bluuebunny/crossref_metadata_2025 huggingface dataset:
Allostatic load measures in elderly subjects with mild cognitive impairment and subjective cognitive decline: a cross‐sectional analysis from the Brazilian Memory and Aging Study
Authors: Barbosa Breno José Alencar Pires , Jesus Maria Clara Ferreira , de Oliveira Maira Okada , Cassimiro Luciana , Avolio Isabella B , Trés Eduardo Sturzeneker , Borges Conrado Regis , Teixeira Thiago Bezerra Moraes , Souza‐Talarico Juliana Nery , Brucki Sonia Maria Dozzi
Published: December 2023

Background

There’s increasing evidence suggesting that chronic stress and persistently high levels of cortisol are related to cognitive dysfunction and neurodegeneration. The Brazilian Memory and Aging Study (BRAMS) is a research initiative for the longitudinal follow‐up of individuals in a tertiary center specialized memory outpatient clinic. The present study aimed to investigate the relationship between markers of chronic stress and cognitive status in BRAMS, making comparisons between participants classified as controls, subjective cognitive decline (SCD) and mild cognitive impairment (MCI)

Method

cross‐sectional study with a subgroup analysis of the BRAMS cohort, in which individuals aged > 60 years had access to a comprehensive neuropsychological classification, clinical, imaging and laboratory measures. The allostatic load index (AL) was measured through anthropometric, endocrinological, cardiovascular, metabolic and inflammatory markers of chronic stress.

Result

77 participants were evaluated, of which 65 met the inclusion criteria. The mean age was 70.2 (+ 6.01) years, with 72% being female and 11 years of schooling (interquartile range 7 – 15). 42 subjects were classified as MCI, 15 as SCD and 8 as controls. There was a significant difference between waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03) and in the measurement of the weighted AL index considering individuals in the extremes values of cortisol (36.9% in the MCI group vs. 27.2% in the SCD group, p = 0.04). In the multivariate analysis, higher education was associated with reduced risk of MCI.

Conclusion

despite a modest sample size, the present work probably represents one of the first research initiatives to address measures of chronic stress beyond cortisol in elderly participants diagnosed with SCD and MCI, with an increased AL in the MCI group. Due to the cross‐sectional nature of the study, the associations found do not allow inferring causality between the measures, which need further validation in the longitudinal follow‐up of the participants.
Socioenvironmental, Stigma, Risk, and Protective Factors Associated With the Health of Latino LGBTQ+ Dementia Caregivers
Authors: Kittle Krystal R.
Published: December 2023

Background

Compared with caregivers of individuals with other chronic conditions, dementia caregivers experience worse emotional and physical health and are twice as likely to say their health has declined due to caregiving. Both Latino and LGBTQ+ populations are underrepresented in dementia caregiving research, though both populations report a higher prevalence of informal caregiving compared with their non‐Latino White and non‐LGBTQ+ counterparts. We aimed to examine associations between socioenvironmental, stigma, risk, and protective factors and global health among Latino LGBTQ+ caregivers of people with dementia.

Method

Data came from a cross‐sectional online survey using a non‐probabilistic sample of English‐proficient, Latino LGBTQ+ dementia caregivers recruited via social media (n = 103). We examined associations using bivariate analyses.

Result

Latino bisexual respondents reported better global health than Latino gay and lesbian respondents. Females had better health than males and transgender respondents reported poorer health than cisgender respondents. Millennials had worse health than Generation X respondents. There were positive associations between global health and months providing care, lifetime discrimination, day‐to‐day discrimination, lifetime victimization, and microaggressions and negative associations between self‐efficacy for surrogate decision making and family quality of life. Respondents providing care to a spouse (versus a parent, another relative, or friend), those living with their care recipient, those who had been asked by a provider whether they needed help caring for themselves or their care recipient, and respondents who had requested information about financial help for their care recipient had better health. Respondents whose care recipients had advanced directives had poorer health than those who did not.

Conclusion

Several socioenvironmental, stigma, risk, and protective factors were associated with the global health of Latino LGBTQ+ dementia caregivers. Latino LGBTQ+ dementia caregivers may be exhibiting signs of resiliency, for example when it comes to discrimination and caregiving demand, and seeking help may be important for their health. Some associations may be confounded by other factors and more research is needed to understand the pathways by which these factors ultimately influence the health of Latino LGBTQ+ dementia caregivers.
Identifying the role of transcriptome in amyloid‐β and tau pathologies in Alzheimer’s disease
Authors: Yu Meichen , Risacher Shannon L , Nho Kwangsik , Saykin Andrew J. ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2023

Background

Amyloid‐β and tau proteins accumulate at distinct neuronal systems in Alzheimer’s disease (AD). However, why specific brain regions are more vulnerable to amyloid‐β and tau pathologies than others remain unclear.

Method

Using two independent cohorts from the ADNI and the IADRC as discovery and replication samples, we studied the relationship between gene expression profiles and amyloid‐β and tau pathologies. In ADNI, we included 583 and 564 participants with amyloid‐β PET and tau PET data, respectively; in IADRC, we included 110 and 78 participants with amyloid‐β PET and tau PET data, respectively. In both cohorts, amyloid‐β pathology was measured by [18F]florbetapir (AV45) and [18F]florbetaben (FBB) PET; tau pathology was measured by [18F]flortaucipir (AV‐1451) PET. The regional vulnerability to amyloid‐β and tau pathologies were estimated by contrasting amyloid‐β and tau PET data between cognitively unimpaired (CU and/or SCD) and patients (MCI and AD). Regional expression profiles for 20,736 protein‐coding genes were derived from brain‐wide microarray‐based transcriptome data from the Allen Human Brain Atlas. We computed spatial associations between gene expression levels and amyloid‐β (gene‐to‐amyloid‐β associations) and tau (gene‐to‐tau associations) pathologies for 60 AD susceptibility genes selected from recent large‐scale GWAS studies.

Result

In both cohorts, AD and MCI showed the expected higher amyloid‐β loads than CU, particularly in the medial parietal cortex, temporal lobe, medial and inferior prefrontal cortices, and superior and middle frontal cortices. In both cohorts, AD and MCI showed higher tau deposits than CU, mainly in the medial temporal lobe, medial and inferior parietal cortices, and inferior and middle temporal cortices. In both cohorts, we identified consistent significant gene‐to‐amyloid‐β and gene‐to‐tau associations after multiple testing adjustment (PFDR < 0.05). Specifically, CNTNAP2 and CLU showed the strongest positive gene‐to‐amyloid‐β associations, whereas TNIP1 and INPP5D showed the strongest negative associations. APOE and BIN1 showed the strongest positive gene‐to‐tau associations, whereas SORL1 showed the strongest negative associations.

Conclusion

We identified replicable regional vulnerability patterns of amyloid‐β and tau pathologies and their relationships to regional gene expression profiles. Better understanding of the regional association of gene expression and amyloid‐β and tau pathologies may foster identification of novel diagnostic and therapeutic targets.
Relationship between occupation and cognitive performance in patients with cognitive impairment. Preliminary study
Authors: Dorman Guido Santiago , Boccazzi Julian Fernandez , Flores Ignacio , O'Neill Santiago
Published: December 2023

Background

Previous studies showed the protective effect of cognitive reserve for the development of cognitive impairment and dementia symptoms. Some factors have been postulated that may influence cognitive reserve, including education, participation in cognitively stimulating activities, and occupation. It has been observed that certain occupations have better cognitive performance and different professions may generate better functioning in certain cognitive domains than others. The aim of this study is to assess whether there is greater strength in certain cognitive domains related to the occupations of patients with subjective memory complaints or mild cognitive impairment diagnosis.

Method

Retrospective observational study with patients under follow‐up in a memory clinic in Buenos Aires, Argentina. Patients with >17 education years, > 50 years with a diagnosis of subjective memory complaint and/or mild cognitive impairment of any origin were included. Subjects with dementia were excluded. The occupations were classified according to the ISCO‐88 (2008 International Labor Organization) utilizing professionals’ subcategory. A complete cognitive evaluation was performed in all the patients, including memory, attention, language, executive functions, and visuospatial domains. For the statistical analysis, the z scores of the results of the different cognitive tests were used and parametric student`s‐t tests were performed using the Graphpad software,

Result

A total of 57 patients from our center were included to date. The mean age was 71 (55‐85), years of education 19 (17‐25) and a total of 35 (61%) women. The mean of Addenbrooke’s Cognitive Examination (ACE) was 91.3 (82‐99). The predominant occupation was in the health category with a total of 24 (42%) patients. No statistically significant differences were obtained in the values of the different cognitive tests of each occupational category and the value of the total population.

Conclusion

The study has not shown significant differences between specific cognitive variables and occupation in patients with cognitive impairment. However, a larger number of subjects would be needed to support this statement. It is important to note that extra‐work activities of patients that can also influence their cognitive performance have not been taken into account.
Triage through motoric cognitive risk syndrome: Is it possible to assess the risk of developing dementia in fast‐paced acute care settings?
Authors: Gonzaga Marilia Cristina de Oliveira , Takahashi Silvia de Fatima , Ferraz Ana Carolina , Suemoto Claudia Kimie , Aliberti Marlon Juliano Romero
Published: December 2023

Background

Motoric cognitive risk syndrome (MCR) is a practical tool for identifying independent community‐dwelling older people at risk of developing dementia.1 Whether this tool could be efficient in fast‐paced acute care settings, where clinicians have limited resources, remains to be discovered.2 We investigated the performance of MCR to identify acutely ill older outpatients at risk of developing dementia. We also estimated associations of MCR with incident disability, an age‐related condition highly associated with cognitive impairment.

Method

Cohort comprising older people in need of intensive management (intravenous therapy, laboratory test, radiology) to avoid hospitalization in Brazil. We excluded those with dementia diagnosis or experiencing disability. MCR was defined as presence of memory complaints and slow gait (one standard deviation below age‐ and sex‐specific gait speed means). Over a 3‐year follow‐up, investigators blinded to baseline data assessed the outcomes: (1) dementia diagnosis through detailed reviews of medical records and (2) incident disability (need for help) to execute basic activities of daily living (ADL) and take medications through structured telephone interviews. To investigate associations of MCR with outcomes, we used Fine‐Gray models (considering death as competing risk) adjusted for routine measures (sociodemographic factors, comorbidities, depressive symptoms, and weight loss). We also computed differences between Harrell’s C‐indexes to estimate whether MCR improves outcome discrimination when added to the routine measures.

Result

Among 610 patients (mean age = 77±8 years, women = 63%, non‐white = 40%), the MCR prevalence was 8% (Table 1). Patients with MCR presented a 3‐fold increased risk of developing dementia compared to those without the syndrome (27% vs. 8%; adjusted sub‐HR = 3.2; 95%CI = 1.6‐6.7) (Table 2). MCR was also associated with higher risks of incident disability in ADL and taking medications–an activity highly related to cognitive functioning. When added to routine measures, MCR remarkably improved the discrimination of models predicting dementia (Harrell’s C‐index = 0.76 vs. 0.69, p = 0.03) (Table 3).

Conclusion

MCR showed excellent performance in predicting the risks of developing dementia and disability among acutely ill older outpatients. The increase in dementia prevalence worldwide demands tools like MCR to expand the identification of high‐risk older people, even in fast‐paced acute healthcare settings where clinicians have limited time and resources.
Sex differences for clinical correlates of substantia nigra neuron loss and Lewy body pathology
Authors: Bayram Ece , Coughlin David G
Published: December 2023

Background

Lewy body pathology staging and substantia nigra neuron loss levels are associated with clinical features in Lewy body dementia (LBD). Compared to women, neocortical Lewy body pathology is more common and co‐pathologies are less common in men. Clinical features of people with limbic and neocortical Lewy body also differ based on sex, although sex differences for additional Lewy body pathology stages or nigral neuron loss are unclear.

Method

Data was obtained from the National Alzheimer’s Coordinating Center Uniform Data Set (UDS) and Neuropathology Data Set for UDS visits conducted between September 2005 and August 2019. Analysis included 31 women and 62 men from 25 AD Research Centers with Lewy body pathology and substantia nigra neuron loss data, excluding those with other neuropathologic diagnoses including moderate/severe Alzheimer’s disease. Linear models assessed the sex differences for clinical associations of nigral neuron loss level and Lewy body pathology staging controlling for age at last visit.

Result

Women were older at last visit and at death, had less years of education than men (Table 1). Men were more likely to have a clinical LBD diagnosis, had cognitive decline at a younger age, worse dementia at last visit, and higher levels of Lewy body pathology staging and nigral neuron loss. Higher Lewy body pathology stage was associated with more nigral neuron loss more for men compared to women (Table 2). Higher Lewy body pathology stage and greater degrees of nigral neuron loss were associated with more severe dementia and behavioral symptoms and a higher likelihood for a clinical Lewy body diagnosis in men compared to women.

Conclusion

Lewy body pathology staging and the level of substantia nigra neuron loss may be worse for men compared to women. These data also suggest that Lewy body pathology and nigral neuron loss affect men more severely than women in terms of dementia severity and behavioral profiles associated with LBD. The blunted clinical manifestations of these pathological features in women add to the difficulty in accurate diagnosis and future work on the reasons for women’s resilience to these pathological features is needed.
Using the RE‐AIM framework to help implement an educational intervention for improving the care of persons with behavioral and psychological symptoms of dementia in primary care
Authors: Stone Jonathan A , Schroeder Molly , Albrecht Tammi , LeCaire Tamara J. , Carlsson Cynthia M , Walaszek Art
Published: December 2023

Approximately 90% of persons living with dementia (PLWD) experience behavioral and psychological symptoms of dementia (BPSD) over the course of their illness, including aggression, psychosis, and depression. With a growing lack of access to specialty geriatric care, most people with BPSD will receive care from their primary care providers. Many primary care practices lack knowledge, self‐efficacy, and established pathways to expert advice for managing these complex behaviors. We have developed a comprehensive educational intervention for primary care providers and clinical staff to help them better address BPSD. The educational intervention combines two complementary approaches: the academic detailing model and the DICE ApproachTM (DICE). In a recent pilot with two primary‐care integrated memory clinic teams, we noted improvements in provider knowledge and clinical staff self‐efficacy and comfort in BPSD and dementia care after 6‐months of participation in academic detailing and DICE training. In our current study, we use the RE‐AIM framework to guide the implementation planning for our educational intervention for primary care providers and clinical staff to help them better address BPSD. The RE‐AIM framework is a widely used tool for evaluating the implementation of health interventions to ensure they are both effective and sustainable. Twenty semi‐structured interviews will be completed among providers practicing in one of two primary care integrated memory clinics who participated in the pilot program (champions) and among their generalist primary care colleagues with no to minimal program experiences (novices), in one urban and one rural healthcare system. The RE‐AIM framework informed the design of our semi‐structured interviews and will help to frame content analysis for identifying potential barriers to implementation, for scale‐up to generalist primary care teams. Five interviews have been completed to date. Qualitative analyses are also underway, and results will be presented. Findings from this study will be used to develop an implementation plan for a future randomized controlled trial to measure the effectiveness of this intervention on health outcomes in PLWD and BPSD.
Discovery‐based proteomics identifies plasma proteins that predict longitudinal cognitive decline in older adults over a 7‐year follow‐up period
Authors: Kresge Hailey A. , Patterson Khiry L , Libby Julia B. , Robb W Hudson , Arul Albert B , Choi Min Ji , Oliver Nekesa , Whitaker Marsalas D , Moore Elizabeth E. , Houston Michelle L , Pechman Kimberly R. , Dumitrescu Logan C , Gifford Katherine A. , Hohman Timothy J. , Robinson Renã AS , Jefferson Angela L.
Published: December 2023

Background

Recent technological advances have enabled large‐scale proteomic profiling of plasma and especially in studies of Alzheimer’s disease. However, studies that have comprehensively examined longitudinal cognitive decline as an outcome from plasma protein levels prior to the onset of clinical dementia are limited. This project aimed to identify plasma proteins predictive of cognitive decline across a robust neuropsychological protocol over a 7‐year follow‐up period.

Methods

Vanderbilt Memory and Aging Project participants (n = 333, 73±7 years, 41% female) free of clinical dementia at study entry underwent fasting blood draw and comprehensive serial neuropsychological assessment over a 7‐year period (mean follow‐up = 5.8 years). Plasma samples were subjected to multiplex liquid chromatography tandem mass spectrometry analysis to quantify cross‐sectional protein abundances for each participant at study entry. Normalization of proteomic data adjusted for batch effects, high levels of missingness, and log2 transformation. Linear mixed‐effects regressions related protein levels to longitudinal neuropsychological outcomes, adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E ε4 status, and follow‐up time. False discovery rate correction was applied to the a priori significance threshold.

Results

Initial proteomics analyses yielded 3,784 proteins, of which 686 were used as analytical predictors following quality control, post‐acquisition filtering, and data normalization. Regression analyses resulted in 86 proteins which predicted longitudinal decline in global cognition, as assessed by the Montreal Cognitive Assessment. In analyses with individual neuropsychological domains as outcomes, 144 proteins predicted longitudinal decline in at least one neuropsychological domain [episodic memory (40 proteins), language (72 proteins), information processing speed (99 proteins), executive function (22 proteins), visuospatial skills (55 proteins)]. There was a smaller number of proteins (i.e., five) that were predictive of longitudinal cognitive decline across all domains.

Conclusion

We conducted large‐scale proteomics analyses and identified 144 plasma proteins at study entry among a cohort of older adults free of clinical dementia that predict subsequent decline in cognition over a 7‐year follow‐up period. Five of these proteins were predictive of decline across all domains suggesting these proteins may represent biological pathways that adversely affect brain health with increasing age. Replication is needed to validate identified proteins as potential biomarkers of cognitive decline.
Amyloidosis at Putamen Predicts Vulnerability to Alzheimer’s Disease
Authors: Yang Zhengshi , Cummings Jeffrey L. , Cordes Dietmar ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

Background

Using merely cortical amyloid burden in a binary approach was commonly adopted for determining if an individual is under AD pathology in both clinical trials and basic research. Subcortical amyloid, compared to cortical amyloid, showed a larger inter‐subject heterogeneity, which may provide valuable insights to their vulnerability to Alzheimer’s disease beyond cortical amyloid.

Method

A total of 1344 individuals from ADNI database had 18F‐AV45 amyloid PET scans available. Regional AV45 signal was computed by averaging the signal from gray matter voxels in each region and then normalized to the mean signal in the composite reference region [1, 2]. The cortical AV45 was averaged over extensive regions consisting of frontal, anterior/posterior cingulate, lateral parietal, and lateral temporal regions. The AV45 signal in the subcortex, including putamen and caudate, were also computed. Only the participants under AD pathology, determined based on cortical amyloid positivity, were included in the analysis. The association analysis between subcortical AV45 and cognition was conducted before and after adjusting cortical AV45. A linear fitting of cortical AV45 and AV45 at putamen was conducted and participants were categorized into high (HighP), middle (MidP) and low (LowP) putamen amyloid group thresholded with ±0.5 standardized residuals. Statistical analysis was carried out to evaluate the difference of clinical diagnosis, hippocampal volume and APOE ε4 genotype. The relevance of amyloid at putamen with the rate of cognitive decline was examined.

Result

Putamen, compared to caudate, had a stronger association with ADAS‐cog13 and MoCA, such an association remained exist after adjusting cortical AV45. Despite distinct AV45 at putamen, participants in LowP, MidP and HighP groups had no cortical AV45 difference. The AV45 at putamen was significantly higher in individuals with more ε4 alleles (ε4 homozygous > ε4 heterozygous > non‐ ε4) and more advance clinical stages (Dementia > MCI > CN). The individuals with higher AV45 at putamen had smaller hippocampal volume and faster cognitive decline.

Conclusion

Our finding suggested that amyloidosis at putamen is a valuable imaging marker beyond cortical amyloid in predicting if a participant is more vulnerable to Alzheimer’s dementia.
Lexical features for repetition task: Turkish language perspective
Authors: Öz Didem , Gorno‐Tempini Marilu , Tee Boon Lead
Published: December 2023

Background

Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome that presents with speech and language impairments and is commonly classified into three variants based on varying symptomatology and pathology: semantic (svPPA), nonfluent/ agrammatic (nfvPPA), and logopenic variants (lvPPA). While more than 85% of the world population don’t speak English language as their first or second language, PPA research has largely focused on English speakers. Thus, we may lack adequate understanding to PPA symptoms of typologically different languages. Turkish language is an agglutinative language that commonly combines multiple morphemes in a word. Therefore, Turkish words are frequently high in syllables, morphemes, and words. Repetition test is a frequently used tool to diagnose lvPPA patients by assessing auditory verbal short‐term memory function. However, the capacity for auditory verbal short‐term memory has been known to be influenced by time and morphological structure, which are generally more complex in Turkish. Our study investigates the lexical features critical for repetition task for Turkish language speakers.

Method

In this study, Turkish‐speaking participants are tasked to repeat six lists of words. List 1 and 2 consist of real and pseudo‐words with one morpheme and one word but increasing in syllables; List 3 and 4 comprised of real and pseudo‐words with increasing number of morphemes and syllables; and List 5 and 6 contained words with increasing morphemes, syllables and words. We then studied the performance of cognitively normal and PPA participants when repeating these lists of words and investigated the effect of number of morphemes, syllables and words.

Results

A total of 15 Turkish‐speaking controls and 12 PPA individuals (7 lvPPA, 1 nfvPPA, 4 svPPA) completed the repetition task. Individuals with svPPA and lvPPA scored significantly lower than controls when repeating List 5 and 6 (p = 0.05 and p = 0.03 respectively). Using general linear model, when covarying for number of words, morphemes, and syllable, we found that repetition performance in Turkish‐speaking participants is predicted by the number of words, morphemes, and syllables in both real and pseudo‐word lists.

Conclusion

When designing repetition task for speakers of agglutinative or polysynthetic languages, lexical features such as number of morphemes and syllables might need to be accounted.
Exploratory research on Neurogranin ratios for biomarkers of neurodegeneration
Authors: Kaneko Naoki , Takahashi Ryota , Kato Takashi , Arahata Yutaka , Sekiya Sadanori , Iwamoto Shinichi , Tanaka Koichi , Nakamura Akinori ,   BATON study group
Published: December 2023

Background

Neurogranin (Ng) is a cerebrospinal fluid biomarker for synaptic dysfunction at early stage of Alzheimer’s disease (AD). It has been reported that some truncated forms from Ng is increased in AD brain tissue. However, the clinical significance of Ng forms in plasma has remained unclear. We have developed a simultaneous detection method of a plurality of Ng forms in plasma by using immunoprecipitation combined with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (IP‐MALDI‐MS). In this study, we applied the IP‐MALDI‐MS technique to investigate blood‐based biomarkers for neurodegeneration.

Method

Plasma samples were obtained from cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer’s dementia (AD) and non‐Alzheimer’s dementia (non‐AD) individuals in National Center for Geriatrics and Gerontology. These subjects were classified as Aβ positive and negative based on PET with PIB tracer. Ng forms were immunoprecipitated from the samples spiked by stable isotope‐labeled (SIL) Ng peptides using magnetic beads coupled with anti‐Ng monoclonal antibody. After the IP was performed two times consecutively, Ng forms eluted from antibody beads were applied on the MALDI plate. SIL‐Ng peptides were used as internal standards for normalizing an intensity of each endogenous Ng form in plasma.

Result

We calculated intensity ratio of a Ng form‐to‐other Ng form (Ng ratio) in all combinations of peaks corresponding to mass of Ng forms. To investigate the possibility of Ng as a biomarker for neurodegeneration, we screened the Ng ratios with the difference between CN and Aβ positive AD or Aβ negative non‐AD. Eleven Ng ratios were significantly higher in the Aβ positive AD and Aβ negative non‐AD groups than the CN group. In ROC analyses, AUC values greater than 0.750 were found in discriminating the Aβ positive AD or Aβ negative non‐AD group from the CN group. Among the eleven Ng ratios, five were significantly correlated with MMSE (ρ←0.400).

Conclusion

Some Ng forms cleaved at or nearly the IQ domain have been found in the AD brain, which suggests the function loss of Ng in synaptic plasticity. Increasing Ng ratios in plasma may be biomarker candidates for synaptic dysfunction involved in the change of Ng forms in the brain.
Longitudinal cortical thinning is associated with cognitive decline in MCI and Alzheimer’s disease in the Korean population
Authors: Yu Meichen , Risacher Shannon L , Yi Dahyun , Byun Min Soo , Lee Jun‐Young , Craft Hannah , Sohn Chul‐Ho , Nho Kwangsik , Lee Dong Young , Saykin Andrew J.
Published: December 2023

Und

Alzheimer’s disease (AD) is characterized by cognitive dysfunction likely secondary to progressive neurodegeneration in the brain. However, to what extent regional cortical thickness (CT) changes are related to cognitive decline in the Asian population remains unclear.

Method

We measured CT using Freesurfer v6 from T1‐weighted magnetic resonance imaging (MRI) data in 603 Korean participants, including 71 young and 288 old cognitively unimpaired (CU young and CU old), 149 with mild cognitive impairment (MCI), and 92 AD from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). Cognitive function of each participant was quantified by the MMSE. MRI and cognitive data were acquired at baseline (n = 603) and a 2‐year follow‐up visit (n = 380). Linear mixed‐effect models were used to estimate diagnosis group, time, and group‐by‐time interaction effects on CT measurements, with age, sex, and education as covariates. Pearson’s correlations between CT measurements and MMSE total score were computed, corrected for multiple comparisons by false discovery rate (FDR).

Result

At baseline, CU old participants had lower CT values than CU young participants in the inferior parietal cortex and frontal and parietal regions. In comparison with CU old participants, MCI and AD showed widespread lower CT values, more pronounced in the medial temporal lobe (i.e., the entorhinal cortex and parahippocampal gyrus), inferior temporal cortex, medial prefrontal cortex, and medial parietal cortex (i.e., the posterior cingulate cortex and precuneus), with AD lower than MCI in these regions. These regions also showed the most longitudinal atrophy in both AD and MCI over 2 years. AD patients showed faster and more widespread atrophy patterns than MCI and CU old participants. We identified significant (PFDR<0.05) positive linear correlations between cognitive decline and regional CT measurements, particularly in regions showing significant cortical thinning across time.

Conclusion

In this study, we replicated the typical cross‐sectional and longitudinal brain atrophy patterns, and relationships with cognitive decline in an Asian cohort. Our findings support the generalizability of atrophy patterns in MCI and AD, suggesting common neurobiological mechanisms underlying AD symptoms across different ethnoracial populations.
Older adults dancing their way to health: a systematic review of the effects of dance interventions on cognition, anxiety, and depression
Authors: Jaldin Michelle A , Balbim Guilherme Moraes , Pinto Juan M , Negrete Miguel , Castillo Crystal , Khanna Sonam , Brunskill Amelia A , Marquez David X.
Published: December 2023

Background

Dance is a form of physical activity that is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive, and social elements (Merom et al, 2013). Many studies have showed the benefits of physical activity on older adults; however, no studies have showed the impact of formal and traditional dance (salsa, bachata, and ballroom dancing) on older adults which makes this review unique. This systematic review (SR) will synthesize dance interventions that include formal and traditional dance and their influence on cognition, anxiety and/or depression.

Method

Our focus is on dance alone; or dance combined with other behavioral strategies (e.g., cognitive, or social program). Three reviewers screened titles, abstracts, full texts and completed data extraction. If disagreements occurred from screening, all reviewers would meet and vote on whether to include or exclude article. If disagreements occurred in data extraction, two extractors would discuss and agree upon a conclusion. If agreement was not met, a senior author would vote. Articles included were 1) published/peer‐reviewed 2) randomized controlled trials (RCT) of a dance intervention that contain at least one of our three outcomes 3) included only dance as a physical component and no other physical components. Participants were individuals cognitively unimpaired or with mild cognitive impairment aged 60 and over.

Result

Sixteen studies were included in the SR for qualitative review. Twelve articles examined cognition, one article examined depression, one article examined cognition, anxiety, and depression and two articles included cognition and depression. Our SR showed that dance interventions can potentially influence cognition. There were no changes in anxiety and although two of three articles examining depression showed significant effects, there is not enough evidence in literature to suggest that dance interventions can potentially influence anxiety and/or depression as there is a small number of articles that studied anxiety and/or depression.

Conclusion

While literature suggests dance interventions potentially influence cognition, depression, more dance interventions are needed on depression, anxiety, and overall mental health. It would also be interesting to examine/compare if different dances affect certain cognitive domains or mental health outcomes more than others.
Baseline diet quality of participants in AU‐ARROW trial based on adherence to the MIND diet recommendations
Authors: Chen Juliana , Castro Carolina B , Fernando Malika , Fuller Stephanie Jane , Jahan Farzana , Brown Belinda M , Loo Ruey , Sohrabi Hamid R , Martins Ralph N , Gardener Samantha L
Published: December 2023

Background

The Mediterranean‐Dietary Approaches to Stop Hypertension (MIND) diet is rich in leafy green vegetables, legumes, berries, wholegrains, fish, nuts, and olive oil and low in red and processed meats and discretionary foods (high in saturated fat, added sugar and added salt). Following a MIND diet is associated with a reduction in risk of cognitive decline and dementia. The lifestyle intervention known as the AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU‐ARROW) is undergoing recruitment of participants. Here we report on the dietary quality of participants to date, based on their adherence to the MIND diet.

Method

A self‐administered MIND diet questionnaire was completed by participants in the online REDCap platform as part of the screening surveys to determine participant eligibility into the AU‐ARROW trial. Eligible participants were required to have a ‘poor diet’, which was a MIND diet score of ≤9 out of a maximum MIND diet score of 14. Comparative statistical analyses were conducted to determine the differences in dietary quality between eligible and ineligible participants.

Result

From the 39 participants who were screened to date, 16 participants were ineligible, and 23 were eligible. Ineligible participants had a higher total MIND diet score (mean = 10.5(SD = 0.6)) compared with eligible participants (mean = 7.5(SD = 1.8)). For ineligible participants, there was greater proportion adhering to MIND diet recommendations for fish, nuts, and poultry. No eligible participants adhered to MIND diet recommendations for leafy green vegetables, berries, and wholegrains. There was general compliance to recommendations for red meat and butter intake among both groups, but a smaller proportion of eligible participants adhered to the MIND diet recommendations for fried foods, sweets, and cheese, compared to ineligible participants.

Conclusion

Overall, improvements to the diet quality of both eligible and ineligible participants are required. Particularly for participants eligible to the AU‐ARROW trial, a focus on improving adherence to core food group recommendations are required not only for cognitive health but also for general health and prevention of other chronic diseases. Education and counselling from dietitians are critical for supporting participants in dietary behaviour change.
Deep learning‐based SWAT‐TAB approach for Identifying Genetic Variants using Whole Genome Sequencing
Authors: Jo Taeho , Nho Kwangsik , Saykin Andrew J.
Published: December 2023

Background

Deep learning has been employed in various genetic studies, but use with large‐scale datasets, such as whole genome sequence (WGS) data, can be challenging due to the high‐dimension low‐sample‐size (HDLSS) problem. In such studies, the number of features (genetic variants) may be orders of magnitude larger than the number of samples, which can impact the applicability of deep learning.

Methods

In this study, we aimed to identify genetic variants associated with Alzheimer’s disease (AD) using a modified version of the SWAT‐CNN1 approach called SWAT‐TAB that addresses the HDLSS problem. The main modification to the original SWAT‐CNN approach was the incorporation of the Tabnet2 algorithm in the second step (Fig. 1A). This algorithm determines associations between features and selects the most relevant ones for a given label using a concept called sequential attention. This calculates the importance of a feature at each step and create a trainable mask based on this information. We applied this modified approach to ADSP WGS data for Chromosome 19, using 7,416 samples (4,266 AD and 3,150 cognitively normal) and 204,486 SNP features.

Results

rs429358, rs7256200, rs1969899716, and rs10414043 were the most important features on Chromosome 19 reflecting known AD genes such as APOE and APOC1, as well as several novel genetic features (Fig. 1B). The SWAT‐TAB approach demonstrated improved execution speed, with a reduction in processing time per SNP by 11.58%. The SWAT‐TAB also demonstrated improved reproducibility and ease of implementation as it only required one layer for execution, compared to the original approach which required as many layers as the number of features in the window.

Conclusion

Our deep learning‐based SWAT‐TAB approach showed significant improvement in execution speed, reproducibility, and ease of implementation compared to the original approach. This method appears very promising for identifying genetic variants associated with AD and constructing accurate classification models. Ongoing studies will determine the potential utility of this approach in larger analyses of WGS data beyond the initial results obtained for Chromosome 19.
Pathways to selective vulnerability in neuromodulatory subcortical structures during the early pathogenic stages of Alzheimer’s disease
Authors: Ehrenberg Alexander J. , Pereira Felipe Luiz , Suemoto Claudia Kimie , Leite Renata Elaine Paraizo , Rodriguez Roberta Diehl , Paes Vitor Ribeiro , Ferretti‐Rebustini Renata Eloah de Lucena , Ferrioli Eduardo , Nitrini Ricardo , Jacob‐Filho Wilson , Pasqualucci Carlos Augusto , Grinberg Lea T.
Published: December 2023

Background

The two main catecholaminergic members of the isodendritic core nuclei are the substantia nigra (SN) and the locus coeruleus (LC). Despite cytoarchitectural and neurochemical similarities between the two nuclei, the LC is significantly more vulnerable to early degenerative changes in tauopathies like Alzheimer’s disease (AD) as compared to the SN. Here, we seek to use the gradient of vulnerability in these catecholaminergic nuclei to identify pathways associated with vulnerability in early AD pathological stages.

Method

This cohort includes individuals with no neuropathologic entities and Alzheimer’s disease proteinopathic stages. Individuals with TDP‐43, Lewy Body, or Chronic Traumatic Encephalopathy pathologic entities were excluded. The LC and SN was dissected from frozen human brainstem tissue using macroscopic anatomic features. To compare the LC and SN, only cases below Braak III with sufficient RNA from both nuclei were included. The Nanostring nCounter platform was used to probe specific pathways related to neurodegenerative processes. DBH and SLC6A3 served as confirmatory readouts of accurate anatomic sampling of the LC and SN. Differential gene expression analysis was used to evaluate patterns of gene expression that differentiate the two nuclei. Annotated gene sets were evaluated using global significance scores (GSS), a representation of cumulative t‐statistics for relevant genes.

Result

The LC and SN were collected from 26 cases (Figure 1) eligible for this analysis. Accurate dissections were confirmed by differential expression of DBH (p = 1.38e‐9) and SLC6A3 (p = 4.5e‐16). Among the differentially expressed genes (Figure 2), genes associated with microglia activation (GSS = 2.35), oxidative stress (GSS = 2.17), and lipid metabolism (GSS = 2.00) significantly differentiated the LC and SN.

Conclusion

The LC and SN serve as examples of differentially vulnerable nuclei at the earliest neuropathologic stages of AD. Cell intrinsic factors, physiological demands, vascular contributions, and exposure to extrinsic factors like toxins are thought to contribute to the LC’s early vulnerability. Here, we show that neuroinflammation and oxidative stress pathways are likely central to differential vulnerability at the earliest stages of Alzheimer’s disease and may represent targets for intervention in prodromal stages.
The role of biofluid markers in predicting near‐term cognitive impairment
Authors: Yakoub Yara , Ashton Nicholas J. , Karikari Thomas K , Montoliu‐Gaya Laia , Schöll Michael , Spreng R. Nathan , Rosa‐Neto Pedro , Soucy Jean‐Paul , Breitner John C.S. , Zetterberg Henrik , Blennow Kaj , Poirier Judes , Villeneuve Sylvia ,   PREVENT‐AD Research Group
Published: December 2023

Background

Alzheimer’s disease (AD) has been defined as a biological construct that can be determined using in vivo biomarkers. Recent studies confirmed the clinical value of the AT(N) framework when using Aβ and tau positron emission tomography (PET) scans in predicting progression from cognitively unimpaired to MCI. Our study aims to investigate if plasma biomarkers can yield similar predictive performance to PET biomarkers, and to also compare against cerebrospinal fluid (CSF) biomarkers

Method

Individuals from the PREVENT‐AD cohort were included in the study. Participants had Aβ and tau plasma measurements and at least one year of clinical follow‐up thereafter (n = 278). A subset of participants had CSF measurements (n = 102) and/or PET scans (n = 133) also with 1‐year clinical follow‐up. Participants were cognitively unimpaired at the time of all biomarker measurements. MCI diagnoses were made by clinical consensus among expert clinical and research staff blind to plasma, CSF, PET, MRI and APOE genotype. We established thresholds of plasma and CSF Aβ and tau positivity based on >80% specificity in identifying individuals with significant levels of Aβ‐PET (plasma Aβ42/40 = 0.057; plasma pTau181 = 7.53 pg/mL; CSF Aβ42 = 961.37; CSF pTau181 = 66.59 pg/mL). Aβ ([18F]NAV4694) and tau ([18F]AV1451)PET thresholds were defined by the mean plus 2 standard deviations from young participants (Aβ SUVR cut‐off = 1.17; tau SUVR cut‐off = 1.24).

Result

36.8% (7/19) of the A+T+ plasma group progressed to MCI, 50% (4/8) of the A+T+ CSF group progressed to MCI, and 46.6% (7/15) A+T+ PET group progressed to MCI (Fig. 1).We found differences in MCI progression status between the A+T+ group compared to the A‐T‐ and A+T‐ groups across all biomarkers’ measurements, with the A+T+ group always showing a higher rate of progression than the other two groups (post‐hoc chi‐square analyses; p<0.05).

Conclusion

Abnormal levels of Aβ and tau plasma biomarkers can help predict near‐ term progression to MCI. When plasma thresholds are derived based on PET data, however, plasma biomarkers have a slightly lower specificity than PET and CSF biomarkers, and both plasma and CSF biomarkers are less sensitive than PET biomarkers.
NetPRISBI‐AD: Network‐based Polygenic Risk Scoring model with Brain Imaging for Alzheimer’s Disease
Authors: Lee Dong‐gi , Jung Sang‐Hyuk , Park Sunghong , Shen Li , Shin Hyunjung , Kim Dokyoon ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

Background

The amount of gray matter can measure the structural characteristics of the brain, and the deterioration of brain function can be evaluated accordingly. In particular, the lower the amount of gray matter in areas involved in memory, the lower the cognitive function, eventually affecting the onset of dementia, such as Alzheimer’s disease (AD). Although there are various factors for changes in gray matter volume, genetic factors are also closely related. In addition, genetic factors are not only independently involved in biological activities, but also have complex interactions.

Method

In this study, we construct a SNP network that reflects interactions between SNPs and propose a model that can predict the risk score for AD and the gray matter volume of the brain by region from the SNP network. First, in the SNP network, interactions between SNPs are measured as similarities based on the linkage disequilibrium score. Then, the proposed method constructs a regression model to predict brain volume and risk scores for AD using feature propagation, which is conducted to refine existing genetic variant information.

Result

The proposed method was applied to data including both genetic and brain imaging information among UK Biobank (UKBB; 8,273 cases and 25,353 controls, total 33,626 participants) and Alzheimer’s Disease Neuroimaging Initiative (ADNI; 202 cases and 720 controls, total 922 participants) data. The results were cross‐validated from the two datasets and compared with other models including the conventional polygenic risk score with pruning and thresholding (PRS‐PT) model. Compared to the other methods, the proposed method showed outstanding performance and the discovery of genetic variants and brain regions affecting Alzheimer’s disease.

Conclusion

We proposed the framework for predicting the volume of the brain with refined features of SNP that reflects the interactions between elements. The results revealed that genetic relations and inferring brain volumes are crucial for enhancing AD risk prediction. Furthermore, through the proposed method, it is expected that understanding and interpreting the phased mechanism of the onset of AD through brain lesions from genetic variants will be possible.