bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial and ethnic differences in lifetime Medicare expenditures for dementia patients
Authors: Olchanski Natalia , Zhu Yingying , Liang Lichen , Cohen Joshua T , Neumann Peter J , Faul Jessica D , Fillit Howard M , Freund Karen M , Lin Pei‐Jung
Published: December 2023

Background

Research on racial and ethnic disparities in lifetime dementia costs is sparse. We analyzed lifetime Medicare expenditures for dementia patients to identify when during the course of care costs are the highest, and whether these costs differ by race and ethnicity.

Method

We analyzed data from the 2000‐2016 Health and Retirement Survey (HRS) linked with corresponding Medicare claims to estimate total Medicare expenditures for four “phases”: 1) the year before dementia diagnosis; 2) the first year following a dementia diagnosis; 3) ongoing care for dementia after the first year; and 4) the last year of life. We then estimated each patient’s phase‐specific and lifetime Medicare expenditures by using a race‐specific survival model and monthly expenditures adjusted for demographics, socio‐economic status, year of dementia diagnosis, nursing home status, functional limitations, cognitive impairment, comorbidities, and Medicaid eligibility status.

Result

Adjusted mean lifetime Medicare expenditures for non‐Hispanic Blacks ($166,548) and Hispanics with dementia ($163,425) exceeded corresponding expenditures for non‐Hispanic whites ($135,648) (Figure). In the year preceding and immediately following an initial dementia diagnosis, mean Medicare expenditures for non‐Hispanic Blacks ($26,384 and $20,824) exceeded expenditures for Hispanics and non‐Hispanic whites (ranging $21,340‐23,379 and 17,382‐18,085). Ongoing care costs for non‐Hispanic Blacks with dementia (mean $1,734/month) exceeded costs for Hispanics ($1,538/month) and non‐Hispanic whites ($1,424/month). Of the four phases, the last year of life was responsible for the greatest cost contribution: $52,003 for non‐Hispanic Blacks, $48,377 for Hispanics, and $39,648 for non‐Hispanic whites.

Conclusions

Total mean Medicare expenditures for non‐Hispanic Black and Hispanic beneficiaries with dementia exceeded corresponding expenditures for non‐Hispanic whites. Expenditures were highest for non‐Hispanic Blacks with dementia in every phase of care. Compared to non‐Hispanic whites, Hispanics had lower expenditures in the first year following dementia diagnosis and similar monthly ongoing care expenditures but much higher expenditures during their last year of life. Research should identify factors contributing to the disparities identified here so that policy makers can address problems adversely affecting disadvantaged populations.

Figure: Estimated mean lifetime Medicare expenditures for beneficiaries newly diagnosed with dementia, by phase of care and by race and ethnicity (adjusted)
Preserved Autophagy in Cognitive Intact Non‐Demented Individuals with Alzheimer’s Neuropathology
Authors: Fracassi Anna , Tumurbaatar Batbayar , Scaduto Pietro , Guptarak Jutatip , Jupiter Daniel , Taglialatela Giulio
Published: December 2023

Background

Alzheimer’s disease (AD) is a terminal neurodegenerative disease and the most common cause of dementia. Notably, some individuals, here referred to as Non‐Demented individuals with Alzheimer’s Neuropathology (NDAN) are cognitively intact despite the presence of neuropathology consistent with fully symptomatic AD and have decreased Tau oligomers at synapses. Growing evidence supports that dysfunctional autophagy, the primary cell mechanism responsible for removing protein aggregates and a route of clearance for Tau in healthy neurons, is a major finding in demented AD patients. However, the association of autophagy with maintenance of cognitive integrity in resilient individuals has not been evaluated. Thus, the understanding of the neuroprotective mechanisms to evade cognitive decline to preserve synaptic functional integrity is important for the development of therapeutic approaches to prevent dementia.

Method

Here we evaluated autophagy as a key protective mechanism for maintenance of cognitive integrity in NDAN subjects by efficient removal of tau oligomers. Using postmortem hippocampal samples from age‐matched healthy controls (n = 6), AD (n = 7) and NDAN (n = 7) we performed immunofluorescence and comparative western blot analyses for regulatory molecules and ATGs (autophagy‐related genes) involved in autophagy. Tauopathy was accessed by the expression and phosphorylation levels at Ser202/Thr205 (AT8), Thr231 (AT180) and Ser396 (PHF13.6) of Tau oligomers.

Result

We found that NDAN subjects have significantly increased regulatory Beclin‐1, and Atg16L, Atg12, Atg3, Atg5, Atg7, LC3AB, and proteasomal PSMA5 but not lysosomal LAMP1 as compared to AD. Expression levels were comparable with healthy controls. Autophagic proteins, except p62, were negatively correlated to Tau oligomer (>65 kDa), but not to total Tau (>45 kDa), indicating autophagy being specific to tau oligomer clearance. Tau oligomer expression and levels of phosphorylation at Ser202/Thr205, Thr231, and Ser396 were significantly reduced in hippocampal tissue in NDAN as compared to AD, also confirmed by immunofluorescence analyses of Tau tangles.

Conclusion

Our results indicate, for the first time, intact autophagy and associated reduced tauopathy as one of protective mechanism in cognitive intact NDAN. This novel observation supports the potential of autophagy‐induced strategies in AD therapeutics
Evaluation of quantitative measurements of tau pathology with semi‐quantitative ratings and age
Authors: Denning Amanda E , Ittyerah Ranjit , Sadeghpour Niyousha , Chung Eunice , Ravikumar Sadhana , Sadaghiani Shokufeh , Capp Noah , Teunissen‐Bermeo Eric , Arezoumandan Sanaz , Ohm Daniel T , Schuck Theresa , Robinson John L. , Grossman Murray , Lee Eddie B , Trojanowski John Q , Wisse Laura EM , Das Sandhitsu R. , Wolk David A. , Irwin David J. , Yushkevich Paul A.
Published: December 2023

Background

It is assumed quantitative digital neuropathology methods will provide more information than semi‐quantitative ratings, but this presumption lacks formal assessment. Here, we compare quantitative, whole‐slide measurements of phosphorylated tau tangles and threads with semi‐quantitative tau pathology ratings. We evaluate whether quantitative measurements provide additional prediction beyond Braak stage for variables associated with tau pathology, examining the association of quantitative tau measurements in high Braak stages with age at death and measures of severity of TDP‐43 and alpha‐synuclein co‐pathologies. We hypothesized that even within the same high Braak stage, quantitative tau measurements would decrease with age at death, as younger patients often require more tau pathology for disease severity comparable to older patients, and increase with higher co‐pathology ratings, since prior work suggests co‐pathologies increase with disease severity.

Method

We scanned 6µm tissue sections stained with phosphorylated tau PHF1 in 14 brain regions from 215 patients with Alzheimer’s Disease continuum neuropathological diagnoses (53% male, age = 74.37 ± 11.51). A machine learning method (Figure 1) generated summary measures of tangle and thread pathology for each slide (Yushkevich et al., 2021, Sadaghiani et al., 2022). Semi‐quantitative tau ratings (0‐3) were also available in nine regions and compared to quantitative measurements in matching regions. In 150 patients with high Braak stages (V/VI), correlation analyses were performed using summary scores averaging semi‐quantitative ratings of TDP‐43 in medial temporal lobe regions (“TDP‐43 severity”), and alpha‐synuclein in commonly affected regions (“alpha‐synuclein severity”).

Result

Figure 2 shows high overall agreement between quantitative tau measures and corresponding semi‐quantitative ratings. When evaluating quantitative tau measurements in high Braak stage patients, after Bonferroni correction we found significant negative associations between age and tangles in middle frontal cortex, orbital frontal cortex (OFC), and thalamus, and between age and threads in OFC. We found significant positive association between TDP‐43 severity and tangles in substantia nigra, but no associations with alpha‐synuclein severity (Figure 3).

Conclusion

Quantitative tau measurements largely agree with established semi‐quantitative ratings. Significant associations of quantitative tau measurements with TDP43 pathology and age were found within high Braak stage patients, suggesting quantitative pathology measurements can offer additional information beyond stage alone in these patients.
Autonomic Function and Cognitive Function in the U.S. POINTER Neurovascular Ancillary Study
Authors: Shaltout Hossam A , Garcia Katelyn R , Leng Xiaoyan , Baker Laura D , Snyder Heather M , Bailey Margie J , Brinkley Tina E
Published: December 2023

Background

Autonomic regulation plays a major role in maintaining stable blood supply to the brain. Impaired autonomic function, as evidenced by high blood pressure variability (BPV) and/or low heart rate variability (HRV), is common in older adults and is associated with reduced perfusion, which can ultimately lead to impaired cognitive function. The U.S. POINTER Neurovascular (POINTER‐NV) ancillary study is an ongoing study designed to evaluate autonomic function in participants from the U.S. POINTER trial. Here we describe the baseline characteristics of the POINTER‐NV participants, focusing on autonomic measures and their relationship to cognitive function.

Method

Continuous blood pressure and ECG recordings were used to assess BPV, HRV, and sympathovagal balance. Autonomic variables were compared according to cognitive status using the baseline Clinical Dementia Rating Scale Sum of Boxes (CDR‐SB) score. Linear regression was used to assess cross‐sectional associations between sympathovagal balance and BPV variables and composite scores for global cognition, executive function, memory, and processing speed, with and without adjustment for age, sex, and race/ethnicity.

Result

Autonomic measures were available for 212 POINTER‐NV participants (mean age: 67.9 ± 5.4 years, 67% female, 33% people of color). There were no significant differences in BPV or HRV measures between participants with normal cognition (CDR‐SB score = 0) and those with possible cognitive impairment (CDR‐SB score = 0.5–1.0). Higher sympathovagal balance was significantly associated with higher scores of global cognition, executive function, and processing speed; however, this association became statistically insignificant after adjustment for age, sex, and race/ethnicity. Higher BPV measured as standard deviation of mean arterial pressure (SDMAP) was associated with lower scores for episodic memory after adjustment for age, sex, and race/ethnicity (p = 0.03). There was some suggestion that lower HRV might be associated with worse cognition, however, these associations were inconsistent across cognitive domains and did not remain after covariate adjustment.

Conclusion

Age‐related changes in autonomic function can promote cognitive decline and dementia. Our data are consistent with prior evidence suggesting a role for sympathovagal balance and blood pressure variability in modulating cognitive function
Overexpression of astrocytic glutamate transporters alleviates hyperexcitability in mouse model of Alzheimer’s Disease
Authors: Gollihue Jenna L , Gant Christopher C , Kraner Susan D. , Norris Christopher M.
Published: December 2023

Background

Astrocytes are the main cells responsible for clearing glutamate from the synapse; their glutamate transporters quickly and efficiently clear glutamate within the synaptic cleft, preventing neuronal excitotoxicity. In mouse models and human cases of Alzheimer’s Disease (AD), the astrocyte‐specific glutamate transporter (Glt1 in rodents and EAAT2 in humans) is decreased. Our goal is to study the effects of decreased glutamate transporters on synaptic measures of function and plasticity.

Method

Using a 5XFAD mouse model of amyloid pathology, we utilized an adeno‐associated virus (AAV) to over‐express Glt1 in the hippocampus. Electrophysiological field recordings examined the role of astrocyte‐specific glutamate transporters in synaptic plasticity and hyperexcitability. Animals received injections of AAV‐Luciferase (control) in one hippocampus, and AAV‐Glt1a in the contralateral hippocampus. Field recordings were performed to assess excitatory postsynaptic potentials in the hippocampal CA1 stratum radiatum elicited by stimulation of CA3 axons.

Result

Compared to control (AAV‐Luciferase), AAV‐Glt1 significantly increased the expression of glutamate transporters in hippocampal tissue. We then compared measures of neuronal hyperexcitability, synaptic strength, and long‐term synaptic potentiation. Results indicate that there is more hyperexcitability in control tissues compared to AAV‐Glt injections, as evident by decreased population spike thresholds.

Conclusion

Others have reported hippocampal hyperexcitability may lead to memory impairment; in human cases of AD it is thought to encourage epileptic episodes. By using our AAV‐directed technique to increase glutamate transporters, and thus reduce network hyperexcitability, we will be able to examine how reactive astrocytes and their loss of glutamate transporters contribute to memory or cognition loss. Ongoing studies will do exactly this‐ use a mouse model of AD with and without AAV Glt1 overexpression to determine changes in behavioral cognitive outcome measures that may be attributed to hyperexcitability in neuronal networks.
The Puipui Malu Manatu study to assess Alzheimer’s Disease and Related Dementias (ADRD) prevalence in American Samoa
Authors: Tofaeono Vaatausili , Galvin James E , Park Van Ta , Pagano Ian , McCutchan Jueta , Thompson Lemala , Atuatasi Casuallen , Faaiuaso Siumukuka , Vaofanua Tulimalefoi
Published: December 2023

Background

American Samoa is the only U.S. territory located south of the equator. The U.S. Census recorded 46,466 residents, with 11,025 (23.8%) of the population age 50 and over. Healthcare access is extremely limited and the lack of culturally‐sensitive screening tests characterizing the earliest signs of impairment, correspondence to Alzheimer’s Disease and Related Dementias (ADRD) biomarkers, and potential benefits versus harms from screening are barriers for the detection of ADRD. The inability to detect mild cognitive impairment (MCI) and ADRD may affect eligibility determination for acre and services, impeded case ascertainment, and limit ADRD research. Furthermore, social determinants of health, genetic risks, and lifestyle factors may plan an important role in relative vulnerability or resilience of the American Samoa population to develop MCI and ADRD.

Method

Using our prior work, partnerships, and nascent research infrastructure, we submitted a R01 application creating the Puipui Malu Manatu, or Protecting Memories, study to conduct important phenotypic and genotypic characterization of ADRD in a probability sample of 981 Samoans age 50 and above. Our hypotheses are: 1) ADRD knowledge and research readiness is low, 2) culturally‐adapted instructions will detect MCI and ADRD; and 3) unique patterns of plasma and genetic biomarkers define ADRD in American Samoa older adults.

Result

We were funded by the National Institutes of Aging (RF1AG075904) for the project to complete the following specific aims: 1) Test ADRD knowledge, health literacy, research readiness and determine ADRD resilience and vulnerability factors, and cognitive status using culturally adapted instruments, 2) Conduct Gold Standard evaluations using the Uniform Data Set (UDSv3.0) from the NIA Alzheimer’s disease research Center program to determine a population‐based prevalence of MCI and ADRD for harmonization, data sharing, and comparison to other groups, 3) Cross‐validate Gold Standard dementia evaluations with genetic and plasma Amyloid‐Tau‐Neuronal Injury/Neurodegeneration framework biomarkers in our probability sample and compare to information available for other racial/ethnic groups.

Conclusion

Strong collaborations are needed to conduct novel ADRD research studies in American Samoa that is resource poor, yet culturally rich. Our approach allows to weave Westernized and Indigenous approaches to increase knowledge in this field for our population.
Blood‐brain barrier permeability and risk of conversion to dementia in patients with mild cognitive impairment
Authors: Puig‐Pijoan Albert , Fernández‐Lebrero Aida , Garcia‐Escobar Greta , Navalpotro‐Gómez Irene , Manero‐Borr Rosa Maria , Contador José , Suárez‐Pérez Antoni , Puente‐Periz Víctor , Grau‐Rivera Oriol , Suarez‐Calvet Marc , Jimenez‐Balado Joan , Roquer Jaume , Ois Angel ,   CardioStressCI Consortium. ERA‐CVD Transnational Call
Published: December 2023

Background

Cardiovascular risk factors (CVRF) have been associated with an increased risk of cognitive decline and dementia. Increase of blood‐brain barrier permeability (BBBp) measured by CSF/serum albumin ratio (Qalb) have been associated with CVRF. The aim of this study was to analyze the possible role of Qalb as a predictor of conversion to dementia in patients with mild cognitive impairment (MCI).

Method

A total of 144 individuals with MCI were recruited from the BIODEGMAR cohort at Hospital del Mar (Barcelona) from 2017 to 2021. Study protocol included neuropsychological assessment, blood sampling, lumbar puncture and brain MRI. Follow‐up visits were performed yearly (12 +‐2 months) until January 2023. The endpoint of the study was a diagnosis of dementia (Global Deterioration Scale –GDS‐ > 3 and/or Clinical Dementia Rating ‐CDR‐ score > 0.5). BBBp was measured by CSF/serum albumin ratio (Qalb). Azheimer’s Disease (AD) was biologically‐defined according to CSF Aβ42/p‐tau ratio (AD+/‐). A composite vascular score (CVS) was calculated by assigning one point for the presence of each of the following CVRF (hypertension, hyperlipidemia and diabetes mellitus) plus another point if Fazekas scale higher than 1 or presence of brain infarcts on MRI. We performed a multivariate Cox regression analysis including the following variables: age, sex, AD and CVS.

Result

Sixty‐two cases (39.2%) developed dementia in a median follow‐up of 25.89 +/‐ 13.98 months. Univariate analysis showed that Qalb (p < 0.01), AD+ (p < 0.01) and CVS (p = 0.016) were associated with dementia. The regression model results showed an independent relationship between conversion to dementia and Qalb, HR = 1.333 (95% CI 1.185‐1.499) and AD+, HR = 4.118 (2.202‐7.699).

Conclusion

An increase in BBBp was independently associated with a higher risk of conversion to dementia in MCI patients. This result points to a potential role of Qalb as a useful biomarker of clinical prognosis of MCI patients.
Walking energetics and white matter hyperintensities: findings from the Baltimore Longitudinal Study of Aging (BLSA)
Authors: Dougherty Ryan J. , An Yang , Tian Qu , Wanigatunga Amal A , Simonsick Eleanor M , Ferrucci Luigi , Resnick Susan M. , Schrack Jennifer A
Published: December 2023

Background

White matter hyperintensities (WMH) increase with advancing age and may contribute to the development of Alzheimer’s Disease. Energy utilization, as defined by walking efficiency, worsens with advancing age and is a prognostic marker of physical and cognitive function in older adults. While both WMH and energy utilization have been associated with cognition and Alzheimer’s‐related pathology, the links between WMH and walking energy utilization are unexplored. The purpose of this study was to examine the cross‐sectional association between walking energy utilization and WMH in cognitively normal middle‐to‐late aged men and women.

Method

The study included 708 BLSA participants who completed standardized slow‐ and peak‐pace walking assessments with indirect calorimetry (VO2 ml/kg/min) and underwent brain magnetic resonance imaging. Energy utilization was defined as the ratio of slow‐to‐peak walking energy capacity (the cost‐ratio), which describes the percentage of peak walking capacity required for the standardized slow walking task; a higher percentage indicates worse energy utilization. T2‐weighted scans and FLAIR images based on a validated support vector machine classifier approach were used to quantify total WMH volumes, which were log‐transformed to normalize the distribution. Sample characteristics were summarized using means and standard deviations. Linear regression was used to examine the association between WMH and the cost‐ratio adjusted for total white matter volume, age, sex, race, lean mass, fat mass, education, height, and comorbid conditions.

Result

In this sample of cognitively normal adults (56% women, mean age 66.7±15.3 years) the average cost‐ratio was 71.6±12.2% (range 34.3‐98.7) and mean log10(WHH) was 3.01±0.80 (range 0.08‐4.68). After covariate adjustment, a higher cost‐ratio was associated with greater total WMH (B = 0.008; SE = 0.002; p<.001; Table 1). Aside from age and total white matter volume, which track closely with WMH, the cost‐ratio was most strongly associated with WMH in our model (Table 1).

Conclusion

In a large sample of community‐dwelling middle‐to‐late aged adults, walking energy utilization was associated with WMH volumes, suggesting that a combination of higher energy cost of walking and lower peak walking energy capacity is associated with adverse brain health in mid‐to‐late life. Longitudinal research is needed to elucidate the directionality and temporality of the observed association.
Apathy, empathy and depression in Alzheimer’s disease and frontotemporal dementia: Examining the constructs and white matter correlates
Authors: Quang Halle , Mencevski Filip , Piguet Olivier , Husain Masud , Landin‐Romero Ramon , Kumfor Fiona
Published: December 2023

Background

Apathy and reduced empathy are commonly observed in Alzheimer’s disease (AD) and the core features of behavioural‐variant frontotemporal dementia (bvFTD). Depression is also prevalent in these syndromes. Recent work has proposed a multidimensional framework of apathy which includes three aspects of apathy: executive apathy (reduction of planning and organisation), emotional apathy (emotional indifference and decreased social engagement) and initiation apathy (reduced behaviour execution). These aspects can manifest as symptoms resembling empathy loss and/or depression. The extent to which these symptoms represent similar/divergent clinical dimensions, and their underpinning neural networks, remains unclear. This study investigated the interrelations between apathy, empathy loss and depression, and its white matter correlates, in AD and bvFTD.

Method

Thirty‐four AD and 51 bvFTD patients participated in the study. Items of the Dimensional Apathy Scale, Interpersonal Reactivity Index and Depression Anxiety Stress‐Depression Subscale were examined using Principal Component Analysis (PCA). White matter integrity and its associations with clinical components were measured via changes in fibre density and cross‐section using fixel‐based analysis.

Result

Three components were identified through the PCA (Fig 1). Component 1 consisted of items assessing emotional apathy and empathy, while Component 2 included executive apathy items. Finally, all depression items loaded into Component 3. Regarding white matter correlates, Component 2 were strongly related to reduced white matter bundle density and cross‐section in fibres connecting the bilateral frontal lobe and subcortical structures (Fig 2), whereas Components 1 and 3 were associated with distributed white matter reductions.

Conclusion

This study demonstrates that while emotional apathy and empathy loss share the underlying construct, executive apathy and depression are rather independent. White matter changes have strong implications for executive apathy, but not for emotional apathy, empathy and depression. Improved conceptualisation of these symptoms will be important for the development of personalised symptom‐specific therapies.
Using Spontaneous Speech Recognition as a Biomarker to Distinguish Dementia Patients
Authors: Nyongesa Cynthia , Pa Judy
Published: December 2023

Background

Digital biomarkers such as individual speech recordings, are a cost‐effective tool for assessing cognitive status using linguistic and acoustic content. The purpose of this study is to investigate whether Natural Language Processing (NLP) methods and audio feature extraction can distinguish spontaneous speech outputs in dementia patients from a healthy population.

Method

240 audio samples and transcripts of clinician‐participant dialogues involving the Cookie‐Theft visual description were acquired from the DementiaBank Pitt corpus (Dementia group (DG) n = 169; healthy controls (CG) n = 71). Lexical variety, syntactic complexity, salience of information, disfluency patterns, and sentiment analysis were evaluated. Sound synthesis and an acoustic R analysis package were used to filter and examine acoustic properties of recorded audio such as silence and speech segmentation, pitch tracking, and frequency modulation of vibrato or jitter. DG and CG were compared using non‐parametric Kruskal‐Wallis tests, Dunn’s multiple comparison, and Mann‐Whitney U‐test in the statistical analysis. In comparison to CG, we hypothesized that DG would differ in levels of lexical diversity, grammatical complexity, and overall salience.

Result

Overall, text analysis showed no variations in disfluencies between groups, but there were significant differences in lexical diversity, syntactic complexity and reference rate to reality (p<0.0001). Additionally, there were no appreciable differences in the frequency of salient information between the two groups, however the frequency of non‐salient information and disfluencies was considerably higher in the DG (p<0.05). Analysis of acoustic features revealed that DG had longer average speech duration and speech segment durations compared to CG (p<0.001).. On the other hand, the rate of change of acoustic characteristics including pitch, mean entropy, and harmonics‐to‐noise ratios did not significantly differ between DG and CG.

Conclusion

In conclusion, this paradigm reveals that, in comparison to healthy controls, dementia patients exhibited increased lexical diversity yet lower linguistic complexity, and a shift towards characterizing non‐salient objects in given stimuli, as well as longer segments of speech. Further examination of the rhythmic and acoustic characteristics of speech may provide a comprehensive framework towards defining speech as a potential digital biomarker for dementia risk, and provide applications to regions experiencing increasing socioeconomic disparities.
Improvements in Heart Rate Variability among Dementia Family Caregivers Receiving a Home‐Visit Based Intervention: Preliminary Results from a Randomized Controlled Trial
Authors: Lee Jung‐Ah , Zhang Jiuchen , Sabino‐Laughlin Eilleen , Ju Eunae , Rahmani Amir , Qu Annie
Published: December 2023

Background

Emotional stress of family caregivers of persons with dementia (PWD) is often a topic of concern, as many experience negative health outcomes resulting from their years‐long caregiving role. A home‐visit based educational intervention focused on improving caregiving skills and managing stress was delivered to ethnically diverse dementia family caregivers in California in their preferred language. Previously, survey data were used to evaluate caregivers’ stress and well‐being. However, there might be limitations in using survey instruments to measure stress among diverse caregivers with limited English proficiency. Data collected via wearable technology (e.g., smartrings) can objectively measure stress in the form of Heart Rate Variability (HRV). We examined the intervention’s effect on stress levels measured by HRV among diverse dementia family caregivers using wearable technology.

Methods

The study design was a randomized controlled trial. Family caregivers of community dwelling PWD identifying as either Korean, Vietnamese, Hispanic/Latino, or Non‐Hispanic White were recruited through community outreach. Participants were randomly assigned with a 2:1 ratio to either the intervention group (IG) receiving language‐specific home‐visit based education or the attention control group (AG) receiving only care resource information. All participants wore smartrings monitoring HRV for 3 months. We used linear mixed models to assess the differences in HRV between the two groups using random intercept and slope for intervention, controlling for the covariates (age, gender, relationship, cohabitation, ethnicity, education).

Results

HRV data was collected from 59 caregivers (69% IG and 31% AG). Demographics included: 20 Korean (33.9%), 17 Vietnamese (28.8%), 10 Hispanic (17%), 12 Non‐Hispanic White (20.3%); 32 spouses (54%), 27 off‐spring (46%); 45 females (76%), ages 34 to 87 years (mean = 65.3, SD = 13.6). The linear mixed models showed a significant improvement in stress (higher HRV indicating better stress management) among IG caregivers compared to the AG caregivers over time (Beta coefficient = .079, P‐value = .032).

Conclusions

Measuring stress using smartrings was feasible and effective to track stress levels among diverse caregivers. Preliminary analyses suggest the home‐visit based intervention may have a positive effect on stress in ethnically diverse family caregivers of PWD compared to those only provided with care resource information.
Cytochrome P450 2C9 polymorphism in Puerto Rican Alzheimer’s patients and its role in the pharmacokinetics of THC and Melatonin (IGC‐AD1), an investigational drug
Authors: Rao Jagadeesh S , Gutierrez Evelyn , Grimaldi Claudia , De Jesus William Julio , Shahnawaz Saadia S , Mukunda Ram
Published: December 2023

Background

Alzheimer’s disease (AD) is a complex and chronic neurodegenerative illness. The AD patients were on many medications to manage their symptoms. Cytochrome P450 2C9 (CYP2C9) is the main enzyme involved in the metabolism of many drugs, including tetrahydrocannabinol (THC), which converts THC into the active metabolite 11‐hydroxy‐delta‐9‐THC metabolite. Individuals who lack CYP2C9 activity will have an increased risk of side effects from the drugs. CYP2C9 phenotypes are graded into groups, including poor (PM), intermediate (IM), normal (NM), and ultra‐rapid (UM) metabolizing phenotypes. IGC‐AD1 has major active ingredients that contain THC and melatonin.

Method

In our FDA‐regulated Phase‐1 trial, we evaluated a pilot study on the CYP2C9 polymorphism and pharmacokinetics of THC in AD patients (n = 12) from the Puerto Rican (PR) population as a safety measure. Using the Mass ARRAY Analyzer 4 instrument (Invitae Inc., MAA4, Agena, San Diego, CA), we determined the following CYP2C9 alleles: *2,*3,*4,*5,*6,*8,*11,*13,*15. We also investigate how polymorphism affects THC PK in IGC‐AD1 patients.

Result

In a Phase I clinical trial, we found that 62% of participants (n = 8) are carriers of at least one polymorphism. One participant has a rare heterozygous CYP2C9*1/*11 polymorphism. The participants with intermediate metabolizers (*1/*3 and *1/*2 allele) showed an increased half‐life of THC and an increased cMAX of OH‐THC compared to normal metabolizers (*1/*1). Participants who were intermediate metabolizers with *1/*2 variance had a lower AUC for THC levels. Altered CYP2C9 will affect the PK of THC and its metabolites.

Conclusion

Future studies should include a larger sample size of AD patients from PR and other regions, that will be allowing access to CYP2C9 genetic polymorphism in AD and understand the drug‐related adverse reactions associated with CYP2C9 genetic polymorphism. Polymorphism plays an important role in drug metabolism and should be considered as a part of dosing.
An Interplay between Health Equity and Disparity in Cognitive Decline
Authors: Wang Chen‐Pin , Gonzales Mitzi M. , Satizabal Claudia L. , Seshadri Sudha , Hazuda Helen
Published: December 2023

Background

Cognitive decline may be an early indicator of Alzheimer diseases and related dementia (ADRD). To identify the intervention targets that ameliorate disparities in ADRD, it is critical to employ disparity measures that account for health equity. We aimed to investigate disparity estimates in cognitive decline built on three health equity measures.

Method

The study sample (n = 451) was derived from the bi‐ethnic community‐dwelling San Antonio Longitudinal Study of Aging (SALSA). The latent variable mixture model classified cognitive function trajectory strata based on four repeated measures of the Mini Mental Status Examination (MMSE) over 8.5±1.3 years of follow‐up. Three risk adjustments were employed to optimize equity in social determinants of health (SDoH: income, education, social interactions) between Hispanics and non‐Hispanics. 1) Average constrained regression adjustment minimized the impact of SDoH for Hispanics. 2) Covariance constrained adjustment derived estimates with a near independence between the residuals with ethnicity. 3) Net compensation penalized regression imposed a penalty for excess lower MMSE among Hispanics. Inverse propensity score weighting (IPSW) estimates of disparity further adjusted away confounding due to covariates (demographics, disease burdens) between ethnic groups.

Result

Table 1 contrasted baseline characteristics of the study sample between Hispanics and non‐Hispanics. Two MMSE trajectory strata were identified: cognitive decline stratum (38%) with mean MMSE decreased from 23.9 to 21.2; and stable cognitive function stratum (62%) with mean MMSE around 28 throughout. Average constrained and covariance constrained risk adjustments attained optimal SDoH equity across three fairness metrics: predictive ratios, fair covariance, and net compensation (Table 2). Ethnic disparity in cognitive decline (Table 3) was strong conditioned on SDoH equity alone (log(aOR) = 4.27, p<0.001). Balancing covariates alone via IPSW without equity in SDoH also fell short for parity (aOR = 1.16, p<0.001). Parity in cognitive decline could be achievable under both SDoH equity and balanced covariates between ethnic groups (aOR = 0.85, p = 0.21).

Conclusion

Our study suggested that integrating equity metrices in ADRD disparity research could guide the paths to improve equity and reduce disparity. The field would be better served by identifying the causal drivers of disparities through the advancement in equity metrices and mediation analyses that delineate intricate interactions between SDoH and ADRD risk factors.
Plasma p‐tau forms as potential diagnostic biomarkers for Alzheimer’s disease
Authors: Kulczynska‐Przybik Agnieszka , Zetterberg Henrik , Blennow Kaj , Dulewicz Maciej , Ashton Nicholas J. , Karikari Thomas K , Mroczko Jan , Borawska Renata , Slowik Agnieszka , Mroczko Barbara
Published: December 2023

Background

Accumulation of tau aggregates is a pathological hallmark of Alzheimer’s disease (AD) that is closely related to the emergence of neurodegeneration and manifestation of clinical symptoms. Currently, CSF and plasma biomarkers of tau pathology, which would improve the diagnostic process in everyday clinical practice and facilitate the classification of patients for clinical trials, are the focus of research. Biomarkers of tau pathology correlate with post‐mortem AD pathology. Furthermore, they allow for differentiation of AD from other types of dementia, and prediction of future progression from normal cognition and mild cognitive impairment to AD. The availability of The clinical utility of novel assays for the detection of several isoforms of tau pathophysiology in the blood, which are currently available, requires verification. Therefore, the aim of the present study was evaluation of tau proteins in the blood of AD patients and non‐demented controls, and assessment of their diagnostic utility.

Method

Plasma concentrations of pTau181 and pTau231 were assessed using a Single molecule array (Simoa). CSF biomarkers, including Aβ‐42, Aβ‐42/Aβ‐40, tau and pTau181 were evaluated in 20 AD patients and 18 elderly subjects without cognitive deficits by ELISA technique.

Result

Statistically significantly higher blood levels of pTau181 and pTau231 were observed in AD patients in comparison to cognitively normal individuals. Increased concentration of pTau231 correlated with age and MMSE. Furthermore, the associations between the levels of plasma pTau231 and plasma pTau181, CSF Tau and pTau181, as well as Aβ‐42 were observed in the whole study group.

Conclusion

The results indicate that plasma P‐tau181 and P‐tau231 may be diagnostic biomarkers that can help to predict cognitive decline and that they hold promise for use in routine clinical practice.
Determinants of Cognitive Trajectories in Lower Educated Older Adults: Evidence from Brazil.
Authors: Ribeiro Fabiana , Duarte Yeda Aparecida de Oliveira , Leist Anja K.
Published: December 2023

Background

Patterns of cognitive change and modifiable factors for declining versus stable cognitive trajectories have rarely been described in a lower‐educated older population. Our goal was to identify heterogeneous long‐term trajectories of cognitive functioning and explore possible factors associated with cognitive decline beyond education, among older Brazilian adults.

Method

We used data on n = 1,042 adults aged ≥ 60 from the Health, Welfare and Aging (SABE) without cognitive impairment at baseline over four waves (2000‐2015) in São Paulo, Brazil. We applied group‐based trajectory modelling to identify cognitive trajectories. Cognition was measured using the abbreviated version of the Mini‐Mental State Examination (MMSE).

Result

We identified three cognitive groups: stable (n = 754), mild declining (n = 183), and strongly declining (n = 105). The probability of being in the strongly declining group membership was 10.7%. According to the MMSE classification, the mild declining group reached the average threshold for cognitive impairment on the last follow‐up, while the strongly declining group was on the second follow‐up. Furthermore, respondents in the stable trajectory were more likely to report more than primary education, to be white and married, to earn more than four times the minimum wage/month, to live in urban areas during childhood, and to practice vigorous physical activity at least three times a week. On the other hand, those in the strongly declining trajectory were more likely to identify as black or mixed, to self‐report subjective emptiness, and to have lower BMI, diabetes, and stroke. Moreover, both mild and strongly declining participants presented higher average age and lower MMSE scores at baseline compared to the stable trajectory. The multinomial logistic regression analysis revealed that respondents who self‐reported being mixed, had higher age, had primary education, had a stroke, and smoked at baseline were more likely to be in the strongly declining group.

Conclusion

Our findings suggest that besides education, interventions to reduce cognitive decline might include health and social policies addressing inequalities and modifiable risk factor burdens to improve later‐life cognitive functioning of at‐risk individuals. Sample attrition suggests estimates of the magnitude of the risk factors for cognitive decline to be conservative.
Survival and anti‐psychotic treatment in young onset Alzheimer’s disease
Authors: Stefanova Elka , Stojkovic Tanja , Stojmenovic Gorana Mandic , Šarčević Maksim , Obradovic Dragan , Kostic Vladimir S
Published: December 2023

Introduction

Psychosis and agitation represent a major therapeutic problem in young onset Alzheimer’s disease (YOAD), given that these symptoms pose a great risk to the patient, but treatment options are limited. Anti‐psychotic use is connected to different side effects, but increased mortality noted in older demented population is particularly worrying. Since YOAD patients are younger we wanted to examine if anti‐psychotic use is connected to decreased survival in these patients as well.

Aim

To examine the association between the use of anti‐psychotics and the length of survival in YOAD.

Material and methods

This is a retrospective study on 135 patients from Memory Center of Neurology Clinic, Clinical Center of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. do 01.04.2017. The need to introduce anti‐psychotics was noted during the follow‐up period and the difference in the survival of patients who at some point during the observation (from inclusion in the register until 2019) received anti‐psychotic therapy and those who did not. In this analysis we used Kaplan Meier survival analysis with log rank test with the time from the onset of symptoms to the outcome as an independent variable. Outcome was survived/died (at 2019.) and dependent variable was whether or not the patient received anti‐psychotics.

Results

During the period covered by this analysis, ending in 2019, among patients who received anti‐psychotics, 42 patients died while 20 remained alive. In patients who did not receive anti‐psychotics, 47 patients died while 26 remained alive. There was no statistically significant difference between the number of deaths in the group of patients who were and were not treated with anti‐psychotics (p = 0.682). Kaplan Meier analysis showed that the use of anti‐psychotics (at any point during observation) did not significantly affected survival measured as the time elapsed from the onset of symptoms to the outcome (death or 2019).

Conclusion

The use of anti‐psychotics in patients with YOAD is not associated with reduced lifespan.
Sleep‐Disordered Breathing and Cognition in a Diverse Population
Authors: Peltz Carrie , Bahorik Amber L , Leng Yue , Redline Susan , O'Bryant Sid E. , Yaffe Kristine
Published: December 2023

Background

Sleep‐disordered breathing (SDB) in older adults is associated with worse cognitive performance and dementia risk. Few studies have examined the relationship between SDB and cognition in a diverse population.

Methods

We studied 654 non‐demented participants from the Health and Aging Brain Study‐Health Disparities (HABS‐HD)‐Dormir study, with an in‐home sleep apnea assessment, a peripheral arterial tonometry‐based system (WatchPAT‐200). SDB measurements included: the respiratory event index (REI; 3% desaturation threshold) and the oxygen desaturation index (ODI; 4% threshold), split into mild (<15 events/hour) and moderate/severe (≥15 events/hour) and assessed by REM, non‐REM, and total sleep (via WatchPat algorithm). We examined three cognitive domains, defining worse cognition as negative standardized z‐scores on the Mini‐Mental Status Exam (MMSE; general cognition); the long‐delay Logical Memory and Spanish‐English Verbal Learning Test (memory); and Trails Making Test‐B and Digit Symbol Substitution (executive function). Regression analyses determined the association between SDB and cognition, adjusting for age, race, sex, education, diabetes, and hypertension.

Results

Participants were 42.7% Non‐Hispanic White, 35.4% Mexican‐American, and 21.9% Black, averaging 66.6 (sd = 8.2) years; 65.2% were female. The average sleep duration was 6.7 (sd = 1.3) hours; 50.4% had moderate/severe REI and 24.7% had moderate/severe ODI. Compared to mild REI, participants with moderate/severe had a trend towards worse executive function (total‐REI β = ‐0.09 (95% confidence intervals ‐0.20,0.01), p = 0.08). Moderate/severe total‐REI was not associated with global cognition (β = ‐0.02 (‐0.12,0.08), p = 0.75), but moderate/severe REM‐REI was (β = ‐0.11 (‐0.20,‐0.01), p = 0.04). Moderate/severe ODI was also associated with a trend towards worse executive function (total‐ODI β = ‐0.10 (‐0.22,0.01), p = 0.08) and global cognition (total‐ODI β = ‐0.11 (‐0.21,0.01), p = 0.06) compared to mild ODI. The association was greater in non‐REM‐ODI for global cognition (β = ‐0.14 (‐0.26,‐0.02), p = 0.02) and REM‐ODI for executive function (β = ‐0.12 (‐0.22,‐0.02), p = 0.02). There were no associations between REI/ODI and memory, and no interactions with race/ethnicity or APOE4 status. Results were similar after adjusting for body mass index.

Conclusions

In an ethnically and racially diverse population, we found that SDB was prevalent and moderate/severe SDB was associated with lower general cognition and executive function. Future studies should assess the relationship between REM/non‐REM SDB and cognition, and if SDB treatment may reduce dementia risk.
Time Together: An Intergenerational Respite, Mentorship and Training Program
Authors: Greenfield Felicia , Massimo Lauren , Kalafsky Megan , Morgan Brianna , Lynn Alison , Fein Leah
Published: December 2023

People living with dementia (PLWD) and their care partners (CP) experience physical and emotional stressors that are exacerbated by social isolation. Paying for in‐home respite care can be out of reach for many; the average cost of in‐home care is $28.00 with a three‐hour minimum. Furthermore, there is a critical gap in the dementia workforce (Weiss, 2020), leaving CP without access to affordable respite care, and PLWD without access to social engagement. The Penn Memory Center’s (PMC) Time Together (TT) and Weekly Smile (WS) programs are two low‐cost intergenerational respite and engagement programs that aim to increase social engagement for PLWD, reduce CP burden, and develop a geriatric care workforce. College students are trained to provide respite care and engagement for community‐dwelling PLWD and their CP. Families pay up to $10.00 (sliding scales offered) for up to 10 hours/week of companion/respite care. The student receives $10.00 an hour for their service. The PMC launched Time Together in 2019, delivering respite services in‐person. In 2020, the pandemic forced the program to pivot to a virtual model called WS. In January 2023 we began offering TT both in‐person and virtually to maximize accessibility and flexibility. Both the in‐person and virtual component are now called Time Together (TT).

To assess the impact of the WS model we used a mixed‐methods design, using qualitative and quantitative assessments. The exploratory qualitative arm used conventional content analysis methods to describe the experiences of PLWD, CP, and student participants through semi‐structured interviews. In our findings from interviews with 3 PLWD, 3 CP, and 3 student participants, PLWD cited meaningful engagement and improved mood. CPs described the importance of protected time for self‐care. Student respite workers appreciated learning about aging and dementia and especially enjoyed developing empathy and relational practice. Participation was mutually beneficial to all and created a lasting impact.

We continue to collect additional qualitative and quantitative to further evaluate findings from both the virtual and in‐person arms of Time Together for this updated abstract submission. Policy implications include recommendations for respite program structure and composition.