Creative Minds: San Francisco's Community Arts for Brain Health Initiative

Abstract Background The rising prevalence of age‐related neurocognitive disorders (NCDs) poses significant public health challenges, particularly in diverse urban populations with social and structural barriers to healthcare. Research suggests that social engagement and physical activity are key modifiable risk factors for dementia prevention. Creative Minds (CM), launched in 2020, is San Francisco's first neighborhood‐based arts initiative for brain health. CM is designed to mitigate social isolation and sedentarism in older adults by integrating artistic engagement with artist‐ and physician‐led workshops and educational activities, thereby promoting brain health literacy, socialization, and access to clinical care and research. Method CM is a community‐based program that provides culturally tailored, multilingual creative arts workshops in underserved neighborhoods of San Francisco in collaboration with the Global Brain Health Institute (GBHI) and community partners. Facilitated by professional artists , neurologists and geriatricians, CM engages participants in activities including visual arts, photography, dance, and storytelling. Educational components include physician‐led discussions on brain health, AD/ADRD risk factors, and discussions on the importance of participating in clinical research. Workshops are delivered in‐person and virtually, ensuring accessibility. Program effectiveness is assessed via pre‐ and post‐workshop surveys evaluating social engagement, health literacy, and willingness to participate in dementia prevention research. Result From 2020 to 2023, we conducted 280 CM workshops, reaching 156 older adults across multiple San Francisco neighborhoods. 70 educational sessions were delivered, with an increasing number of arts participants connected to AD/ADRD‐related research opportunities, demonstrated by a sample group of ten visual arts participants established in 2020 that has resulted in nine referrals and eight enrollments in brain health and aging research programs at the Memory and Aging Center, with deep characterizations including biomarkers. Preliminary CM survey data indicate improvements in self‐reported social connectedness, engagement in cognitively stimulating activities, and increased awareness of brain health practices. Additionally, CM's culturally tailored approach fostered greater engagement from monolingual and immigrant communities. Conclusion Community‐based arts engagement programs like CM offer a scalable, low‐cost intervention to promote brain health, address social determinants of AD/ADRD risk, and improve healthcare and research access in vulnerable populations. Future directions include expanding CM's reach and integrating additional evaluation measures.

AI‐Based Hyperspectral Retinal Imaging for Alzheimer’s Disease Detection: Preliminary Insights from the Bio‐Hermes‐002 Study

Abstract Background Artificial intelligence (AI)‐based retinal hyperspectral imaging (rHSI) represents a promising, non‐invasive approach to detecting Alzheimer’s disease (AD)‐related pathology, offering scalability and potential point‐of‐care utility. Prior findings from Bio‐Hermes‐001 demonstrated strong concordance between RetiSpec’s rHSI model and amyloid PET (Aβ‐PET). Bio‐Hermes‐002 builds on this work in a racially and clinically diverse cohort. While full rHSI performance data are forthcoming, we report preliminary participant characteristics relevant to real‐world deployment of retinal imaging technologies. Method Bio‐Hermes‐002 is an ongoing prospective, multi‐site study of ∼1,200 participants ( n =387enrolled at time of reporting) aged 60‐89 (mean 72.1), stratified into cognitively normal, MCI, and mild‐to‐moderate AD cohorts. Retinal imaging was performed using RetiSpec’s rHSI system. Amyloid and Tau PET imaging is ongoing; thus, analyses to date are descriptive. Comparative analysis with PET will be presented. Result Among enrolled participants, 57.4% were female and the cohort was both racially and ethnically diverse, with 18% of participants identifying as Hispanic or Latino and 19.4% identifying as non‐Caucasian. Notably, 19.4% of participants self‐reported eye conditions (e.g., n=25 cataracts, n=15 glaucoma, n=9 age‐related macular degeneration). Ophthalmologist review of images to confirm prevalence of comorbid eye conditions is forthcoming. The prevalence and distribution of eye conditions emphasizes the importance of validating retinal imaging tools in populations reflective of real‐world clinical settings, where such comorbidities are common. Feasibility assessments suggest that high‐quality retinal images were obtainable across a broad range of participants, including those with eye conditions (e.g., cataracts), supporting the applicability of AI‐based rHSI in heterogeneous clinical populations. Analysis of retinal image quality and its relationship to ocular health status will be presented alongside AI model performance data relative to gold standard PET scans. Conclusion Preliminary findings from Bio‐Hermes‐002 reinforce the feasibility of AI‐based retinal imaging in diverse and heterogeneous populations. Given the prevalence of ocular comorbidities such as cataracts, validation of retinal biomarkers under real‐world conditions is critical. Final results, including RetiSpec’s AI model performance against amyloid PET and comparative ensemble analyses, will be presented at the conference.

Improving longitudinal Aβ PET precision in the 1946 British birth cohort through anatomical consistency

Abstract Background Measuring Aβ change over time in cognitively unimpaired individuals is fundamental for preventative AD trials. The precision of longitudinal PET measurements may be enhanced through consistent anatomical labelling. Here we assessed the precision of cross‐sectional and longitudinal processing pipelines in a predominantly cognitively normal cohort. Method Participants enrolled in Insight 46 (1946 British birth cohort) underwent combined PET/MRI with [ 18 F]florbetapir at two timepoints ( n =324, interval=2.4±0.2yrs, Table 1). We compared four different processing pipelines with anatomical regions defined on T1w‐MRI. Figure 1 shows each pipeline variant, the cross‐sectional pipeline used the T1w‐MRI from each time‐point separately, whereas the longitudinal pipeline first created a subject‐specific midpoint T1w‐MRI (using SPM12), each with/without iterative‐Yang partial volume correction (PVC). Standard uptake value ratios (SUVRs) from each of the pipelines were computed with five reference regions: cerebellar grey matter (CGM), whole cerebellum (WC), subcortical white matter (WM), pons and a composite. SUVRs were converted to centiloids (CL) and annual rate of change (ARC) calculated. Reliable detection of Aβ accumulation was assessed using Gaussian mixture modelling (GMM) with the best fitting model from 1‐3 Gaussians assessed using Bayesian information criterion. Bimodal models were used to define reliable accumulation status as ARC>99th percentile of the lower component. Bootstrapping was used to calculate 95% CI for cut‐points and reliable accumulator status. GMM parameters were used to calculate a signal‐to‐noise ratio (SNR) for each method. Result ARC measured with WM and pons references, and the composite with PVC, did not show evidence of the expected bimodal distribution, instead best fitting a unimodal distribution, and were excluded from analysis. ARC from cross‐sectional and longitudinal pipelines were highly correlated for non‐PVC methods (rho>0.95, all reference regions) and slightly less correlated when PVC was used (CGM_PVC=0.80 and WC_PVC=0.88). Cut‐point estimates fell between 3.2 (WC_PVC, longitudinal) and 6.2 (CGM, cross‐sectional) CL/year. Precision of cut‐points and accumulator rate estimates were improved when using longitudinal processing with CGM_PVC and WC_PVC measures (Figure 2). Longitudinal processing boosted SNR substantially with CGM_PVC (cross‐sectional=1.0, longitudinal=1.9) and WC_PVC (cross‐ sectional=1.9, longitudinal=2.5; Figure 2E). Conclusion Longitudinally consistent anatomical region definitions enhance precision in estimating change when using cerebellum‐based reference regions with PVC.

The interactive influence of cortical amyloid levels and apathy symptoms on Digital Clock Test performance

Abstract Background The Digital Clock Test (DCT) is a novel, digitized version of the Clock Drawing Test that is sensitive to Alzheimer’s disease (AD) pathological burden (i.e., amyloid, tau) and cognitive impairment, yet provides a wealth of additional data. However, it is unclear how apathy, a common neuropsychiatric symptom often associated with AD pathology and cognitive decline, affects performance on the DCT. This study investigated the impact of apathy, alone and in combination with AD‐biomarkers, on DCT performance in older adults. Methods Participants ( n =102; mean age=77; 61% female; mean years education=16, 7 cognitively‐impaired) were from the Harvard Aging Brain Study (Table 1). Participants completed the DCT, self‐ and informant‐rated versions of the Apathy Evaluation Scale (AES; lower scores=greater apathy), and the self‐rated Geriatric Depression Scale (GDS) concurrently, then underwent amyloid (PiB) and tau (FTP) PET imaging within 18‐months of clinical assessments. Separate, cross‐sectional models examined self‐ and informant‐rated AES scores as predictors of DCT scores. Models were repeated with interactions between apathy and AD biomarkers (i.e., cortical amyloid aggregate and inferior temporal & entorhinal cortex tau) as primary predictors. All models controlled for age, sex, and education. Sensitivity analyses were run removing cognitively‐impaired participants and examining GDS scores as a covariate. Results AES scores did not predict DCT scores; however, the interaction between informant‐rated AES scores and PiB was predictive of DCT scores, such that individuals with higher PiB uptake and lower informant‐rated AES scores (indicating greater apathy) had lower DCT scores (Table 2; Figure 1). Results were unchanged when covarying for depression, but significance was lost when cognitively‐impaired participants were removed. Models with tau interactions were not significant, though the interaction with inferior temporal tau was trending. Conclusions In this sample of older adults, apathy symptoms alone did not impact DCT performance, though the presence of informant‐rated apathy symptoms and elevated amyloid burden together contributed to worse performance on the DCT, particularly in cognitively‐impaired individuals. This supports the use of the DCT as an efficient screening tool and highlights the need to further investigate the potential synergistic relationship between amyloid and apathy that could contribute to worse cognitive outcomes.

A phase‐II randomized controlled pilot and feasibility study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment

Abstract Background The decline of nicotinamide adenine dinucleotide (NAD + ) with aging may elevate risk of Alzheimer’s disease and related neurocognitive disorders (ADRD) by impairing cellular energy metabolism and reducing cerebral blood flow. Method We conducted a 12‐week double‐blind, randomized, placebo‐controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD + precursor, nicotinamide riboside (NR; 500 mg b.i.d.), for enhancing cognitive function and cerebral perfusion in older adults with mild cognitive impairment (MCI). Result 52 participants (33 females, 19 males) were randomized and 42 completed the trial (NR = 22, placebo = 20). Adherence was similar between groups (NR = 85 ± 20% vs. placebo = 91 ± 5%), with no serious adverse effects and comparable side effects. Blood NAD + increased with NR (pre: 23.36 ± 1.94; post: 48.52 ± 4.12 µM) compared with placebo (pre: 24.12 ± 1.70; post: 25.14 ± 1.58 µM) with a significant treatment by time interaction ( p <0.001). Cognitive function did not significantly improve, however, there was a modest increase in delayed recall memory from the WMS‐IV in the NR group (interaction p = 0.062). Perfusion of the left hippocampus increased with NR (pre: 51.7 ± 3.3; post: 58.0 ± 3.8 ml/min/100g) compared with placebo (pre: 55.6 ± 2.8; post: 51.7 ± 2.3 ml/min/100g; interaction p = 0.033); however, this was not associated with the change in memory performance. These outcomes were not strongly influenced by baseline plasma pTau‐217. Conclusion NR is well‐tolerated in older adults with MCI and may enhance perfusion of the hippocampus regardless of underlying AD pathology. However, this was not associated with improved memory performance in this short‐duration trial. A larger phase‐III trial over a longer treatment duration is warranted to determine the efficacy of NR for delaying cognitive impairment due to ADRD.

Advancing laboratory animal science in the Philippines: PALAS initiatives and partnerships leading to Asia Laboratory Animal Day 2025

Abstract As the Philippines celebrated the 2nd Asia Laboratory Animal Day (ALAD) last November 29, 2025, the Philippine Association for Laboratory Animal Sciences (PALAS) reflected on a year marked by growth, collaboration, and renewed commitment to ethical and scientific excellence in animal‐based research. Throughout 2025, PALAS has continued to strengthen the laboratory animal science community by advancing education, capacity building, policy advocacy, and regional cooperation. These efforts underscore PALAS’ vital role in shaping a culture of responsible animal research aligned with international standards.

Loss‐of‐Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder

Objective De novo variants in cullin‐3 ubiquitin ligase ( CUL3 ) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3 , describe the genotype–phenotype correlation, and investigate the underlying pathogenic mechanism. Methods Genetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient‐derived T‐cells. Results We assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss‐of‐function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin‐protein conjugates in vitro. Notably, we show that 4E‐BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient‐derived cells. Interpretation Our study further refines the clinical and mutational spectrum of CUL3 ‐associated NDDs, expands the spectrum of cullin RING E3 ligase‐associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2025;97:76–89

Perfusion and Electrophysiological Changes in MELAS

Punctate White Matter Abnormality in Moderate‐to‐Late Preterm Infants

Objective Moderate‐to‐late preterm (MLP) infants contribute to the greatest proportion of preterm children with neurodevelopmental impairments. White matter injury (WMI) is common and predicts adverse outcomes in very preterm (VP) infants. However, little is known about white matter abnormality (WMA) in MLP infants. We investigated the burden and distribution of WMA in MLP infants. Methods MLP infants were recruited from a randomized trial on neonatal nutrition and a prospective observational cohort in New Zealand, and underwent brain magnetic resonance imaging (MRI) soon after birth and at term‐equivalent age (TEA). WMA was manually segmented using an established method. Total and regional WMA volumes and percentage of WMA to total cerebral volume were calculated. Probabilistic WMA maps were generated and compared with WMI in VP infants and term infants with congenital heart disease. Results Of 101 infants (32 females), 40 (39.6%) had WMA on at least 1 scan. In 37 infants with WMA who had both scans, WMA was less visible in 22 (59.5%) or undetectable in 7 (18.9%) infants with a mean reduction of 72.7 ± 207.5 mm 3 in WMA volume from early‐life to term. Infants with and without WMA had mostly comparable pregnancy and neonatal characteristics. Probabilistic maps demonstrated a characteristic WMA topology, with most lesions in posterior followed by central and anterior regions. Trigonal areas were vulnerable across neonatal populations. Interpretation WMA is much more common in MLP infants than previously reported and occurs in a characteristic topology. WMA may be missed on TEA MRI, and its relationship with outcomes in MLP infants warrants attention. ANN NEUROL 2025;98:329–340

Unraveling C‐Selective Ring‐Opening of Phosphiranes with Carboxylic Acids and Other Nucleophiles: A Mechanistically‐Driven Approach

Abstract Phosphiranes are weak Lewis bases reacting with only a limited number of electrophiles to produce the corresponding phosphiranium ions. These salts are recognized for their propensity to undergo reactions with oxygen pronucleophiles at the phosphorus site, leading to the formation of phosphine oxide adducts. Building on a thorough mechanistic understanding, we have developed an unprecedented approach that enables the selective reaction of carboxylic acids, and other nucleophiles, at the carbon site of phosphiranes. This method involves the photochemical generation of highly reactive carbenes, which react with 1‐mesitylphosphirane to yield ylides. The latter undergoes a stepwise reaction with carboxylic acids, resulting in the production of the desired phosphines. In addition to DFT calculations, we have successfully isolated and fully characterized the key intermediates involved in the reaction.