bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the Default Mode Network and Striatal Circuits in the Expression of Depressive Symptoms in Premanifest Huntington’s Disease
Authors: Barta Tamrin , Novelli Leonardo , Georgiou‐Karistianis Nellie , Stout Julie , Loi Samantha M , Glikmann‐Johnston Yifat , Razi Adeel
Published: December 2023

Background

Huntington’s Disease (HD) is increasingly being conceptualised as a circuitopathy (Hannan 2018) and two large‐scale brain networks surmised to contribute to the expression of depressive symptoms in premanifest HD (pre‐HD) include frontostriatal circuitry and the default mode network (DMN). The effective connectivity of these networks in pre‐HD in association with depression was investigated using Dynamic Causal Modelling.

Method

We analysed 3T resting state fMRI data from 93 pre‐HD participants (51.6% females; mean age = 42.7). Neuropsychological assessment included history of depression, the Beck Depression Inventory, 2nd Edition (BDI‐II) and the Hospital Anxiety and Depression Scale, depression subscale (HADS‐D). An optimal cut‐off score recommended for use in HD populations categorised clinically significant depressive symptoms (De Souza, Jones, and Rickards 2010). Brain regions of interest included the medial prefrontal cortex, posterior cingulate cortex, bilateral hippocampus, bilateral caudate, and bilateral putamen. Spectral Dynamic Causal Modelling (Friston et al. 2014; Razi et al. 2015) was used to estimate subject level connectivity and Parametric Empirical Bayes (Friston et al. 2016) was employed to estimate group level effective connectivity changes between participants with a history of depression and those without.

Result

Various pathways that differed between pre‐HD participants, with and without history of depression, showed associations with both measures (BDI‐II and HADS‐D). These associations, shown in Figure 1, included: a negative relationship between left putamen self‐connectivity and clinical cut‐offs for both measures for those with history of depression, whereas this was a positive relationship for those without history of depression; a negative relationship between left caudate self‐connectivity and both measures for pre‐HD participants with a history of depression; a negative relationship between right putamen self‐connectivity and both measures for pre‐HD participants without a history of depression.

Conclusion

Patterns in effectivity connectivity changes in association with state measures of depressive symptoms differed between pre‐HD people with or without a previous history of depression. This is the first study, to our knowledge, that demonstrates a relationship between depression and the effective connectivity of the striatum and DMN in premanifest HD. These findings suggest that large scale network dysfunction contributes to the expression of depression in Huntington’s disease.
Objective Sleep and Circadian Rest‐Activity Rhythms and Multiple Domains of Cognitive Function in Older Men and Women
Authors: Stone Katie L , Barnes Haley , Blackwell Terri , Glynn Nancy W. , Esser Karyn , Kritchevsky Stephen B , Cummings Steve , Newman Anne B , Cawthon Peggy
Published: December 2023

Background

Emerging evidence from experimental and epidemiologic studies suggests that sleep and circadian rest‐activity rhythms (RAR) play a key role in dementia and Alzheimer Disease (AD) pathology. Studies with objective measures of sleep and RAR and multiple domains of cognition in older adults remain limited.

Method

We studied 820 older men and women enrolled in the Study of Muscle, Mobility, and Aging (SOMMA), a unique cohort designed to study the cellular biology of aging and related loss of mobility. In this initial cross‐sectional analysis, participants wore wrist actigraphs for a mean of 8.0 consecutive days; recordings were processed for traditional sleep‐wake measures including total sleep time (TST) and sleep efficiency (SE); as well as parametric (acrophase, pseudo‐F) and non‐parametric (interdaily stability [IS], intradaily variability [IV], and relative amplitude [RA]) 24‐hour RAR variables. Measures of cognitive function included global cognition (the Montreal Cognitive Assessment), executive function (Trails B test), memory (California Verbal Learning Test‐short form; and psychomotor performance (Digit‐Symbol Coding Test). In models adjusted for age, sex, clinic site and education, we examined adjusted mean cognitive test scores by quartiles or categories of sleep and RAR exposures.

Result

Mean age of the cohort was 76 years, 58% were female, and 15% were non‐white. Mean TST and SE were 6.9 hours and 85%, respectively. Higher RA, reflecting a more robust 24‐hour RAR, was associated with better cognition on all tests (p for trend <0.05). The association of higher pseudo‐F, a parametric measure or robustness of RAR, to cognition was limited to psychomotor performance (p<0.03). Better psychomotor performance was also related to higher IS (consistency of RAR across days); whereas those with delayed timing (acrophase) had worse psychomotor performance (p<.0006). Lower SE was related to worse cognitive function (psychomotor performance, global cognition, memory; p<.05). There were no associations between TST and any cognitive measures.

Conclusion

SE and RAR were variably associated with both global and specific domains of cognition in older men and women. The RA in particular was strongly related to multiple domains of cognition related to AD, and may be useful in identifying individuals at risk. Additional analyses will explore gender differences and longitudinal associations.
Prevalence of Alzheimer’s dementia in the 50 U.S. states and 3142 counties: A population estimate using the 2020 bridged‐race postcensal from the National Center for Health Statistics
Authors: Dhana Klodian , Beck Todd , Desai Pankaja , Wilson Robert S. , Evans Denis A , Rajan Kumar B
Published: December 2023

Background

Estimating the prevalence and number of people with Alzheimer’s dementia in 50 U.S. states and 3142 counties can provide a better understanding of region‐specific disease burden.

Method

We utilized cognitive data from the Chicago Health and Aging Project (CHAP), a population‐based study, and combined it with the National Center for Health Statistics (NHCS) 2020 bridged‐race population estimates and determined the state‐ and county‐specific prevalence of Alzheimer’s dementia for adults 65 years and older.

Result

A higher prevalence of Alzheimer’s dementia was estimated in the East and Southeastern regions of the U.S., with the highest in Maryland (12.9%), New York (12.7%), Mississippi (12.5%), and Florida (12.5%). California and Illinois were also among the 10 states with a higher prevalence of Alzheimer’s. U.S. states. California had the highest number of people with Alzheimer’s dementia, with 719.7 (95%CI 665.0, 774.4) thousand, Texas with 579.9 (95%CI 539.9, 620.0) thousand, and Florida with 459.3 (95%CI 422.7, 496.0) thousand. The top 3 counties with the highest prevalence, 16.6%, respectively, were Miami‐Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York

Conclusion

The state‐ and county‐specific estimates could help public health officials to understand the burden of disease (e.g., demand for caregiver counseling and institutional care) and develop strategies for identifying and caring for people with Alzheimer’s dementia
Subjective cognitive impairment score associate with regional amyloid burden and brain atrophy in subjective cognitive decline subjects
Authors: Lee Chonghwee , Yang Dong Won , Hong Yun Jeong , Ho SeongHee , Jeong Jee Hyang , Park Kee Hyung , Kim SangYun , Wang Min Jeong , Choi Seong Hye
Published: December 2023

Background

Subjective cognitive decline (SCD) is now regarded as the first preclinical stage of Alzheimer’s disease (AD) spectrum disorders. It is important to predict which patients would progress to dementia, and screening tools might be helpful. In this study, we aimed to investigate the possible correlations between AD biomarkers‐regional amyloid burden and volume changes‐and Korean Dementia Screening Questionnaire‐Cognition (KDSQ‐C) score in SCD.

Method

This study analyzed SCD data from prospective population cohort study from July 2018 to December 2020. Brain magnetic resonance imaging (MRI) volumetry, visual and standardized uptake value ratio (SUVR) analysis of 18F‐Florbetaben brain amyloid Positron Emission Tomography (PET) were performed. Demographics, physical data, social and physiological functions were also obtained.

KDSQ‐C was administered to SCD subjects as part of the clinical evaluation at the 36 month follow‐up visit. KDSQ‐C included 15 questions that assess 3 dimensions: memory impairment (items 1‐5), other cognitive impairments including language impairments (items 6‐10), and the ability to perform complex tasks in daily life (items 11‐15).

Result

Prevalence of subjective cognitive impairment (KDSQ‐C ≧6) among 86 subjects was 73.3%.. No significant difference was observed between groups in terms of demographic characteristics including age, sex and APOE Ɛ4 status and neuropsychological test. However, regional SUVR (amygdala, inferior temporal gyrus and precuneus) and global SUVR were significantly higher in subjectively cognitive impaired group(p<0.05). There were no brain volume differences between groups.

For volumetry and KDSQ‐C correlation analysis, partial correlation analysis controlled for age, sex and APOE Ɛ4 status showed significant negative correlation between left entorhinal cortex, right hippocampal volume and KDSQ‐C (r = ‐0.230, p = 0.046; r = ‐0.226, p = 0.049). Similar association was also found between KDSQ‐C memory domain score and brain volume.

Conclusion

KDSQ‐C can be a useful tool for screening SCD patients at a higher risk with higher amyloid deposition and brain atrophy.

This study was supported by a grant from the Ministry of Health and Welfare, HI18C0530
Tau pathology in P301S PS19 mice alters peripheral and cerebral metabolism, sleep, and excitability
Authors: Irmen Riley E , Carroll Caitlin M , Snipes James A , Sink Sandy A , Macauley Shannon L
Published: December 2023

Background

Two biomarkers for Alzheimer’s disease (AD) are amyloid‐beta (Aβ) and tau aggregation. AD patients often experience comorbidities like metabolic dysfunction and/or sleep‐wake cycle disruption, but it is unclear whether this can be directly linked to Aβ or tau aggregation. Previous research shows mouse models overexpressing Aβ also experience metabolic and sleep dysfunction, independent of comorbidities like type‐2‐diabetes. Our lab previously demonstrated that central and peripheral metabolic changes are linked. This bidirectional relationship is well described in mouse models of Aβ overexpression; however, this relationship is relatively unexplored in mouse models of tauopathy. Therefore, our lab is investigating how central and peripheral metabolism relate to sleep‐wake disruption in the P301S PS19 mouse.

Method

To investigate changes in peripheral metabolism, body weights are measured, and glucose tolerance tests are conducted on P301S PS19 and wild type female mice. Blood glucose levels are taken after fasting for four hours. Next, the mice are given an ip dose of 2g/kg glucose followed by blood glucose measurements in 15‐minute increments for two hours. Paired glucose and lactate biosensors placed within the mouse hippocampus track second by second metabolic fluctuations over three circadian days. Along with biosensors, EEG and EMG electrodes are positioned to record sleep‐wake cycles during this period. All methods completed on 3‐, 6‐, and 9‐month‐old P301S and wild type female mice.

Result

While current experiments are ongoing, P301S mice become glucose sensitive where WT mice become glucose intolerant with age. Early analysis suggests pathology and age‐related differences in metabolism and sleep also develop over the circadian day. Our data suggests that tau aggregation increases peripheral glucose metabolism, in a manner different than Aβ pathology. Tau pathology disrupts normal sleep patterns where it decreases time spent in NREM and REM and alters EEG frequencies like delta, beta, and gamma. As age and pathology progress, cerebral metabolism of glucose and lactate is increased compared to age‐matched WT mice.

Conclusion

We hypothesize tau pathology induced hyperexcitability alters sleep/wake cycles, peripheral and cerebral metabolism, and exacerbates pathology. Our current research is valuable in expanding knowledge of the relationship between metabolism, sleep, and tau in Alzheimer’s disease.
The Maintain Your Brain online multidomain intervention for dementia risk reduction: end‐user evaluations of what did and did not work and why
Authors: Casey Anne‐Nicole S. , Chau Tiffany , Heffernan Megan , Brodaty Henry
Published: December 2023

Background

Dementia prevalence is increasing, and risk reduction is a priority. Online interventions that are useable and acceptable to people seeking to reduce their dementia risk are needed. We aimed to assess and explore end‐user perceptions of a large‐scale multidomain online intervention targeting modifiable lifestyle risk factors for dementia.

Method

Mixed methods evaluation involving Maintain Your Brain (MYB) randomised controlled trial participants 55‐77 years of age at baseline who engaged in assessments, brain training, nutrition and physical activity, and mental health modules across three years. Of 5,260 participants invited, 2,386 completed online surveys at trial conclusion of whom 1,589 offered free‐text comments. Of survey respondents, 248 agreed to be contacted for interviews, 70 were invited and 40 were interviewed. Survey respondents rated ease of use and overall experience with MYB, endorsed whether they would recommend MYB, and provided comments. Interview completers further rated satisfaction with support, expressed online or face‐to‐face setting preference, answered open‐ended questions about participation, activities and modules, and provided further comments. Data were summarised using descriptive statistics and explored using multiple qualitative methods.

Result

Respondents found computer‐based activities easy to use (92.2%), were satisfied with their overall experience (87.4%) and would recommend MYB (82.7%). Survey free‐text and interview comments addressed topics including computer literacy, health literacy, resource access, motivations, expectations, social relationships, and significant events. Perspectives on activities and information varied. Many enjoyed and/or appreciated the challenge of completing activities and assessments and the potential for health benefits from these activities. Others were disappointed by their own performance in activities and assessments, found testing and reporting repetitious, stressful and/or time‐consuming, and found educational information unhelpful. Many respondents would have preferred to access applications on phones or tablet devices and suggested that interventions should be available across platforms. Respondents wanted researchers to know that flexible and adaptive individually tailored goals and activities and timely feedback are important.

Conclusion

The MYB online multidomain dementia risk reduction program was useable and acceptable. Similar programs should be accessible, well‐supported, cross‐IT platforms, and incorporate adaptive, individually tailored activities and feedback that is responsive to the varied and changing needs of older adults.
Pathogenic characteristics of genetically modified cells with TREM2 T44A mutation
Authors: Kim Danyeong , Shim Kyu Hwan , Yang Hyewon , Bae Heewon , Kang Min Ju , Shin Seunghwan , Kim Jongsung , Yun Kyusik , Jang Chang‐Hyun , An Seong Soo
Published: December 2023

Background

Triggering Receptor Expressed on Myeloid Cells‐2 (TREM2) is known as a risk gene for Alzheimer’s disease (AD). and affect AD pathogenesis through beta‐amyloid (Aβ)‐related neuroinflammations and phagocytosis. TREM2 R47H mutation was the first reported from an AD patient in 2013. Although the TREM2 R47H variant was revealed to increase the risk of AD by three times, further mutations still need to study. Here, we found TREM2 T44A mutation from a patient of a 65‐year‐old AD patient. In order to confirm the pathogenicity of TREM2 T44A, the genetically modified cells were produced and investigated the association of the TREM2 gene with Aβ‐related pathology.

Method

TREM2 Wild type (WT) and T44A were transfected onto the HEK 293, SHSY5Y, U87 cells by using a plasmid transfection system and selected using geneticin (G418). Gene expression and TREM2 protein was measured. For measuring Aβ uptakes, Aβ was measured after incubation with cells. Cell phagocytosis was conducted with treating pHrodo labeled with Aβ and obtained cell images and video.

Result

TREM2 gene was overexpressed in transfected cells and TREM2 protein was elevated, but TREM2 T44A lowered compared to WT. TREM2 T44A showed higher Aβ42/40 ratio, with increasing extracellular Aβ42. The Aβ42 uptake were relatively lowered than TREM2 WT. Through images and video, TREM2 T44A showed lower red fluorescence than WT, but similar to MOCK.

Conclusion

In this study, we transfected TREM2 WT and T44A in a variety of cell lines (HEK 293, SHSY5Y, U87) to investigate the pathogenicity of TREM2 T44A. TREM2 T44A was shown to increase extracellular Aβ42 and decrease Aβ42 uptake. This suggests that the Aβ uptake and elimination function of TREM2 was loosed by the mutation, and therefore Aβ was not completely removed, resulting in a slight increase in extracellular Aβ in the mutant cell. The loss of the Aβ uptake correlated with confocal and video results, the red fluorescence signals were decreased in TREM2 T44A, suggesting relatively lower Aβ phagocytosis. Thus, Aβ phagocytosis was inhibited by TREM2 mutation, and the lowered Aβ uptake could not clear it, suggesting that Aβ growth and accumulation may influence the pathogenicity of AD.
The relationship between sleep duration and cortical sulcal width in midlife and older adults
Authors: Faucher Caroline , Borne Léonie , Paton Bryan , Giorgio Joseph , Fripp Jurgen , Thienel Renate , Lupton Michelle K , Breakspear Michael
Published: December 2023

Background

Emerging evidence suggests that poor sleep is associated with worse cognitive and structural brain health, and an increased risk of developing dementia (Bubu et al., 2016; Fjell et al., 2022; Tai et al., 2022). The present study investigated the influence of sleep duration on the cognition‐brain relationship in older adults using sulcal width (SW), a reliable measure of changes in the ageing brain (Bertoux et al., 2019). The influence of napping, depression likelihood, and genetic risk for dementia (APOE ε4 status) was also explored.

Method

Participants were 137 cognitively normal adults, aged 46‐72 from the Prospective Imaging Study of Ageing (PISA). Demographic information, sleep duration, and depressive symptoms were collected via online questionnaires. Cognition was assessed using the Cambridge Brain Systems battery. APOE genotype was determined from blood‐extracted DNA. Imaging data was acquired using a 3T Siemens PRISMA scanner. SW was extracted using the Morphologist pipeline (Borne et al., 2020).

Canonical Partial Least Squares (PLS) were used to obtain latent variables of cognition and SW. ANCOVAs measured the effect of sleep duration categories (7‐7.5 hours versus {<7 or ≥8 hours}) on the cognitive and SW components, with sex and age as covariates. Status of depression likelihood was added as a covariate of interest. The effect of napping, and APOE ɛ4 allele on these same components were measured by ANCOVAs, with sex and age as covariates.

Result

We observed a significant effect of sleep duration on SW (F(1, 133) = 4.17, p = 0.043, Fig. 1). This effect remained significant (F(1,132) = 4.89, p = 0.029) after including depression likelihood as a covariate, which was also significant in the model (F(1,132) = 4.62, p = 0.034). A significant interaction between APOE ε4 status and age (p = 0.050) on SW was also observed.

Conclusion

Results add weight to studies suggesting that not too much or too little sleep is needed to maintain brain health in later life (Li et al., 2022; Liang et al., 2019). Depression, a risk factor for dementia (Livingston et al., 2020), was also associated with poorer brain health. Results suggest that at approximately 60 years of age, the influence of a positive APOE ε4 status is associated with increasing age‐related brain atrophy.
Diagnosis of Severity of Alzheimer’s Disease from Clinical notes in the Veterans Affairs Healthcare System
Authors: Aguilar Byron J. , Shishova Ekaterina , Li Xuyang , Nguyen Andrew H. , Morin Peter J , Berlowitz Dan , O'Connor Maureen K. , Miller Donald R , Jasuja Guneet , Zhang Raymond , Monfared Amir Abbas Tahami , Zhang Quanwu , Xia Weiming
Published: December 2023

Background

Alzheimer’s disease (AD) typically progresses in three stages: mild, moderate, and severe. Early detection improves patient care related to identification of suitable interventions and end‐of‐life planning. However, AD severity diagnosis is uncommon. The aim of this study is to identify Veterans in various stages of AD using clinical notes in the Veterans Affairs Healthcare System.

Method

Notes containing “Alz*” from fiscal year 2019 were identified then screened for information indicating a clinical diagnosis of probable AD. Screened notes with AD severity keywords (mild, moderate, severe, early, late, advanced) within four words of “Alz*” were considered as a severity diagnosis. Notes containing a single AD severity diagnosis were included in the study.

Result

141,816 Veterans with 547,318 notes containing “Alz*” were identified as probable AD cases. Roughly 9% of notes contained at least one severity keyword and 6% of notes contained a single severity keyword. 34,181 notes with a single severity keyword from 14,148 Veterans were included in this study. The cohort comprised of 96% males and 78% identified as White with a mean age of 79. Ten percent of Veterans with an AD note included severity diagnosis. Approximately 19%, 12%, 18%, 20%, 3%, and 28% of severity notes contained mild, moderate, severe, early, late, and advanced, respectively. The mean age for Veterans with a mild, moderate, or severe AD diagnosis increased from 78 to 81. The mean age for early, late, and advanced AD patients increased from 74, 79, and 81, respectively. AD severity diagnosis was found in notes related to primary care (11%), internal medicine (10%), psychiatry (8%), mental health (7%), neurology (6%), geriatric (5%), neuropsychology (1%), and psychology (1%).

Conclusion

AD severity diagnosis is uncommon. Identification of patients in various stages of AD will lead to a better understanding of transition from one severity to another and facilitate the coordination of services to improve patient care. Specifically, identification of AD patients in the early stage may identify candidates for novel therapeutics focused on delaying AD progression.
Selective vulnerability of the suprachiasmatic nucleus in progressive Alzheimer’s Disease: A human postmortem study using spatial in‐situ proteomics
Authors: Son Gowoon , Mladinov Mihovil , Pereira Felipe Luiz , Tu Chia‐Ling , Li Song Hua , Suemoto Claudia Kimie , Leite Renata Elaine Paraizo , Paes Vitor Ribeiro , Pasquallucci Carlos Augusto , Jacob‐Filho Wilson , Spina Salvatore , Seeley William W. , Chang Wenhan , Neylan Thomas C. , Grinberg Lea T.
Published: December 2023

Background

Alzheimer’s Disease (AD) patients commonly experience sleep/wake (S/W) disturbances, such as sleep fragmentation and excessive daytime sleepiness. The S/W cycle is controlled by a complex system regulated by a master regulator, the suprachiasmatic nucleus (SCN) that controls wake‐ and sleep‐promoting nuclei. Despite its importance in orchestrating sleep architecture, little is known about the molecular changes that occur in the SCN during the progression of AD and how these changes contribute to S/W disturbances.

Method

We used postmortem brain tissue of 10 controls without AD pathology and 32 subjects with progressive AD stages. Our approach included quantitative neuropathological assessments of AVP and VIP‐expressing neurons in SCN and its adjacent hypothalamic region, the supraoptic nucleus (SON). We also used an in‐situ cell‐specific spatial proteomics platform [GeoMx Digital Spatial Profiling (DSP)] to probe levels of different pathological tau species and proteins commonly dysregulated in AD.

Result

Preliminary findings reveal a significant decrease in SCN volume (∼75%) (Fig.1) and a loss of ∼58% AVP neurons and ∼41% VIP neurons in Braak stage (Braak) VI compared to Braak 0. The DSP results indicate that both neurons in the SCN have twice the burden of p‐tau levels as the SON (Fig.2‐right), and neurofibrillary tanglesAdditionally, SCN shows an increase in proteins associated with glia and immune responses (Fig.2‐left). Furthermore, an increase in microglial proteins is observed in the SCN in Braak I (Fig.3‐left). In contrast, the SON displays a milder pattern of protein dysregulation in Braak I (Fig.3‐right), consistent with its lower tau expression observed in histology and DSP.

Conclusion

SCN is vulnerable to AD pathology even in Braak I, which is characterized by volume loss, increased immune response protein dysregulation, and later neuronal loss, as well as p‐tau pathology. This pattern supports the idea that the SCN plays a role in S/W disturbances observed from early AD stages. Interestingly, its neighboring nucleus, SON, which also has AVP neurons, remained spared, providing opportunities for studies investigating factors related to selective vulnerability. Ongoing studies are addressing changes in the SCN and SON in intermediate AD stages.
The association of childhood socio‐economic position with later life brain structure in individuals of Hispanic/Latino background. Preliminary results from the INCA‐MRI study
Authors: Isasi Carmen R , Filigrana Paola , Moon Jee‐Young , Lipton Richard B. , Gallo Linda C , Kaplan Robert , Daviglus Martha L , Testai Fenando D , Marquine Maria J. , Cai Jianwen , Schneiderman Neil , Perreira Krista M , Stickel Ariana M , González Hector M , Decarli Charles
Published: December 2023

Background

Childhood is a period of brain plasticity when environmental influences may have long‐lasting effects. Early socio‐economic position (SEP) may influence brain development at vulnerable stages and set the stage for increased vulnerability to Alzheimer’s Disease and related dementias (ADRD). In this study, we evaluated whether childhood SEP was related to brain structure in adulthood.

Methods

This analysis included the first 1320 individuals (61% women, age range 50‐85) of diverse Hispanic/Latino background with brain magnetic resonance imaging (MRI) assessments from the HCHS/SOL INCA‐MRI study, conducted at four major urban areas (Bronx, NY; Chicago, IL; Miami, FL, and San Diego, CA). Childhood SEP was assessed by self‐reported maternal educational achievement. We also calculated the difference between attained height and genetically predicted height using height‐associated SNPs, sex, and genetic ancestry as a biomarker of early environmental exposures. Positive values indicate taller attained stature than the expected based on SNPs, suggesting favorable early environmental influence on height; negative values suggest environmental conditions limiting growth. Measures of brain structure [total intracranial volume (TICV), total gray matter volume (TGMV) and hippocampus volume (HV)] were obtained using MRI with standardized procedures. Survey linear regression models were conducted adjusting for potential confounders.

Results

Low parental educational achievement was common, 55% of mothers completed less than a middle school education. In multivariable linear regression models, higher maternal educational achievement was associated with some measures of brain structure, such as greater TICV (b = 18.6, p<.001 for high school (HS) graduate; b = 26.2, p<.01 for > HS; reference <6 grade), higher TGMV (b = 5.8, p<.02 for HS graduate; b = 5.4, p<.10 for > HS), and higher HV (b = 0.14, p<.01 for HS graduate; b = 0.03, p = NS for greater than HS). Early life factors affecting height were associated with lower TICV (b = ‐18.9, p<.001), lower TGMV (b = ‐6.4, p<.001), and lower HV (b = ‐0.6, p<.01).

Conclusion

This study showed associations of early childhood socio‐economic position with brain structure assessed in later adulthood. Findings suggest that height residual is a useful predictor of early life environment affecting later life brain volumes.
Association of gabapentin and neuropathological hallmarks in an autopsy cohort of older adults
Authors: Oh GYeon , Moga Daniela C , Fardo David W. , Harp Jordan P. , Abner Erin L
Published: December 2023

Background

Previous studies of the association between gabapentin use and neurocognitive change have shown conflicting results. We examined the association between end‐of‐life gabapentin use and neuropathological features in older adults using National Alzheimer’s Coordinating Center Uniform Data Set and Neuropathology Data Set (9/2005‐3/2022).

Methods

We conducted a cross‐sectional study including participants with at least one visit within two years before autopsy and age at visit 65+ years. Gabapentin use was determined based on the two‐year window. Outcomes of interest included burden of tau (Braak stage), amyloid (Thal stage, diffuse plaques, and neuritic plaques), α‐synuclein (Lewy bodies), cerebrovascular disease (infarcts, microinfarcts, and arteriosclerosis), hippocampal sclerosis, cerebral amyloid angiopathy, TDP‐43, and atrophy (cerebral cortex and hippocampus). Collection of Thal stage, TDP‐43, and atrophy information occurred after January 2014; these outcomes were assessed in the subset with data. For each dependent neuropathological hallmark, two models were constructed (M1: adjusted for age, sex, APOE, center, and cognitive status; M2: adjusted for M1 confounders, agitation, depression, antiseizure drug, and use of opioids). To mitigate bias, joint stabilized inverse probability of treatment and censoring weights were used.

Results

We included 213 gabapentin‐users (mean age[SD]: 80.9[8.7]; male 53.5%) and 4107 non‐users (82.0[8.7]; 54.7%). Gabapentin use was associated with reduced odds of Braak stage IV‐VI vs. 0‐III, moderate/frequent vs. non/sparse diffuse plaques, presence of Lewy bodies, infarct, and cerebral amyloid angiopathy in M1 and M2, and hippocampal sclerosis in M1 (Figures 1A and 1B). For the subset outcomes, 116 gabapentin‐users (mean age [SD]: 81.0 [8.6]; male 50.9%) and 1919 non‐users (81.8 [8.9]; 54.3%) were included. Gabapentin use was associated with increased odds of Thal phase 3‐5 vs. 0‐2 in M1 and M2, and amygdala TDP‐43, hippocampus TDP‐43, and cerebral cortex atrophy in M2; whereas gabapentin use was associated with decreased odds of hippocampus atrophy in M1 and M2, and amygdala TDP‐43, hippocampus TDP‐43, and cerebral cortex atrophy in M1 (Figures 1C and 1D).

Conclusion

End‐of‐life gabapentin use was not significantly associated with burden of neuropathologic features and there were no clear patterns. Further studies with increased sample sizes and better measurement of gabapentin use are needed.
Types of social support and depressive symptoms in older adults: An IPD meta‐analysis of longitudinal ageing studies
Authors: Samtani Suraj , Mahalingam Gowsaly , Lam Ben C. P. , Lipnicki Darren M. , Costa Erico , Lima‐Costa Maria Fernanda , Xiao Shifu , Scarmeas Nikolaos , Kim Ki Woong , Numbers Katya T. , Ganguli Mary , Krishna Murali , Ng Tze Pin , Sachdev Perminder S. , Brodaty Henry , Skoog Ingmar , Riedel‐Heller Steffi G. , Shahar Suzana ,   COSMIC consortium and SHARED consortium
Published: December 2023

Background

Depression is a known risk factor for dementia, and social support may lower the risk of depression in older adults. There is, however, a lack of longitudinal analyses examining the association between emotional versus instrumental support and depressive symptoms in older adults. We analyzed the association of emotional and instrumental support with depression symptom scores using data from eight international longitudinal cohorts. This is an individual participant data meta‐analysis on harmonized social support and depression data.

Method

We obtained data from eleven COSMIC (Cohort Studies of Memory in an International Consortium) international longitudinal cognitive ageing studies, including data from Australia, Brazil, China, Germany, Greece, India, Indonesia, South Korea, Singapore, Sweden, and the United States. Randomly sampled 27,058 adults in later life (M = 71.7 years), of whom 59.5% were females. Social support was measured using individual items of emotional support (i.e., having a confidante) or instrumental support (i.e., help with daily living activities). Depression was measured using validated scales at baseline and follow‐up (M = 2.02 years). Covariates included age, sex, education, living situation, smoking history, diabetes mellitus, cardiovascular risk, global cognitive function and (where available) history of depression. Depression scores were standardized while other variables were harmonized before analysis.

Result

In the fully adjusted cross‐sectional models, having emotional support (B = ‐0.40, 95%CI: ‐0.60,‐0.21), but not instrument support (B = 0.15, 95%CI: ‐0.29,0.58) was associated with lower depressive symptoms. In the fully adjusted longitudinal models, having emotional support (B = ‐0.36, 95%CI: ‐0.53,‐0.19) but not having instrumental support (B = 0.07, 95%CI: ‐0.33,0.46) was associated with lower depressive symptoms at follow‐up.

Conclusion

Emotional, but not instrumental support, was associated with lower depressive symptoms cross‐sectionally and at follow‐up in harmonised data from 8 longitudinal ageing studies. Psychosocial interventions targeted at reducing the risk of depression (and therefore dementia) should focus on improving access to emotional support for older adults.
Effectiveness of oral health education in enhancing oral care knowledge,attitudesand behaviors for family caregivers of persons with dementia
Authors: Chien Chen‐Yi , Hu Yu‐Chen , Huang Huei‐Ling , Hsieh Shu‐Hua , Chiu Ying‐Chi , Su Pei‐Yin
Published: December 2023

Background

Due to the loss of cognitive function and memory, persons with dementia gradually lose their self‐care and social skills, and the weakening of their oral care ability can easily lead to periodontal disease, dry mouth, and root caries. Studies have shown that oral health maintenance can help prevent dementia and delay functional deterioration. Therefore, it is important to provide oral hygiene guidance to family caregivers to improve the quality of oral health care for persons with dementia.

Oral care questionnaires and oral health assessment scales were used to assess the knowledge, attitude and behavior of family caregivers towards oral care for the person with dementia. Based on the assessment results, an oral health education program was designed, including: 1. immediate oral care health education at the outpatient clinic; 2. mailing of dementia oral care health education leaflets; and 3. individual health education and discussion by telephone one week after mailing. A post‐test was conducted one week after the intervention to evaluate the effectiveness of the program.

Results

Family caregivers' oral care knowledge correctness increased from 49% to 88.9%, attitude correctness increased from 29% to 71.45%, and behavior correctness increased from 84% to 100%.

Conclusion

The results showed that a multicomponent oral health education program could improve the oral care knowledge, attitude, and behavior for family caregivers of persons with dementia. In particular, the use of telephone health education and assessment during the COVID‐19 epidemic may provide a reference.
Non‐AD pathologies, as measured using a mismatch index between regional brain metabolism and tau PET signal, are associated with age, sex, and amyloid burden.
Authors: Malotaux Vincent , Colmant Lise , Dricot Laurence , Quenon Lisa , Huyghe Lara , Gérard Thomas , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard J
Published: December 2023

Background

Brain hypometabolism in the absence of tauopathy may indicate the presence of non‐AD pathologies. We aimed to investigate the mismatch between regional tau pathology and brain metabolism to characterize the profile of patients suspected to have co‐pathologies.

Method

Sixty‐one clinically impaired patients, attending the Memory Clinic, performed both a [18F]‐Fluorodeoxyglucose‐PET to assess brain metabolism and a [18F]‐MK6240 Tau‐PET to estimate tau burden. To compare these images, we normalized them using data from clinically normal older adults (n = 30), resulting in FDG and tau z‐scores for 74 FreeSurfer‐defined regions. We computed intra‐subject correlation coefficients between tau and FDG data as a mismatch index between tau and metabolism. We then compared FDG and tau z‐scores using intra‐individual paired sampled t‐tests and identified patients with hypometabolism exceeding tau pathology (suspecting co‐pathologies). To increase sensitivity, the same analysis was repeated using temporal regions only. We finally evaluated demographics, cognition, and amyloid burden in the group of patients with suspected co‐pathologies.

Results

In the entire cohort, the intra‐subject FDG‐Tau correlation was significantly negative in the temporal lobe (r = ‐0.27, p<0.05), but not in the entire neocortex (r = ‐0.11), demonstrating closer association between modalities in the temporal lobe, and greater mismatch in the other regions. Twenty‐five (41%) patients had significantly greater FDG z‐scores than tau z‐scores, including thirteen (21%) with greater hypometabolism than tau pathology in the temporal lobe. These patients were older and more frequently male than patients with greater tau pathology; those with a temporal mismatch also had lower amyloid pathology (Table 1). Older ages and better cognition were associated with the mismatch index in the entire neocortex (r = 0.25/0.49, p<0.05); in addition, lower amyloid burden was associated with the temporal mismatch index (r = 0.27, p<0.05, Fig.1).

Conclusion

Patients with greater temporal hypometabolism than tau deposition are older, more frequently males, and have lower amyloid burden than patients with greater temporal tau deposition. These patients are suspected to have temporal non‐AD pathologies.
Moving Pictures India: Co‐designing a digital dementia care intervention for low and middle income countries
Authors: Brijnath Bianca , Rao Rachita , Antoniades Josefine , Baruah Upasana , Loganathan Santosh , Varghese Mathew , Cooper Claudia , Kent Mike , Dow Briony
Published: December 2023

Background

Despite the rapid proliferation of smartphones in low and middle‐income countries (LMICs), few studies have explored how to harness this technology to improve dementia care. Using a case‐study from India, where 830 million people are smartphone users, we describe the co‐design of a fully digitalised dementia care intervention for family carers in a resource‐poor setting.

Method

Qualitative in‐depth video interviews were conducted in English, Hindi, and/or Kannada with 19 family carers and 25 health providers in Bangalore, India. Data were thematically analysed, then presented to 10 of the interview participants in a co‐design workshop, where they were asked to storyboard the data to form the basis of nine short films on dementia care.

Result

Workshop participants developed storyboards for nine films: signs of dementia and the diagnostic process; first steps and treatment; managing difficult behaviours; working with doctors and going to hospital; managing pain; eating, nutrition, and dental care; managing hygiene and incontinence; later stages and palliative care; and self‐care for carers. A proposed film on care pathways was deemed too broad and discarded. Instead, carers wanted greater specificity on routine, sleep, and pleasant activities as well as legal and ethical issues in dementia care. Overall, 11 films were proposed. Carers used the parent‐child analogy to describe their relationship with the person with dementia, utilised various surveillance technologies to keep their relative safe, and expressed differing views about institutionalised care. These cultural nuances and systemic issues associated with care will be reflected in the films. Once produced, the films will be member checked with all interview participants and community members for cultural salience and relevance before progressing to a full digital trial to evaluate its impact on reducing carer burden and improving carer’s mood and quality of life.

Conclusion

The films will be available on a mobile‐optimised website, freely accessible, and bypass barriers of distance, being time‐poor, and semi‐literate. By co‐producing resources in country, this model is scalable, based on knowledge of local resources and burden of disease, and relevant to LMICs where substantive increases in dementia prevalence are anticipated to occur.
Cognitive reserve in Down syndrome: a new opportunity to understand resilience in Alzheimer’s disease
Authors: Vaqué‐Alcázar Lídia , Carmona‐Iragui Maria , Videla Laura , Barroeta Isabel , Benejam Bessy , Rodríguez‐Baz Íñigo , Arranz Javier , Pegueroles Jordi , Lleó Alberto , Fortea Juan , Bartrés‐Faz David
Published: December 2023

Background

Traditionally, cognitive reserve (CR) and other related concepts underlying resilience, have been studied in the context of aging and Alzheimer’s disease (AD; Stern et al., 2020). Despite the increasing interest in elucidating how CR measures influence brain and cognitive development through a lifespan perspective (Kremen et al., 2019), its study in developmental diseases such as Down syndrome (DS) remains unexplored. Understanding the role of CR and its neurobiological mechanisms in DS is critical, since this population is genetically determined to develop AD (Fortea et al., 2021). During the last decades, people with DS have experienced an improvement in the number and quality of stimulating activities due to the higher inversions in disability services and community support resources. In this regard, our goal was to test whether this enriched environment would result in a generational effect showing a lower intellectual disability (ID) level and a higher intellectual profile as function of the birth year in DS.

Method

We selected a cross‐sectional subsample from the cohort study of adults with DS recruited at the Alzheimer‐Down Unit from the Catalan Down Syndrome Foundation and Hospital of Sant Pau. We included 528 participants with DS without clinical symptoms of AD born between 1955‐1995 (age: 39.25±9.27 years; 46.02% females). Participants with profound ID (as these individuals perform at floor scores) were excluded for Kaufman Brief Intelligence Test (K‐BIT) analyses (N = 379; age: 39.03±9.10 years; 48.02% females).

Result

Results evidenced a generational increase in the proportion of individuals with mild or moderate ID and a decrease in those with profound or severe ID level (Fig1). Similarly, a higher proportion of individuals acquired intellectual milestones (i.e., language, literacy, calculation; Fig2). Furthermore, our analyses revealed an increase in mean K‐BIT scores as function of the birth year (P<.001; Fig3).

Conclusion

There have been major changes in CR proxies in individuals with DS. Given the near full penetrance of AD in this population, characterizing the effect of these factors on AD presentation and pathophysiology could signify an important advance in the design of primary prevention plans in this particularly vulnerable population, which could probably be transferred to the general population.
The Effects of Moderate and High Intensity Aerobic Exercise on Lipid and Lipoprotein Metabolism and Brain Volume in Cognitively Normal Older Australians: Data from the IPAC Study
Authors: Kadyrov Maria , Whiley Luke , Erickson Kirk I. , Holmes Elaine , Brown Belinda M
Published: December 2023

Background

A common misconception about ageing is that a decline in brain health is solely observed in those who have dementia. In fact, decreases in cognitive function and reductions in brain volume are commonly observed in adults over the age of 65. Brain changes in older adulthood have been shown to be decreased in individuals who are more physically active, with alterations in lipid and lipoprotein metabolism emerging as a potential mechanism, however this is still not well understood. In light of this, our study aims to investigate the effects of moderate and high intensity aerobic exercise on lipid and lipoprotein metabolism to assess the efficacy of exercise in reducing brain atrophy in cognitively normal older adults.

Method

Samples were collected from the Intense Physical Activity and Cognition (IPAC) study, during which a six‐month randomised controlled trial was performed to observe the impact of aerobic exercise on brain volume measurements in cognitively normal older adults (n = 99, aged 60‐80). Blood samples and neuroimaging measures were collected at baseline and following the completion of the intervention (6 months). Baseline and post‐intervention plasma samples were collected and analysed using 1H‐NMR spectroscopy to quantify 112 lipoproteins, followed by a comprehensive in‐house mass spectrometry (MS) lipids screen targeting >1200 individual lipid species.

Result

Preliminary analyses suggest that lipid and lipoprotein metabolism is altered by aerobic exercise and that these alterations are associated with changes in brain volume. Further analyses will increase the sample size, and also evaluate other factors (i.e. sex, APOE status) as potential moderators of the link between aerobic exercise and the metabolism of lipids and lipoproteins.

Conclusion

To our knowledge, this study is the first to establish the relationship between exercise and lipids and lipoprotein metabolism, and their association to brain volume in cognitively normal older adults. The significance of our findings will be evaluated further using an external validation cohort. The discovery of novel lipids or metabolic pathways will create avenues for future research into new therapeutic targets for future healthy ageing interventions.
The heritability of subjective cognitive complaints in older Australian twins
Authors: Selwood Amanda , Catts Vibeke S. , Numbers Katya T. , Lee Teresa , Thalamuthu Anbupalam , Wright Margie , Sachdev Perminder S.
Published: December 2023

Background

Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. This study aimed to examine the heritability of SCCs, and the influence of personality and mood on the relationship between SCCs and memory performance.

Method

The heritability of SCCs were examined in 306 twin pairs using structural equation modelling. Genetic, environmental, and phenotypic correlations between SCCs and memory performance, personality, and mood scores were determined.

Result

SCCs were low to moderately heritable. Mood appeared to be related to SCCs by an environmental correlation, whereas memory performance was related to SCCs by a genetic correlation. SCCs had a significant amount of both genetic and environmental variances not explained by memory performance, personality, or mood.

Conclusion

Our results suggest that SCCs are influenced both by a person’s mood and their memory performance, and that these determinants are not mutually exclusive. Much of the genetic and environmental components to SCCs were specific to SCCs, with the specific factors yet to be determined.