Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer's disease.

Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer's disease (AD) and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) positron emission tomography (PET), but most inflammation PET tracers cannot image subjects with a low-binder TSPO rs6971 genotype. In an important development, participants with any TSPO genotype can be imaged with a novel tracer, [11C]ER176, that has a high binding potential and a more favorable metabolite profile than other TSPO tracers currently available. We applied [11C]ER176 to detect brain inflammation in mild cognitive impairment (MCI) caused by early-onset AD. Furthermore, we sought to correlate the brain localization of inflammation, volume loss, elevated Aß and tau. We studied brain inflammation in 25 patients with early-onset amnestic MCI (average age 59 ± 4.5 years, 10 women) and 23 healthy controls (average age 65 ± 6.0 years, 12 women), both groups with a similar proportion of all three TSPO-binding affinities. [11C]ER176 total distribution volume (VT), obtained with an arterial input function, was compared across patients and controls using voxel-wise and region-wise analyses. In addition to inflammation PET, most MCI patients had Aß (n=23), and tau PET (n=21). For Aß and tau tracers, standard uptake value ratios (SUVRs) were calculated using cerebellar grey matter as region of reference. Regional correlations among the three tracers were determined. Data were corrected for partial volume effect. Cognitive performance was studied with standard neuropsychological tools. In MCI caused by early-onset AD, there was inflammation in the default network, reaching statistical significance in precuneus and lateral temporal and parietal association cortex bilaterally, and in the right amygdala. Topographically, inflammation co-localized most strongly with tau (r= 0.63 ± 0.24). This correlation was higher than the co-localization of Aß with tau (r= 0.55±0.25) and of inflammation with Aß (0.43±0.22). Inflammation co-localized least with atrophy (-0.29±0.26). These regional correlations could be detected in participants with any of the three rs6971 TSPO polymorphisms. Inflammation in AD-related regions correlated with impaired cognitive scores. Our data highlight the importance of inflammation, a potential therapeutic target, in the AD process. Furthermore, they support the notion that, as shown in experimental tissue and animal models, the propagation of tau in humans is associated with brain inflammation.

Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup.

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.

Visual and Refractive Outcomes After Bi-aspheric Trifocal Toric Diffractive Intraocular Lens Implantation.

PURPOSE: To assess clinical outcomes after cataract surgery with bilateral implantation of a new bi-aspheric diffractive intraocular lens (IOL). METHODS: Thirty patients underwent bilateral implantation of the Asqelio Trifocal Toric IOL (AST Products, Inc) and were evaluated 3 months postoperatively. Main outcomes included refractive error, photopic monocular and binocular uncorrected and corrected distance (UDVA, CDVA), intermediate (UIVA, CDIVA) at 60 cm, and near (UNVA, CDNVA) at 40 cm visual acuities. Mesopic monocular and binocular CDNVA were also measured. Defocus curves, binocular contrast sensitivity under photopic and mesopic conditions with and without glare and rotational stability were determined. Patients completed Catquest-9SF and visual symptoms questionnaires. RESULTS: Average values of binocular photopic CDVA, CDIVA, and CDNVA, and mesopic CDNVA were -0.04 ± 0.06, 0.02 ± 0.08, 0.02 ± 0.07, and 0.22 ± 0.11 logMAR, respectively. All patients achieved cumulative CDVA ⩾ 20/25, and CDIVA and CDNVA of 20/32 or better. Binocular depth of focus was approximately 3.25 diopters (D). Mean postoperative spherical equivalent was -0.08 ± 0.26 D, with 95% of eyes within ±0.50 D. Mean postoperative refractive cylinder was -0.22 ± 0.27 D, with 91.67% of eyes within 0.50 D or less, respectively. IOL rotation averaged 0.25 ± 0.65 degrees, all eyes having rotation of less than 5 degrees. Contrast sensitivity was within or above normal levels under photopic and mesopic conditions, with or without glare, except for 12 cpd under mesopic conditions with glare. Questionnaire responses indicated 96.67% of patients were satisfied or very satisfied with postoperative vision, and 80.00% to 96.67% reported no difficulty in different daily activities. CONCLUSIONS: The Asqelio Trifocal Toric IOL demonstrated favorable outcomes, providing excellent visual performance at all distances, precise refractive results, and remarkable rotational stability. Patients reported high satisfaction levels and minimal difficulty in daily activities. [J Refract Surg. 2024;40(6):e407-e419.].

Accuracy and safety of freehand vs. end-on fluoroscopic guided drill-hole placement in canine cadaveric thoracic, lumbar and sacral vertebrae.

Objective: To develop and evaluate the safety and accuracy of an open, end-on fluoroscopic guided (EOFG) drill hole position technique in canine cadaveric spinal surgery, in comparison to a traditional free-hand (FH) drilling technique. Study design: Cadaveric comparison study. Animals: Canine cadaveric vertebral columns (n = 4). Methods: Computed tomography (CT) scans were performed for in-silico planning. Ideal implant purchase depth and angulations were determined from previously published data. Plans for end-on fluoroscopic guided drill holes included angled reconstructions in thick slab mode to mimic fluoroscopic images. Following surgical preparation of T8 to S2, holes were drilled by one of two experienced surgeons randomized evenly by operated side, surgeon, and technique. C-arm fluoroscopy was utilized for the end-on technique. CT was repeated after the procedures. Safety was determined categorically using a modified Zdichavsky classification and "optimal" placement was compared between techniques. Continuous data for drill-hole accuracy was calculated as angle and depth deviations from the planned trajectories. Data sets were analyzed at both univariable and multivariable levels with logistic regression analysis. Results: Drill hole safety was categorized as optimal (modified Zdichavsky classification 1) in 51/60 (85%) of drill holes using EOFG and 33/60 (55%) using FH (P < 0.001) techniques. There were no "unsafe" holes (modified Zdichavsky classification 3a). Optimal drill hole placement was significantly associated with the EOFG technique and use of the largest cadaver, and was significantly less likely within the thoracic region. Mean angle and depth deviations were significantly lower with the EOFG technique. Angle deviations were significantly lower for EOFG in the lumbar region, whereas bone purchase deviations were significantly lower for EOFG in both the thoracic and lumbar regions. The mean time taken to drill the hole was significantly longer for the EOFG technique. Conclusion: Optimal drill hole placement was significantly more likely with the EOFG technique and improved the accuracy of bone purchase in the thoracic region. Clinical significance: The EOFG technique shows promise for translation into a clinically setting, potentially improving implant purchase and therefore stabilizing construct strength, whilst potentially reducing the likelihood of neurovascular injury and need for surgical revision.

TRIM35 Monoubiquitinates H2B in Cardiac Cells, Implications for Heart Failure.

BACKGROUND: The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with accessibility to its transcriptional promoter sites remains unresolved, especially in the setting of mature terminally differentiated (nonreplicative) cardiomyocytes. METHODS: Male and female control or TRIM35 (tripartite motif containing 35) overexpression adolescent (aged 1-3 months) and adult (aged 4-6 months) transgenic mice were used for all in vivo experiments. Primary adolescent or adult mouse cardiomyocytes were isolated from control or TRIM35 overexpression transgenic mice for all in vitro experiments. Adenovirus or small-interfering RNA was used for all molecular experiments to overexpress or knockdown, respectively, target genes in primary mouse cardiomyocytes. Patient dilated cardiomyopathy or nonfailing left ventricle samples were used for translational and mechanistic insight. Chromatin immunoprecipitation and DNA sequencing or quantitative real-time polymerase chain reaction (qPCR) was used to assess P53 binding to its transcriptional promoter targets, and RNA sequencing was used to identify disease-specific signaling pathways. RESULTS: Here, we show that E3-ubiquitin ligase TRIM35 can directly monoubiquitinate lysine-120 (K120) on histone 2B in postnatal mature cardiomyocytes. This epigenetic modification was sufficient to promote chromatin remodeling, accessibility of P53 to its transcriptional promoter targets, and elongation of its transcribed mRNA. We found that increased P53 transcriptional activity (in cardiomyocyte-specific Trim35 overexpression transgenic mice) was sufficient to initiate heart failure and these molecular findings were recapitulated in nonischemic human LV dilated cardiomyopathy samples. CONCLUSIONS: These findings suggest that TRIM35 and the K120Ub-histone 2B epigenetic modification are molecular features of cardiomyocytes that can collectively predict dilated cardiomyopathy pathogenesis.

WhatsApp-based intervention in urban Colombia to support the prevention of arboviral diseases: a feasibility study.

Arboviral diseases remain a significant health concern worldwide, with over half the world's population at risk for dengue alone. Without a vaccine or targeted treatment, the most effective strategy of prevention is vector management with community involvement. mHealth interventions, like WhatsApp, offer promising results for engaging communities and promoting healthier behaviors. This study explores the feasibility of integrating WhatsApp in vector control activities to improve arbovirus prevention in Colombia. A mixed-methods approach was employed to assess the WhatsApp-based intervention. WhatsApp messages were sent to 45 community women for 5 weeks to increase their knowledge and practices about dengue, Zika, and chikungunya. Pre-and-post surveys and focus group discussions were conducted in community settings to measure the feasibility and acceptability of this intervention. Chat reviews were done to assess the usability of users. A total of 1566 messages were exchanged in 45 WhatsApp chats. High acceptance and good usability (82% of users used the app for replying) were reported in this study. WhatsApp messages were perceived as short, clear, and enjoyable. Users liked the frequency, and design of messages. Pre- and post-surveys demonstrated improvements in the knowledge and practices of arboviral diseases. The intention to apply this knowledge in practice was reflected in a significant improvement, particularly in cleaning the laundry tank once a week (pre 62.1% to post 89.6%, p < 0.008). This study suggests that using WhatsApp as an additional tool could be a feasible, acceptable, and affordable strategy for improving the adoption of better practices in the prevention of arboviral diseases.

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Exploring the composition and properties of Centella asiatica metabolites and investigating their impact on BSA glycation, LDL oxidation and α-amylase inhibition.

Centella asiatica (L.) Urb. is a small herbaceous plant belonging to the Apiaceae family that is rich in triterpenes, such as asiaticoside and madecassoside. Centella asiatica finds broad application in promoting wound healing, addressing skin disorders, and boosting both memory and cognitive function. Given its extensive therapeutic potential, this study aimed not only to investigate the Centella asiatica ethanolic extract but also to analyze the biological properties of its organic fractions, such as antioxidant antiglycation capacity, which are little explored. We also identified the main bioactive compounds through spectrometry analysis. The ethanolic extract (EE) was obtained through a static maceration for seven days, while organic fractions (HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; BF: n-butanol fraction and HMF: hydromethanolic fraction) were obtained via liquid-liquid fractionation. The concentration of phenolic compounds, flavonoids, and tannins in each sample was quantified. Additionally, the antiglycation (BSA/FRU, BSA/MGO, and ARG/MGO models) and antioxidant (FRAP, ORAC, and DPPH) properties, as well as the ability to inhibit LDL oxidation and hepatic tissue peroxidation were evaluated. The inhibition of enzyme activity was also analyzed (α-amylase, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase). We also evaluated the antimicrobial and cytotoxicity against RAW 264.7 macrophages. The main compounds present in the most bioactive fractions were elucidated through ESI FT-ICR MS and HPLC-ESI-MS/MS analysis. In the assessment of antioxidant capacity (FRAP, ORAC, and DPPH), the EAF and BF fractions exhibited notable results, and as they are the phenolic compounds richest fractions, they also inhibited LDL oxidation, protected the hepatic tissue from peroxidation and inhibited α-amylase activity. Regarding glycation models, the EE, EAF, BF, and HMF fractions demonstrated substantial activity in the BSA/FRU model. However, BF was the only fraction that presented non-cytotoxic activity in RAW 264.7 macrophages at all tested concentrations. In conclusion, this study provides valuable insights into the antioxidant, antiglycation, and enzymatic inhibition capacities of the ethanolic extract and organic fractions of Centella asiatica. The findings suggest that further in vivo studies, particularly focusing on the butanol fraction (BF), may be promising routes for future research and potential therapeutic applications.

COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum.

Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

Genome-wide identification and comparative analysis of the Amino Acid Transporter (AAT) gene family and their roles during Phaseolus vulgaris symbioses.

Amino acid transporters (AATs) are essential integral membrane proteins that serve multiple roles, such as facilitating the transport of amino acids across cell membranes. They play a crucial role in the growth and development of plants. Phaseolus vulgaris, a significant legume crop, serves as a valuable model for studying root symbiosis. In this study, we have conducted an exploration of the AAT gene family in P. vulgaris. In this research, we identified 84 AAT genes within the P. vulgaris genome sequence and categorized them into 12 subfamilies based on their similarity and phylogenetic relationships with AATs found in Arabidopsis and rice. Interestingly, these AAT genes were not evenly distributed across the chromosomes of P. vulgaris . Instead, there was an unusual concentration of these genes located toward the outer edges of chromosomal arms. Upon conducting motif analysis and gene structural analysis, we observed a consistent presence of similar motifs and an intron-exon distribution pattern among the subfamilies. When we analyzed the expression profiles of PvAAT genes, we noted tissue-specific expression patterns. Furthermore, our investigation into AAT gene expression under rhizobial and mycorrhizal symbiotic conditions revealed that certain genes exhibited high levels of expression. Specifically, ATLa5 and LHT2 was notably upregulated under both symbiotic conditions. These findings point towards a potential role of AATs in the context of rhizobial and mycorrhizal symbiosis in P. vulgaris, in addition to their well-established regulatory functions.

Clinical Outcomes of a Bi-Aspheric Trifocal Diffractive Intraocular Lens.

Purpose: To assess refractive and visual outcomes post-cataract surgery with bilateral implantation of a bi-aspheric diffractive trifocal intraocular lens (IOL). Methods: A total of 24 patients who underwent bilateral implantation with the Asqelio Trifocal IOL TFLIO130C were evaluated at the 6 months postoperative mark. Key outcome measures included refractive error, photopic monocular and binocular uncorrected and corrected distance visual acuity (UDVA, CDVA), uncorrected and corrected intermediate visual acuity (UIVA, CDIVA) at 60 cm, and uncorrected and corrected near visual acuity (UNVA, CDNVA) at 40 cm. Additionally, monocular and binocular CDNVA were assessed under mesopic conditions. Monocular and binocular defocus curves, and binocular contrast sensitivity under photopic and mesopic conditions, with and without glare, were measured. Catquest-9SF and visual symptoms questionnaires were also administered. Results: Postoperative average values of binocular logMAR photopic CDVA, photopic CDIVA, photopic CDNVA and mesopic CDNVA were -0.01±0.06, 0.03±0.09, 0.02±0.05 and 0.19±0.13, respectively. About 100% of patients showed cumulative CDVA and CDNVA ≥20/25, and CDIVA ≥20/32. The average absolute depth-of-focus was about 4.50D. The average postoperative spherical equivalent was 0.05±0.30D and 100% and 93.75% eyes were within ±1.00D and ±0.50D, respectively. Contrast sensitivity was either within or above normal levels under both photopic and mesopic conditions, both with and without glare, except for 12 cpd under mesopic conditions with glare where the mean falls just below the normal range. Questionnaires revealed that 87.5% of patients were either satisfied or very satisfied with their vision after the surgery, and higher percentages for no difficulty in performing different activities, ranging from 70.83% to 95.83%, were reported. Conclusion: This study demonstrates that the bi-aspheric diffractive trifocal IOL yields very good visual performance across distances, fostering high satisfaction levels and minimal difficulties in daily activities.

Comparison of Metabolic, Lifestyle and Mental Health Parameters in People with Diabetes and Relatives with and without Family Support.

Purpose: To analyze and compare metabolic, lifestyle and mental health parameters in relatives and people-with-T2DM (PDM) with and without support. Patients and Methods: We included 160 patients with <5 years of diagnosis of T2DM, without disabling complications, and non-smokers, attending a multidisciplinary program for diabetes control, and their accompanying relatives. If the patients or relatives abandoned the program, we contacted them and asked to take laboratory tests and answer surveys regarding anxiety, depression, and perception of their family support. Variables distribution was assessed with the Kolmogorov-Smirnov test. We used ANOVA or Kruskal Wallis Tests, according to variable distribution. Frequencies and percentages are used for categorical values and analyzed with a chi-square test. We separated the participants in four groups: relatives with and without support and PDM with and without support. Results: We included 160 participants, age 51±10, and 54.3% women. Total cholesterol (188±36 vs 204±43 vs 170±34 vs 181±35 mg/dL, p=0.001), LDL-cholesterol (113±35 vs 125±27 vs 101 ±30 vs 109±29, p=0.008), and non-HDL cholesterol (143±32 vs 154 ±30 vs 129±33 vs 135±35 mg/dL, p=0.010) were higher in the group without support. Although patients without family support had lower values, they did not achieve metabolic goals. Weight (75±17 vs 77±19 vs 74.2±10.5 vs 90.2±17.3 kg) and body mass index (28.9±4.8 vs 30.1±4.7 vs 27.4±3.3 vs 33±4.3 kg/m2) were higher in PDM without family support (p<0.001 for both). Conclusion: Support in PDM and their families is important in metabolic control. However, raising awareness among family members to screen for diabetes and changes in lifestyle are points to improve. Including the evaluation of social and family support will allow a more complete assessment to identify barriers to achieving goals.

Novel avenues of tau research.

INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

BACKGROUND: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. METHODS: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. RESULTS: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. DISCUSSION: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.