bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadband access may influence variation in Alzheimer’s disease and related dementias prevalence in Central Appalachia
Authors: Rajczyk Jenna , Wing Jeffrey , Burke James , Xu Wendy Yi
Published: January 2025

Background

Geographical differences in the burden of Alzheimer’s disease and related dementias (ADRD) exist in the US. Rural and Appalachian areas are characterized by limited access to primary and specialty health care in comparison to their urban and non‐Appalachian counterparts. Better access to telehealth can improve detection of ADRD in remote regions but it highly relies on availability of broadband services. Our objective is to evaluate the influence of county‐level broadband availability on Appalachian and rural variation in ADRD prevalence in Central Appalachia.

Method

County‐level ADRD prevalence among fee‐for‐service Medicare beneficiaries in Central Appalachia (Kentucky, North Carolina, Ohio, Tennessee, Virginia, and West Virginia) was estimated using 2015‐2018 Centers for Medicare and Medicaid Services Public Use Files. Broadband availability was defined as county‐level measures of broadband presence (FCC Broadband Deployment Data 2015‐2019), proportion of households with broadband, household device ownership, household internet access (American Community Survey 2015‐2019), and broadband usage (Microsoft 2019). ADRD prevalence by Appalachian Regional Commission’s Appalachian/non‐Appalachian designation, and by rural/urban classification (Rural‐Urban Continuum Codes) was estimated using sequential negative binomial regression models: (1) crude; (2) adjusted for age, education, and care access (PCP and neurology visits); (3) additionally adjusted for all broadband measures.

Result

Among all Central Appalachian counties, 52%‐97% had broadband access throughout the study period (Figures 1‐2). The proportions of urban (61%) and non‐Appalachian counties (60%) with broadband access were higher relative to rural (39%) and Appalachian (40%) counties. Appalachian counties had higher prevalence in both rural (Prevalence Ratio (PR): 1.02; 95% CI: 1.00, 1.04) and urban (PR: 1.03; 95% CI: 1.02, 1. 05) areas, but this was mostly explained by socio‐demographics in rural areas (PR: 1.00, 95% CI: 0.98, 1.02; Table). Variation in urban counties persisted after adjustments for demographics, access, and broadband (PR: 1.01; 95% CI: 1.00, 1.03).

Conclusion

Variation in ADRD prevalence was largely explained by socio‐demographics and care access but not broadband availability. However, the role of broadband access on ADRD prevalence needs to be clarified. Greater broadband access may reflect improved telemedicine access and higher diagnoses, yet the inconsistency in rural counties challenges this hypothesis and other explanations should be considered.
Tau accumulation mediates β‐amyloid effects on hippocampal atrophy and memory in early Alzheimer’s disease
Authors: Fernandez‐Lozano Sofia , Fonov Vladimir S , Therriault Joseph , Rahmouni Nesrine , Servaes Stijn , Stevenson Jenna , Poltronetti Nina Marguerita , Rosa‐Neto Pedro , Collins D Louis
Published: January 2025

Background

While we know dementia in Alzheimer’s disease (AD) results from the accumulation of β‐amyloid (Aβ), tau pathology, and hippocampus atrophy (HC), it is still unclear how these factors impose cognitive decline.

Method

We used Structural Equation Models (SEM; lavaan R package) to explore the complex relationships between the neurobiological factors in the early stages preceding AD dementia in the TRIAD cohort. Our sample comprised 333 timepoints of neuropsychological evaluation (MoCA), structural MRI, Aβ ([18F]AZD4694), and tau ([18F]MK6240) PET of cognitively healthy (NC) and mild cognitive impaired (MCI) participants. We measured neurodegeneration with an inverted HC‐to‐Ventricle ratio (HVR), i.e. 1‐HVR, an integrity measure composed of the ratio of the HC volume and the sum of the volumes of HC and the temporal horn of the lateral ventricle.

We used a feature selection algorithm (Boruta R package) to select the most important Regions of Interest (ROIs) from the CerebrA atlas relating Aβ & Tau to memory. We then used SEM to explore the mediation of Aβ and Tau on HC‐atrophy and memory using 1) the average Aβ & Tau SUVR of all ROIs and 2) separate models using the Aβ & Tau SUVR for each of the ROIs. Age, sex and education were treated as covariates. For ease of comparison, we calculated the standardized coefficients in our models.

Result

The demographic data of our sample is presented in Table 1.

The selected ROIs were: bilateral amygdala, hippocampus, and parahippocampal gyrus; right fusiform gyrus and orbitofrontal cortex (lateral and medial portions); and left middle temporal gyrus.

The full SEM with all ROIs show full mediation between Aβ, Tau and HC‐atrophy, and partial mediation between all biomarkers (Figure 1). On the distinct models by ROI, Amyloid’s effect on MoCA is almost always indirect through Tau (Figure 2).

Conclusion

We show that, even in the early stages of AD, Aβ aggregation alone has no effect on HC atrophy, and only a weak effect on cognitive decline; interactions with tau pathology is required to modulate the effects of Aβ aggregation on both HC atrophy and memory loss.
Association between autonomic function, depressive symptoms, and cognitive function in cognitively normal older adults in U.S. POINTER trial
Authors: Shaltout Hossam A , Garcia Katelyn R , Baker Laura D , Snyder Heather M , Papp Kathryn V , Bailey Margie J , Brinkley Tina E
Published: January 2025

Background

Autonomic dysfunction and depression are among the most common causes of disability in high‐income countries and depression has been associated with deficits in various cognitive domains. The degree to which depression associates with autonomic function and modifies risk for Alzheimer’s disease (AD) in older adults is unknown. We investigated the association between depression status and autonomic function measures in 398 participants enrolled in the U.S. POINTER trial (mean age: 68.0±5.3 years, 61% female, 32% people of color).

Methods

Continuous blood pressure and ECG recordings were used to assess baroreflex sensitivity (BRS), blood pressure variability (BPV), heart rate variability as measured by root mean square of successive differences (rMSSD) and standard deviation of beat to beat interval (SDNN), and sympathovagal balance (LF/HF ratio). Participants were classified as depressed if their geriatric depression scale (GDS) score was >4 or if they used antidepressants, or as non‐depressed if their GDS score was ≤4. Autonomic variables were compared according to depression status. Linear regression was used to examine cross‐sectional associations between the outcomes of interest adjusting for age, sex, race/ethnicity, education, and site.

Results

The prevalence of depression was 27% (n = 110). Depressed individuals were more likely to be female (p = 0.0021), have higher cholesterol levels (p = 0.0056), and have lower BRS (p = 0.0016), rMSSD (p = 0.009) and SDNN (p = 0.0003), with a trend for higher LF/HF ratio (p = 0.12). GDS score was negatively associated with BRS (p<0.05), rMSSD (p = 0.04), and SDNN (p = 0.008). Meanwhile, LF/HF ratio positively correlated with measures of global cognition (p = 0.0045), executive function (p = 0.003), and processing speed (p = 0.008), while rMSSD and SDNN positively correlated with the mini‐mental state examination score. SDNN positively correlated with global cognition and executive function (p<0.05). Adjusting for GDS score did not alter the association between autonomic function and cognition.

Conclusions

In this population of older adults at risk for AD, measures of autonomic function were positively associated with cognitive function and negatively associated with depression. Further studies are needed to assess if early diagnosis and treatment of depression in this population could delay the development of AD.
Beyond GWAS: Investigating Structural Variants and Their Segregation in Familial Alzheimer’s Disease
Authors: Gunasekaran Tamil Iniyan , Reyes‐Dumeyer Dolly , Corvelo André , Clarke Wayne E. , Evani Uday S. , Byrska‐Bishop Marta S. , Basile Anna O. , Runnels Alexi , Musunuri Rajeeva O. , Narzisi Giuseppe , Faber Kelley M. , Goate Alison M. , Boeve Brad F. , Cruchaga Carlos , Pericak‐Vance Margaret A. , Haines Jonathan L. , Rosenberg Roger N , Tsuang Debby W , Mejia Diones Rivera , Medrano Martin , Lantigua Rafael A. , Sweet Robert , Bennett David A. , Wilson Robert S. , Foroud Tatiana M. , Dalgard Clifton L. , Mayeux Richard , Zody Michael , Vardarajan Badri N
Published: January 2025

Background

Late‐Onset Alzheimer’s Disease (LOAD) is characterized by genetic heterogeneity and there is no single model explaining the genetic mode of inheritance. To date, more than 70 genetic loci associated with AD have been identified but they explain only a small proportion of AD heritability. Structural variants (SVs) may explain some of the missing AD heritability, and specifically, their segregation in AD families has yet to be investigated.

Method

We analyzed WGS data from 197 NHW families (926 subjects, 58.5% affected) and 214 CH families (1,340 subjects, 59.17% affected). Manta, Absinthe, and MELT were used for large insertions/deletions calling from short‐read WGS, combined with Sniffles2 calls from 4 ONT‐sequenced genomes and an external SV call set from HGSVC on 32 PacBio‐sequenced genomes from the 1000 Genomes Project. Genotyping produced a unified project‐level VCF. We identified 45,251 insertions and 76,566 deletions genome‐wide. Variants were tested for segregation and pathogenicity using Annot‐SV, cadd‐SV, and Variant Effect Predictor. Segregation required SV presence in all affected family members and only in unaffected members five years younger than average disease onset.

Result

We identified 453 insertions and 598 deletions segregating in 78.68% and 87.31% of NHW families, respectively. In CH families, 432 insertions and 460 deletions were segregating in 75.23% and 72.90% of the families, respectively. Genes overlapping with the SVs exhibited high expression levels in brain tissues. Notably, around 93% of insertions and 76% of deletions segregating in NHW and CH families were less than 1 kilobase pair (1kbp) in length. A total of 79 insertions and 96 deletions were found to be segregating in both NHW and CH families. Interestingly, a segregating insertion was observed in CH families overlapping within the CACNA2D3 gene, which was previously reported in a CH GWAS for clinical AD. A deletion segregating in NHW overlapped with the PSEN1, and another in a CH family overlapped with the PTK2B gene.

Conclusion

Our findings suggested that there are several SVs associated with familial AD across CH and NHW families. Prioritizing the SVs based on their effects on gene function and expression will be helpful in understanding their contributions in AD.
More Cumulative Time Spent Pregnant is Associated with Thicker Cerebral Cortex in Postmenopausal Women
Authors: Bramen Jennifer E. , Popa Emily S. , Kwon Dayoon , Chang Marcus , Raj Sonel , Crandall Carolyn , Espeland Mark A. , Porter Verna R. , Siddarth Prabha , Fox Molly
Published: January 2025

Background

Matrescence, like adolescence, is a critical period for neurodevelopment characterized by hormonal changes that reshape the brain in preparation for new experiences and subsequent learning. Women exhibit greater age‐matched Alzheimer’s disease (AD) risk than men, yet little is known about long‐term neurological health consequences of reproduction (Buckley, 2019), the defining biological difference between the sexes. We tested the hypothesis that greater number of months pregnant would be positively associated with cortical thickness (CT), particularly in regions within the default mode network (DMN). DMN disruption is well‐established in AD pathology (Dennis, 2014). Research also indicates that synaptic pruning within the DMN during pregnancy is related to improved maternal attachment and reduced hostility toward the infant, with these changes persisting post‐partum (Hoekzema, 2017; Garcia, 2021). Moreover, in late life, beneficial changes due to motherhood have been shown in the DMN (Orchard, 2021).

Method

We used data from 1004 older women from the Women’s Health Initiative Magnetic Resonance Imaging (MRI) study (Coker, 2009) (Table 1). CT was estimated from T1‐weighted MRI using FreeSurfer. The effect of cumulative pregnancy duration on mean CT was assessed using a linear mixed model, controlling for parity (number of complete pregnancies), breastfeeding duration, age, reproductive span, estrogen, and progestogen hormone therapies (HT) and duration, and time since HT cessation. Cortical surface analyses used linear regression, accounting for the same confounders, and were corrected for multiple comparisons using cluster‐wise probability.

Results

The number of months a woman was pregnant was positively associated with global cortical thickness (b = 0.002, p = 0.002). Cortical surface analysis revealed only positive regional associations with CT, including most regions of the DMN (Figure 1; Table 2), as well as several clusters outside the DMN. Notably, the anterior cingulate (ACG) did not show a significant association.

Conclusions

This work supports the hypothesis that pregnancy may be beneficial for late‐life brain health, particularly in regions important to AD‐pathology such as the DMN, with benefits extending beyond the effect of parity and breastfeeding. Future directions of this work include subcortical analysis and examining whether genetic risk for AD (such as APOE) modifies the relationship between pregnancy and cortical atrophy.
Marital Status and Gender among the Oldest Old: Implications for Cognitive Decline in the Life After 90 Study
Authors: Lee Elisa S , Whitmer Rachel A. , Gilsanz Paola , Meunier Claire C. , Lor Yi , Chen Nancy X , Corrada María M. M. , Posis Alexander Ivan B. , Mungas Dan M. , Decarli Charles , Kawas Claudia H. , George Kristen M.
Published: January 2025

Background

Widowhood is associated with cognitive impairment, which is salient for the oldest‐old, who are at high risk of cognitive decline and spousal loss. We assessed the association of marital status with cognitive decline in the LifeAfter90 Study (LA90) and examined effect modification by gender.

Method

LA90 enrolled participants aged 90+ who were long‐term members of Kaiser Permanente Northern California. Analyses included participants identifying as married, separated, or widowed (excluding single and never married individuals due to small numbers). At 6‐month intervals, the Spanish and English Neuropsychological Assessment Scale (SENAS) measured executive function (EF) and verbal episodic memory (VEM), standardized to baseline. Linear mixed models estimated the association of marital status with EF and VEM adjusting for baseline age, race/ethnicity, gender, education, depression, social and emotional support, interview mode and practice effects. Gender stratified models assessed differences between men and women.

Result

Participants (n = 943) had a mean age of 92.4±2.3, 61% were women, 61% were widowed, 29% were married, and 10% were separated. Women were more likely to be separated or widowed. Compared to widows, separated participants had higher average baseline EF (βEF (95% CI):0.14(‐0.07,0.35)) while married participants had lower (βEF: ‐0.13(‐0.29,0.03)), though these differences were not statistically significant. Over 1.8±1.35 years of follow‐up, married and separated participants had non‐significant faster decline in EF (Married pEF = 0.33; Separated pVEM = 0.55; Figure 1) and VEM (Married pEF = 0.34; Separated pVEM = 0.07; Figure 1) compared to widows. While associations were not significant in sex‐stratified models, married vs. widowed men had lower baseline EF (βEF:‐0.16(‐0.37,0.04)), separated vs. widowed men had better EF (βEF:0.29(‐0.19,0.76)), and separated vs. widowed women had better EF (βEF:0.12(‐0.13,0.36)). There were no significant differences in decline in sex‐stratified models, though slopes for separated men appeared slightly steeper (Figure 2).

Conclusion

In this diverse cohort of adults ages 90+, there were no significant differences in marital status and cognitive decline, though findings suggested separated participants may average better baseline cognition and steeper decline compared to widowed and married oldest old adults. Further research is necessary to assess the importance of marital status on cognitive aging and decline.
Animal protein intake is associated with frailty but not with cognition: an ELSI‐Brazil preliminary study of food consumption
Authors: Vasques Vivian Silveira , Borelli Wyllians Vendramini , Ferrari‐Souza João Pedro , de Freitas Núbia Alencar , Pauli Patricia , Suemoto Claudia Kimie , Zimmer Eduardo R.
Published: January 2025

Background

Diet is considered a complex modifiable risk factor for dementia and frailty. Some dietary patterns such as the MIND diet have been associated with a reduced risk of cognitive decline and dementia. Studies have shown mixed results with protein intake and frailty. However, the association of animal protein intake with cognitive performance and frailty is yet unclear. This study aimed to investigate the association of food group consumption with cognition and frailty in Brazilian older adults.

Method

This cross‐sectional study included baseline data from the Brazilian Longitudinal Study of Ageing (ELSI‐Brazil). The sample comprises cognitively unimpaired (CU, n = 4.155) and cognitively impaired (CI, n = 974) older adults (Table). Frailty was defined by weight loss, weakness, slow walking speed, exhaustion, and low physical activity. Cognition was calculated with a z‐score of orientation scores, animal fluency and memory recall. Individuals were defined as CI if the global cognition score was below 1SD of the sample mean. The association between food consumption and cognition was evaluated using a linear regression model corrected for age, sex, education, BMI, income, and frailty. A mediation model was developed with the association between cognition, frailty and animal protein intake (Figure).

Result

CI individuals showed increased rates of frailty (47.4% vs. 26.6%, p<0.001), and presented decreased weekly intake of fruits (8.9±6.2 vs. 9.6±6.3, p = 0.03) when compared with CU. Weekly intake of vegetables and animal protein was similar between groups (Table). Linear regression model identified total weekly intake of animal protein was associated with frailty, but not with cognition (Figure). Consuming animal protein in less than 5 days per week was associated with increased cognitive scores (β = 0.24±0.08, p<0.001), but this association was not significant when analyzing subgroups of animal protein (red meat, fish or chicken).

Conclusion

Our results suggest that weekly animal protein intake is associated with frailty but not cognition. However, intake of animal protein less than 5 days a week may have a neuroprotective effect. Further studies should understand the complex interaction of animal protein consumption in cognition and frailty.
Relationship Between Plasma P‐Tau‐217 And Amyloid PET In Racial And Ethnic Underrepresented Groups (RE‐URG) Compared With Non‐RE‐URG In LEARN And A4
Authors: Molina‐Henry Doris P. , Langford Oliver , Donohue Michael C. , Raman Rema , Yaari Roy , Sims John R. , Holdridge Karen Chilcott , Aisen Paul S. S. , Johnson Keith A , Rissman Robert A. , Sperling Reisa A ,   The A4 Study Team
Published: January 2025

Background

Individuals from diverse racial and ethnic groups are severely underrepresented in AD trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau (P‐tau217) as an early marker for brain Aβ pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. We examined the relationship between P‐tau217 and florbetapir PET standard uptake value ratios (SUVR) by self‐reported racial and ethnic groups in preclinical AD studies.

Methods

We examined the relationship between baseline florbeptair PET SUVR and plasma P‐tau217 levels (as determined by the electrochemiluminescence immunoassay), in cognitively unimpaired adults ages 65‐85 with elevated amyloid PET (A4 Study, placebo arm, N=522) and participants who did not display elevated amyloid but were otherwise eligible for the A4 Study (LEARN, N=471). Given the small numbers across each subpopulation, participants were grouped into racial and ethnic underrepresented groups (RE‐URG; N=100) and non‐RE‐URG (N=893), based on their self‐identified race and ethnicity. A linear regression model was fit to determine differences in the relationship between plasma P‐tau217 and florbetapir PET SUVR by RE‐URG status, adjusting for age, and APOE ϵ4 carrier status.

Results

Demographic characteristics of RE‐URG (N=100) and non‐URG (N=893) are displayed in the Table. Groups were balanced across, age, sex, and education, with a higher proportion of APOE ℇ4 carriers among non‐RE‐URG (38.8%) vs RE‐URG (24.0%). Mean plasma P‐tau217 levels were the same across groups (Table). Results from the linear regression model suggest that the relationship between P‐tau217 and florbetapir PET SUVR was similar across groups (p=0.22). Furthermore, APOE ℇ4 carrier status did not influence the relationship in either group (RE‐URG p=0.61; non‐RE‐URG p=0.09).

Conclusion

These findings suggest that there is no difference in the relationship between plasma P‐tau217 and elevated amyloid on florbetapir PET across racial and ethnic groups. Future analyses should corroborate these findings in a larger sample size, across different RE‐URG sub‐populations and examine whether plasma P‐tau217 reflects the differential amyloid prevalence previously reported for other biomarkers of amyloid.

Acknowledgment: Lilly Clinical Diagnostics Laboratory for the performance of P‐tau217 testing.
Association Between Baseline Plasma p‐tau181 Levels and Cognitive Trajectory in Healthy Geriatric Populations
Authors: Samalapa Rapas , Thanapornsangsuth Poosanu , Hemachudha Pasin , Luechaipanit Watayuth , Haethaisong Thanaporn , Chongsuksantikul Adipa , Boonyaprapatsara Gann , Chunharas Chaipat , Hemachudha Thiravat , Praditpornsilpa Kearkiat
Published: January 2025

Background

Dementia is a critical concern in the aging population, and understanding biomarkers associated with cognitive trajectories can provide valuable insights to improve diagnosis and intervention strategies.

Method

We conducted our study at a geriatric check‐up clinic at King Chulalongkorn Memorial Hospital, focusing on a healthy cohort of older adults aged 60 or older without dementia. This study included patients with available plasma p‐tau181 levels (Quanterix, Simoa) concurrent with cognitive evaluations no more than one year before the blood test, as well as at least one cognitive test administered after the blood test. The data collection period extended from March 2022 to January 2024. Cognitive evaluation was conducted using the Montreal Cognitive Assessment (MoCA), with the total score and subsection MoCA scores serving as outcome measures. The data were analyzed using linear mixed‐effects models, incorporating time from the blood test and plasma p‐tau181 level as fixed effects, with individual subjects considered as random effects.

Result

Among 52 healthy participants, the median age was 66.5 years (IQR: 65‐73), the median education was 16 years, and 80.8% were female. Baseline assessments showed a median MoCA score of 26 (IQR: 23‐27) (Table 1). The fixed‐effects model revealed a negative association between plasma p‐tau181 levels and MoCA total score (coefficient = ‐0.104) as well as memory subsection scores (coefficient = ‐0.101), although the findings were not statistically significant. In contrast, a significant positive association was observed between time and MoCA total score (coefficient = 0.003, p = 0.001) and memory subsection (coefficient = 0.002, p = 0.004) (Table 2).

Conclusion

The observed overall cognitive improvement over time in our study might imply a learning effect. Notably, among participants showing a positive correlation between time and cognitive performance, there is a trend towards lower cognitive function in those with elevated plasma p‐tau181. The lack of statistical significance in the association with plasma p‐tau181 may be attributed to small sample size and limited study duration. Our study suggests a potential association between plasma p‐tau181 and cognitive trajectories in a healthy geriatric population; however, future investigations with larger cohorts and extended follow‐up durations are necessary.
Exercise reduces white matter pathology in vascular cognitive impairment
Authors: Silva Narlon Cassio Boa Sorte , Dao Elizabeth , Falck Ryan S , Alkeridy Walid Ahmed , Tam Roger , Lam Kevin , Barha Cindy K , Crockett Rachel A , Brinke Lisanne F ten , Field Thalia S , Liu‐Ambrose Teresa
Published: January 2025

Background

Subcortical ischemic vascular cognitive impairment (SIVCI) is highly prevalent in older individuals. White matter hyperintensities (WMH) are a defining feature of SIVCI. There are sex differences in SIVCI, with females having higher volume and faster WMH progression than males. Resistance exercise training (RT) can slow WMH progression in cognitively unimpaired individuals; however, evidence in SIVCI is scarce. It is also unknown if biological sex influences WMH response to exercise. We investigated whether RT mitigated WMH in older individuals living with SIVCI and assessed whether biological sex moderated intervention effects.

Methods

This was a 12‐month single‐blind, randomized controlled trial. Participants were randomized to RT (n = 45, females = 32) or a balance and tone (BAT) control group (n = 46, females = 29). Study eligibility included: 1) age 55 years and older; 2) magnetic resonance imaging (MRI) evidence of cerebral small vessel disease; 3) mild cognitive impairment; and 4) absence of dementia. We measured WMH using a seed‐based pipeline incorporating T2‐ and PD‐weighted MRI scans. We extracted volumes for whole‐brain and lobe‐specific regions‐of‐interest. Differences between groups from baseline to 12 months were assessed via analysis of covariance adjusting for baseline WMH volume, estimated intracranial volume, and sex. We assessed sex‐specific effects via group‐by‐sex interaction terms.

Results

Seventy‐four participants (aged 74.3 [SD = 5.6], 65% females) completed follow‐up assessment and were included in the analysis. At 12 months, no main effect of intervention was observed for whole‐brain WMH volume (estimated mean difference [asinh‐transformed cm3]: ‐0.045, 95% CI: ‐0.124 to 0.034, p = 0.264). Biological sex significantly moderated intervention effects on whole‐brain WMH volume (p = 0.019), whereby RT reduced WMH volume (vs BAT controls) in females (‐0.113, 95% CI: ‐0.208 to ‐0.018, p = 0.021) but not males (0.081, 95% CI: ‐0.048 to 0.211, p = 0.216). Lobe‐specific analysis revealed that RT reduced WMH volume (vs BAT controls) in the parietal (‐0.074, 95% CI: ‐0.148 to ‐0.0004, p = 0.049) and temporal (‐0.069, 95%CI: ‐0.138 to ‐0.00003, p = 0.049) lobes. Group‐by‐sex interaction effects approached significance for parietal WMH volume (p = 0.052), suggesting an overall sex‐dependent effect of training.

Conclusion

RT may be an effective strategy to mitigate WMH progression in older individuals with SIVCI and females likely reap greater benefits than males.
Modifiable dementia risk factors in a memory outpatient clinic in Brazil
Authors: Lazzaretti Fernando Jacob , Felício Andressa de Oliveira , Patatt Julia , Aguzzoli Cristiano Schaffer , Schilling Lucas Porcello
Published: January 2025

Background

Low and middle income countries (LMIC) present a higher prevalence of dementia compared to high‐income countries due to health and social‐related modifiable risk factors inequities. Albeit the clear identification of these risk factors, the assessment and management of those situations before the development of dementia lacks attention in different health care levels. Thus, we aim to investigate the clinical impact and prevalence of health‐related risk factors among individuals referred to a specialized tertiary outpatient memory clinic from primary care facilities.

Method

We assessed 70 individuals (5 cognitively unimpaired (CU), 16 mild cognitive impairment (MCI), and 49 dementia) from an Brazilian Unified Public Health outpatient memory clinic from São Lucas Hospital located in the south of Brazil. The patients underwent clinical assessments comprising cognitive evaluation and a full neurologic examination. All participants underwent magnetic resonance imaging (MRI) and the clinical diagnosis was established by two experienced cognitive neurologists. We estimated the prevalence of risk factors for mild cognitive impairment (MCI) and dementia following those proposed by the Lancet Commission 2020. Tukey’s correction for multiple comparisons tested significant differences in risk factors among clinical groups.

Result

Mean age of the study population was 73 years (range, 31‐90 years); and 46% of whom were male. The most prevalent risk factors were depression (77.14%), hypertension (75.71%) and dyslipidemia (70%). Other notable factors included stroke (45.71%), diabetes (37.14%) and hearing loss (18.57%) (Figure 1). CU patients had significantly higher education attainment compared to MCI and dementia groups (Table 1). Stratifying the population according to appointment status revealed that patients who had their first appointment in 2023 exhibited a higher prevalence of depression (79%), hypertension (79%) and stroke (63%) (Table 2).

Conclusion

Our results highlight the high prevalence of dementia risk factors in patients referred by primary care units, but also in the outpatient memory clinic. Our findings provide a rationale for an urgent need of a better assessment and treatment of risk factors to reduce dementia incidence in LMIC.
Navigating Dementia Care in Northern Ontario: Exploring Health Professional Experience, Barriers and Facilitators
Authors: Shrestha Lucy , Shrestha Hom Lal
Published: January 2025

Background

Dementia is the seventh leading cause of death worldwide, impacting cognitive abilities and memory loss among aging populations. With the increasing prevalence of dementia, it is crucial to understand the distinct barriers and possibilities in providing care. Although there have been significant studies on dementia care, there is a lack of research that primarily focuses on the perspectives and worldviews of healthcare professionals, especially in the northern and rural regions of Ontario.

Objectives

The objective of this study is to identify the essential components required to support healthcare professionals in caring for people living with dementia (PLWD) in Northern Ontario.

Methods

Through an appreciative inquiry framework, data collection includes semi‐structured interviews with healthcare professionals caring for PLWD. A literature review was conducted to understand what has been published on the perspectives of health professionals in dementia care. A comprehensive search in Google Scholar, PubMed, and the National Library of Medicine was conducted through peer‐reviewed research articles published between 2014 and 2023 that focused on quantitative, qualitative, and mixed methods.

Result

The peer‐reviewed articles serve as a basis for comprehending dementia care focusing on the experiences and perceptions of healthcare professionals on dementia care within a Canadian context. These articles address several aspects, such as the challenges, barriers, facilitators, and recommendations for enhancing the quality of care provided to PLWD. Furthermore, they discussed the possibility of enhancing the accessibility of healthcare facilities, researching to gain a deeper understanding of providing higher‐quality care and emphasizing the importance of ongoing support and training for healthcare workers specializing in dementia care.

Discussion

The worldview of health professionals in dementia care aims to reform and enhance health professionals for PLWD to improve care, support, and inform future practice in this area. The findings are broadly shared and contribute to informing future policymaking by including specialized educational materials, training programs designed to raise awareness and practice, encourage advocacy, improve comfort levels, and ultimately enhance patient care for those with dementia. Furthermore, it could explore the possibility of implementing community‐driven initiatives and assistance programs for PLWD and their families residing in rural regions.
Impact of Knowledge About Alzheimer’s Disease on Interest in Participation in Biomarker Research
Authors: Etchison Taylor , Eliacin Johanne , Polsinelli Angelina J , Richards Ralph , Richards Mollie , Campbell Christopher , Shaw Pamella , Gao Sujuan , Van Heiden Sarah , Risacher Shannon L. , Hendrie Hugh C , Saykin Andrew J. , Wang Sophia
Published: January 2025

Background

Previous studies suggest limited knowledge about Alzheimer’s Disease (AD) is a barrier to underrepresented group participation in AD research. Connections between knowledge of AD and factors like social determinants of health or confidence in biomarker research have not been carefully examined. We hypothesized perceived knowledge about AD would be associated with research hesitancy independent of sociodemographics and trust of researchers.

Method

The AD‐REACH study surveyed 399 research‐naïve non‐Hispanic Black and white adults 55 years and older living in Indianapolis, Indiana. Participants reported perceived knowledge of AD on a 5‐point scale (5 = “I know what [AD] is, what causes it, and how to manage and prevent it;” 1 = “I know nothing at all”). Knowledge was dichotomized into higher (≥ 3) and lower (< 3) levels. Demographics were compared using chi‐squared tests and t‐tests. Ordinal logistic regression models examined the association between perceived knowledge about AD and outcome variables (e.g., hesitancy towards research participation) and were adjusted for sociodemographics and very high trust of researchers.

Result

Those who reported being Black, male, from a higher Area Deprivation Index, or having less than 16 years of education had lower perceived knowledge about AD (Table 1). Trust of researchers was not associated with perceived knowledge. Those reporting lower AD knowledge described more hesitancy to participate in biomarker research (53.0% vs 72.7%, OR 2.50, 95% CI 4.35‐1.39, p = 0.002) and blood draw (62.3% vs 80.9%, OR 2.17, 95% CI 4.00‐1.19, p = 0.012) but not neuroimaging procedures (Table 2). Those with lower perceived knowledge of AD were more likely to need additional information to make decision about whether to participate in research (58.1% vs 29.9%, OR 3.70, 95% CI 9.09‐1.49, p = 0.005) (Table 3).

Conclusion

Populations with health disparities report lower knowledge of AD, and lower perceived knowledge is associated with research hesitancy, especially for biomarker procedures. Perceived AD knowledge is also independent from trust, suggesting the feasibility of a two‐pronged intervention to foster diverse participation in AD biomarker research. Future studies will need to confirm these findings in other cohorts and examine how culturally tailored strategies to increase AD knowledge may reduce research hesitancy among underrepresented groups.
Sex Specific Associations of BMI and Brain Regional Tau Deposition in a community‐dwelling cognitively normal older adult sample
Authors: Dominguez Joanna , Cesar Oliver , Gills Joshua L , Sogade Anamarie , Browne Laurel Y , Weisgerber Elizabeth , McBride Julian , Valkanova Elena , Mbah Alfred , Figueredo Luisa F , Jean‐Louis Girardin A , Masurkar Arjun V. , Osorio Ricardo S. , Bubu Omonigho Michael
Published: January 2025

Background

Increased body mass index (BMI) in mid‐life is associated with a higher risk of Alzheimer’s disease (AD). Neurofibrillary tangles (NFTs), comprised of hyperphosphorylated aggregated tau protein, are the pathological hallmark of neurodegenerative tauopathies including Alzheimer’s Disease (AD). The relationship between sex‐dependent adiposity in late adulthood and tau NFT pathology remain inconclusive. We examined sex differences between BMI and tau‐PET pathology among cognitively normal individuals.

Method

This cross‐sectional analysis consisted of 104 community‐dwelling cognitively normal older adults (mean±SD; males (n = 42): age = 72.8±6.5y; females (n = 62): age = 72.6±6.8y) from ongoing NYU longitudinal studies on memory and aging. Subjects completed clinical assessments and two PET scans (FBB and 18F‐ PI2620). Standard uptake value ratio (SUVR) values from images were computed using FreeSurfer, and normalizing to cerebellar grey matter. For tau, data were analyzed from composite regions corresponding to Braak pathological stages I–VI, (Braak I: entorhinal cortex; Braak II: hippocampus; Braak III: parahippocampal gyrus, amygdala, fusiform gyrus, lingual gyrus; Braak IV: neocortical regions including the insular cortex, medial temporal gyrus; Braak V: superior temporal gyrus; Braak VI: occipital neocortex), and control brain regions not expected to contain NFTs including the pericalcarine cortex, corpus callosum, and caudate nucleus. Linear mixed effects regression models examined association between BMI, sex, BMI*sex, PET SUVR amyloid & tau. Models were adjusted for age, race, amyloid and ApoE status.

Result

Relative to females, males were on average slightly more educated (males, females; 17.0±2.4y, 16.6±2.1y), had similar BMI (29.6±10.3 kg/m2, 29.5±10.8 kg/m2), and had higher blood pressure (Systolic/diastolic; 168.4/116.3 mmHg, 156.9/100.7 mmHg). Sex and BMI were each associated with SUVR tau and the BMI*sex interaction was significant (p<0.05 for all). Males with higher BMI, showed increased SUVR tau burden (β[IV] = β[SE}; β[BMI*sex] = 0.0054[0.0025], p = 0.031), corresponding to Braak stage I (β[BMI*sex] = 0.0122[0.0055], p = 0.032), Braak stage III (β[BMI*sex] = 0.0054[0.0025], p = 0.034), Braak stage IV (β[BMI*sex] = 0.0058[0.0020], p = 0.006), Braak stage V (β[BMI*sex] = 0.0048[0.0019], p = 0.014), and Braak stage VI (β[BMI*sex] = 0.0039[0.0017], p = 0.026).

Conclusion

In this sample of community‐dwelling cognitively normal older adults, higher BMI in males was associated with increased tau NFT burden. Thus, excessive adiposity in late‐life may contribute to Alzheimer’s disease pathology for males.
Dementia Risk Factors Are Undiagnosed and/or Uncontrolled in a Latino and Black Aging Cohort
Authors: Lachner Christian , Piura Yoav D , Aduen Paula , Carrasquillo Minerva M. , White Richard O , Graff‐Radford Neill R. , Day Gregory S
Published: January 2025

Background

The prevalence of dementia in populations that are underrepresented in research is projected to increase with population aging. Latino and Black individuals, the largest underrepresented populations in the US, experience a higher dementia burden than non‐Hispanic White individuals, which is not explained by ethnoracial biological factors. Disparities in structural and social determinants of health may contribute to the preponderance of medical conditions known to increase dementia risk, including potentially modifiable factors in Latino and Black communities. To assess the scope of this problem, we measured the frequency of common modifiable dementia risk factors in community‐dwelling, cognitively normal, Latino and Black adults.

Method

Cognitively normal community‐dwelling Latino and Black adults, ≥45‐years‐old, were enrolled within our longitudinal study of memory and aging at Mayo Clinic in Florida (Jacksonville, FL) and completed a baseline assessment between 3/2022 and 10/2023. Demographics, and self‐reported race/ethnicity and history of dementia risk factors were recorded. Dementia risk factors were objectively sampled through clinical interview (depression: Geriatric Depression Scale ≥5), examination (hypertension: BP >130/80 mmHg; obesity: BMI≥30), and serum analyses (hyperlipidemia: total cholesterol<200mg/dL, HDL>50mg/dL, LDL<100mg/dL, Triglycerides<150mg/dL; diabetes: HbA1C >5.6%, vitamin B12 deficiency: <350 ng/dL).

Result

86 participants (43 Latino, 43 Black), 65.8 (8.8) years‐old, female (62.8%), with 16 (2.4) years of education were assessed. Dementia risk factors were frequent in Latino and Black participants, including hypertension (63%, 90%; p = 0.005), hyperlipidemia (93%, 89%; p = 0.702), obesity (33%, 44%; p = 0.370), diabetes (60%, 47%; p = 0.370), vitamin B12 deficiency (21%, 21%; p = 0.989), and depression (5%, 24%; p = 0.781). These risk factors were unrecognized or suboptimally managed in a substantial proportion of Latino and Black participants: hypertension (56%, 73%; p = 0.170), hyperlipidemia (80%, 73%; p = 0.591), diabetes (57%, 47%; p = 0.502), vitamin B12 deficiency (21%, 21%; p = 0.789), and depression (5%, 3%; p>0.99).

Conclusion

Potentially modifiable dementia risk factors were detected in the majority of community‐dwelling Latino and Black cognitively normal older‐adults and were frequently unrecognized or suboptimally managed. Proactive screening for known dementia risk factors may provide opportunities for targeted interventions to improve brain health and decrease dementia disparities in underrepresented populations.
Multicentre validation of the dementia with Lewy bodies‐related metabolic brain pattern
Authors: Perovnik Matej , Simončič Urban , Kos Hana , Jamšek Jan , Kramberger Milica G , Brendel Matthias , Camacho Valle , Vandenberghe Rik , Garibotto Valentina , Ochoa‐Figueroa Miguel A , Padovani Alessandro , Morbelli Silvia , Ferreira Daniel , Trošt Maja ,   Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

Background

Dementia with Lewy bodies (DLB) is a an α‐synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB‐related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis. DLBRP has been identified in few different cohorts but lacks a multicentric validation.

Methods

FDG PET scans from 259 DLB patients and 176 normal controls (NC) were obtained from eight centres from European DLB Consortium (EDLB, 180 patients), Alzheimer’s disease Neuroimaging Initiative (ADNI, 135 NC) and local dataset from Ljubljana (LJU, 79 patients and 41 NC). FDG PET scans were pre‐processed and we used topographic profile rating to calculate the DLBRP expression (i.e. subject scores). Subject scores were compared between groups using t tests and ANOVA and correlated with clinical parameters using Pearson’s correlation coefficient.

Results

Patients from different centres differed in MMSE (p < 0.001), proportion of patients with parkinsonism (p < 0.001) and visual hallucinations (p < 0.001), but not in age (p = 0.15) or sex distribution (p = 0.13). DLB patients from all centres had significantly higher DLBRP expression than NCs (all p < 0.001). We could accurately distinguish between DLB and NC (AUC = 0.983) based on DLBRP expression. We observed a negative correlation between DLBRP expression and MMSE (r = –0.30, p < 0.001). The expression of DLBRP differed among centres, post hoc analysis showed that only patients from Barcelona had significantly lower DLBRP subject scores in comparison to other groups but they were also less cognitively impaired. Patients with visual hallucinations (p < 0.001) had significantly higher DLBRP expression than those without hallucinations and patients with abnormal Datscan™ (p = 0.02) had higher DLBRP expression than those with normal Datscan™. Other core features, levodopa or antidementives did not affect the DLBRP expression.

Conclusions

We showed that DLBRP can accurately distinguish between DLB and NC from multiple centres and different scanners. The DLBRP expression correlated with measurements of cognitive impairment. This validation study confirms that the DLBRP is a robust metabolic imaging biomarker of DLB.
Empowering Communities: Culturally Competent Dementia Awareness Education for Older Adults in Miami‐Dade County
Authors: Madan Krisstina , Brown Ellen L , Gordon Vanessa
Published: January 2025

Background

The purpose of this Doctor of Nursing Practice Project (DNP) was to explore community stakeholders' perspectives on a newly developed Dementia Awareness Educational Video (DAEV) within a culturally diverse community. Dementia is a global public health concern, with far‐reaching implications affecting millions of individuals, families, and communities. Raising awareness and delivering effective education is paramount, especially within culturally diverse communities.

Method

This qualitative study explored the potential effectiveness of the DAEV. A virtual focus group was conducted. Half (n = 3) of the participants were White and 2 (33%) were Black or African America (one participant was identified as “other”). Most participants were of Hispanic descent (n = 4, 66%). All of participants were highly educated including 2 (33%) participants having a Doctoral degree, 3 (50%) master’s degrees, and 1 (16.7%) bachelor’s degree. A semi‐structured format allowed for exploration of participant perspective on the clarity of the message in the DAEV, overall reaction, and recommendations for community dissemination.

Result

Two main areas of improvement were identified: enhancing message clarity and areas to disseminate the video. To enhance the clarity of the message suggestions included incorporating more images, addressing language accessibility, and ensuring that each video concludes with a clear and concise call to action. Regarding dissemination of the DAEV physician offices, waiting rooms, online platforms, social media and community partners and stakeholder websites were all suggestions.

Conclusion

In the future, these findings will inform the enhancement of the DAEV, ensuring it serves as an effective tool for raising dementia awareness within culturally diverse communities. The collaborative effort among stakeholders, guided by the insights gathered from this focus group, reinforces the commitment to fostering a more dementia‐informed society, where diverse communities receive the support and information, they need to face this critical healthcare issue.