen patients (23.3%) in the testing cohort and 26 (38.8%) in the validation cohort showed an asymmetric tau distribution. In both cohorts, cross‐sectional results consistently revealed that an asymmetric tau distribution was associated with an earlier age at disease onset and more severe tau and amyloid burden (Fig 1). In longitudinal analyses, patients with an asymmetric tau distribution were characterized by a steeper cognitive decline (Fig 2).

Conclusion

An asymmetric tau distribution on PET images was consistently associated with an earlier age at onset and more severe pathological features of AD in two independent cohorts. Additionally, this imaging biomarker was longitudinally associated with a more rapid trajectory of cognitive decline.
Ventricular electrocardiographic signatures associated with dementia and plasma Alzheimer’ s biomarkers in older adults: The MIND‐China study
Authors: Mao Ming , Wang Chaoqun , Han Xiaolei , Liu Rui , Dong Yi , Han Qi , Wang Xiaojie , Liu Xinyu , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: June 2023

Background

Cardiovascular risk factors and cardiovascular diseases (CVDs) have been linked with dementia. In addition, amyloid‐β (Aβ) is detected in the heart of patients with Alzheimer’s disease (AD). However, no population‐based studies have yet investigated the interrelationships of ventricular electrocardiographic (ECG) profiles (e.g., QT, JT, QRS intervals, and QRS axis angle) with dementia and plasma Alzheimer’s biomarkers.

Method

This population‐based cross‐sectional study included 5110 participants (age ≥65 years; 57.2% women) from the baseline assessments of the multimodal interventions to delay dementia and disability in rural China (MIND‐China) in March‐September 2018; of these, 1273 had data on plasma Aβ42, Aβ40, total‐tau, and neurofilament light chain (NfL) that were measured using the single molecule array (SIMOA) technology. Ventricular ECG parameters included QT, QTc, JT, JTc, QRS intervals, and QRS axis angle. The DSM‐IV criteria were followed for the diagnosis of dementia, the NIA‐AA criteria for AD, and NINDS‐AIREN criteria for vascular dementia (VaD). Data were analyzed using the general linear models, multinomial logistic models, and restricted cubic splines.

Result

Of the 5110 participants, 296 (5.79%) were diagnosed with dementia (192 with AD; 93 with VaD). The multivariable‐adjusted odds ratios (95% CI) of dementia associated with the quartiles of QT interval were 1.00 (reference), 1.66 (1.11‐2.50), 1.93 (1.25‐3.00), and 1.78 (1.10‐2.91), respectively. QTc, JT, and JTc intervals had analogous associations with dementia, and these ventricular ECG parameters were significantly associated with an increased likelihood of AD and VaD. The restricted cubic spline model suggested a significant association of QRS axis left deviation with VaD. In the plasma biomarker subsample, JT and JTc intervals were associated with multivariable‐adjusted β coefficients (95% CI) of ‐0.15 (‐0.27‐ ‐0.03) and ‐0.11 (‐0.20‐ ‐0.01), respectively, for Aβ42/Aβ40 ratio. The multivariable‐adjusted β coefficients (95% CI) of plasma NfL associated with QT, JT, and JTc intervals were 0.04 (0.01‐0.08), 0.06 (0.02‐0.09), and 0.04 (0.01‐0.07), respectively.

Conclusion

Ventricular ECG signatures for dementia and plasma Alzheimer’s biomarkers in rural‐dwelling older adults are characterized by altered ventricular repolarization and depolarization. These results support the view that Aβ metabolism and neurodegeneration might be involved in the associations of ventricular ECG profiles with dementia.
Alcohol intake affects AD and LATE: A telltale lifestyle from two large‐scale datasets
Authors: Wu Xinxing , Peng Chong , Nelson Peter T , Cheng Qiang
Published: June 2023

Background

AD is not caused by a single factor but by a variety of factors, of which factors are considered to be important. At present, the factors affecting LATE are largely unknown; in particular, the factors that distinguish AD from LATE are yet to be identified.

Method

We leveraged an innovative integrated feature selection‐based algorithm of preprocessing, feature selection, and validation, abbreviated as PFV (Figure 1), to identify important environmental risk factors differentiating subjects with LATE and/or AD from Control with healthy cognition on significantly imbalanced data. PFV was applied on two existing large‐scale datasets, i.e., a discovery dataset (ROSMAP) and a validation dataset (NACC), which comprised subjects with LATE and AD, and Control. Independent validation across datasets was performed in NACC by using chi‐square test and logistic regression analysis.

Result

We retrospectively analyzed the data of 508 subjects in ROSMAP for discovery and 9,256 subjects in NACC for independent validation. In ROSMAP, the sets of risk factors that we identified were usually small. For example, for LATE vs. AD scenario, compared to using all variates, 2 risk factors were identified for the whole cohort with an improvement in AUROC of about 7%, 1 risk factor was identified for Male subpopulation with an improvement of about 26%, 3 risk factors were identified for Female subpopulation with an improvement of about 7%, 2 risk factors were identified for White subpopulation with an improvement of about 6%, and 3 risk factors were identified for >85 subpopulation with an improvement of about 9% (Figure 2 and Table 2). And our results suggest that alcohol intake and living activities are significant risk factors for LATE; for instance, in LATE vs. Control scenario, lifetime daily alcohol intake is the common risk factor for the whole cohort (p‐value: 3.14e‐03), Male subpopulation (p‐value: 4.00e‐02), White subpopulation (p‐value: 1.14e‐03), and >85 subpopulation (p‐value: 4.11e‐03). In NACC, statistical analyses validate the role of alcohol consumption on AD and LATE.

Conclusion

We found that alcohol intake affects AD than LATE, which was first identified on the discovery dataset ROSMAP and then further validated on the across dataset NACC.
Biochemical Characterization of LINC00298, a Non‐Protein Encoding RNA, which when Expressed, Plays a Role in the Development of Early‐Onset Alzheimer’s Disease
Authors: Whitaker Rachel A Hellmann
Published: June 2023

Background

LINC00298 gene was identified through whole‐genome sequencing experiments as an important factor in the development of early‐onset Alzheimer’s disease. The LINC00298 RNA gene product has not been biochemically characterized and it’s physiological role in the development of Alzheimer’s disease remains unknown.

Method

LINC00298 RNA was in vitro transcribed and then bound to Mg2+. The Mg2+ binding event was characterized by gel electrophoresis and UV‐Vis spectroscopy. The LINC00298 RNA was then biotinylated on its 3' end and bound to streptavidin chromatography beads. Affinity chromatography was utilized to determine binding partners for LINC00298 RNA from hippocampal neuronal cell lysate. These binding partners were identified with mass spectroscopy.

Result

LINC00298 RNA undergoes signification structural changes upon binding to Mg2+. Biophysical analysis indicates that these structural changes are secondary and tertiary in nature. Additionally, LINC00298 RNA does have binding partners within neuronal cells, which may shed light on its physiological role in the development of early‐onset Alzheimer’s disease.

Conclusion

LINC00298 RNA is an important gene product in the development of early‐onset Alzheimer’s disease. Though it does not encode for a protein product, this RNA has three‐dimensional structure and has binding partners within neuronal cells.
Nutritional interventions for brain health in patients with Alzheimer’s disease: An expert consensus
Authors: Jiang Jiwei , Xu Jun , Shi Hanping
Published: June 2023

Background

Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is the greatest and sharp increasing challenge for global public health and social care in the 21st century. Being limited options for early diagnosis and the exact pathophysiology of AD, effective therapeutic strategies are still a great challenge. AD is among the least well‐served therapeutic areas for drug treatments. Recently, there has been accumulating evidence that malnutrition and weight loss are frequent and serious presentations of patients with AD, and they also affect the development and progression of this disease, which forms a vicious circle. Accordingly, Mediterranean‐like diet as a protective factor against memory decline and mediotemporal atrophy may be related to a decrease of amyloidosis and tau‐pathology. Moreover, the latest reviews and meta‐analyses have demonstrted that together the modifiable risk factors, including dietary and lifestyle changes, could theoretically prevent or delay 40% of worldwide AD and related dementia. The evidence suggests that nutrition as an important environment factor of AD may participate in the whole stage through multifaceted pathways.It is of further interest how to manage the nutritional status in patients with AD, and whether supplementation of energy and/or specific nutrients could be able to prevent the onset or the development of cognitive decline.

Method

We established a Chinese multidisciplinary working group consistent with officially accepted standards, discussing the nutrition‐related prevention, diagnosis and management in patients with AD based on the international research evidence currently.

Result

We proposed primordial‐primary‐secondary‐tertiary prevention strategies in accordance with the continuous pathological process of AD, and emphasized the important role of nutrition in this new four‐level prevention strategy. Furthermore, we provided the first expert consensus of nutritional interventions for brain health in patients with AD including 26 evidence‐based recommendations, focusing on the nutrition‐related prevention, diagnosis and management.

Conclusion

This consensus emphasizes that nutritional intervention should be early, collaborative, holistic and long‐term. Focusing on the social determinants of health in populations, including diet and nutrition, to maintain optimal brain health and reduce the development of risk factors of dementia have great significance.
A comparative analysis of different cognitive reserve estimates and their relation to connectivity in resting‐state functional MRI
Authors: Ersoezlue Ersin , Buerger Katharina , Dechent Peter , Haynes John‐Dylan , Ewers Michael , Fliessbach Klaus , Kleineidam Luca , Laske Christoph , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Duzel Emrah , Jessen Frank , Rauchmann Boris‐Stephan , Perneczky Robert
Published: June 2023

Background

Cognitive reserve (CR) is a concept that addresses the differences in trajectories of cognitive decline while facing neurodegenerative changes in the brain. Common proxies of CR include demographic or socio‐behavioral measures such as sex and educational/occupational attainment. Recent studies have quantified CR using a residual approach, a direct and cross‐sectional measurement of the discrepancy between estimated cognition and neurodegenerative burden. The associations between these two approaches remain largely unclear.

Methods

Data of 801 participants from the German DELCODE study was used, including 215 healthy controls and 586 individuals with increased risk of AD dementia (61 subjective cognitive decline, 150 mild cognitive impairment and 75 aged 80 years and older with a first‐degree relative with AD). To differentiate similar clusters in tested lifestyle factors, we conducted a dimension reduction method using principal component analysis and consequently derived 8 component factor scores. A residualized memory CR score (CRMEM) was calculated as residuals from a multilinear regression model. Functional connectivity was analyzed using resting‐state fMRI data.

Results

Partial correlation analyses revealed significant positive correlations between CRMEM and component factors 1 (retirement and living), 3 (educational attainment) and 4 (social network and occupational attainment) in the entire cohort and at risk for AD dementia individuals. Higher CRMEM was associated with higher functional connectivity between the hippocampus and regions related to the default‐mode network. Factor scores 3 and 4 were associated with increased rostral hippocampus‐right angular gyrus functional connectivity. A mediation analysis showed a significant indirect effect of factor 3 on the relationship between CRMEM and rostral hippocampus‐right angular gyrus functional connectivity.

Conclusion

CR‐favorable socio‐behavioral factors are correlated with higher CRMEM in healthy aging and AD‐risk groups. Educational attainment might present a rather specific proxy of CR for individuals at AD‐risk. In contrast, mid‐life (occupational attainment) and late‐life factors (retirement years, social network and living status) predict CR both in AD‐risk and healthy aging groups. However, only in the AD‐risk group, hippocampal functional connectivity was higher in individuals with higher CRMEM, mediated in favor of higher educational and female sex, suggesting a close relationship to neural reserve.