This is a new paper from Florey Institute presenting a new imaging method relating to cognition, which is important when evaluating possible effects of drug candidates for AD. ATH has several of them as we know.

This chapter from the intro seems to me important:
"Sodium ion concentrations are compartmentalized and tightly regulated in normal cell homeostasis; the transmembrane gradient is actively maintained by the highly energy-consuming sodium-potassium ATPase. Cell death and resulting loss of cell membrane integrity, sodium-potassium pump dysfunction, sodium channel up/downregulation, other interlinked membrane or ionic/metabolic alterations (such as calcium8), and extracellular changes all affect brain tissue sodium values. Preclinical studies also support a role of these metabolic perturbations in the pathophysiology of AD.9-12 In-vivo human sodium-MRI brain studies have furthermore shown differences between control and Ad groups,13-16 stable sodium values across normal ageing,17 and differences in functional disability metrics for Alzheimer’s disease and other neurodegenerative conditions compared to controls.15,16,18,19 Sodium-MRI has also been shown to be predictive of Montreal Cognitive Assessment scores in AD.15,16"

If ATH434 could help in this matter, perhaps it could be eliminating iron from mitochondria hampering energy production (??)

Here you can read the paper: https://academic.oup.com/braincomms/article/6/5/fcae307/7755132?login=false

Brain Commun

. 2024 Sep 11;6(5):fcae307.

doi: 10.1093/braincomms/fcae307. eCollection 2024.

3T sodium-MRI as predictor of neurocognition in nondemented older adults: a cross sectional study

Elaine Lui ^{1 2}, Vijay K Venkatraman ^{1 2}, Sue Finch ³, Michelle Chua ², Tie-Qiang Li ⁴, Bradley P Sutton ^{5 6}, Christopher E Steward ^{1 2}, Bradford Moffat ¹, Elizabeth V Cyarto ⁷, Kathryn A Ellis ^{8 9}, Christopher C Rowe ^{10 11}, Colin L Masters ¹¹, Nicola T Lautenschlager ^{8 12}, Patricia M Desmond ^{1 2}

Affiliations Expand

• PMID: 39318783

PMCID: PMC11420980 DOI: 10.1093/braincomms/fcae307

Abstract

Dementia is a burgeoning global problem. Novel magnetic resonance imaging (MRI) metrics beyond volumetry may bring new insight and aid clinical trial evaluation of interventions early in the Alzheimer's disease course to complement existing imaging and clinical metrics. To determine whether: (i) normalized regional sodium-MRI values (Na-SI) are better predictors of neurocognitive status than volumetry (ii) cerebral amyloid PET status improves modelling. Nondemented older adult (>60 years) volunteers of known Alzheimer's Disease Assessment Scale (ADAS-Cog11), Mini-Mental State Examination (MMSE) and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test scores, ApolipoproteinE (APOE) e4 +/- cerebral amyloid PET status were prospectively recruited for 3T sodium-MRI brain scans. Left and right hippocampal, entorhinal and precuneus volumes and Na-SI (using the proportional intensity scaling normalization method with field inhomogeneity and partial volume corrections) were obtained after segmentation and co-registration of 3D-T1-weighted proton images. Descriptive statistics, correlation and best-subset regression analyses were performed. In our 76 nondemented participants (mean(standard deviation) age 75(5) years; woman 47(62%); cognitively unimpaired 54/76(71%), mildly cognitively impaired 22/76(29%)), left hippocampal Na-SI, not volume, was preferentially in the best models for predicting MMSE (Odds Ratio (OR) = 0.19(Confidence Interval (CI) = 0.07,0.53), P-value = 0.001) and ADAS-Cog11 (Beta(B) = 1.2(CI = 0.28,2.1), P-value = 0.01) scores. In the entorhinal analysis, right entorhinal Na-SI, not volume, was preferentially selected in the best model for predicting ADAS-Cog11 (B = 0.94(CI = 0.11,1.8), P-value = 0.03). While right entorhinal Na-SI and volume were both selected for MMSE modelling (Na-SI OR = 0.23(CI = 0.09,0.6), P-value = 0.003; volume OR = 2.6(CI = 1.0,6.6), P-value = 0.04), independently, Na-SI explained more of the variance (Na-SI R ² = 10.3; volume R ² = 7.5). No imaging variable was selected in the best CERAD models. Adding cerebral amyloid status improved model fit (Akaike Information Criterion increased 2.0 for all models, P-value < 0.001-0.045). Regional Na-SI were more predictive of MMSE and ADAS-Cog11 scores in our nondemented older adult cohort than volume, hippocampal more robust than entorhinal region of interest. Positive amyloid status slightly further improved model fit.