Citations

Abstract INTRODUCTION Primary age‐related tauopathy (PART) is defined by neurofibrillary tangles (NFTs) with absent‐minimal amyloid beta (Aβ) plaques. Currently, definitive diagnosis of PART occurs with autopsy. This study investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography (FDG‐PET) could detect PART‐related metabolic changes and assessed the impact of common co‐pathologies. METHODS We performed a retrospective cross‐sectional study of 88 individuals (mean age 85.6) with autopsy‐confirmed PART (Braak I to IV; Thal phases 0 to 2) who underwent ante mortem FDG‐PET. Visual ratings and standardized uptake value ratios (SUVRs) were analyzed in medial and lateral temporal lobes, inferior temporal pole, precuneus, and posterior cingulate regions. RESULTS Medial temporal hypometabolism was observed in PART, in the presence of co‐pathologies. Argyrophilic grain disease and TAR DNA‐binding protein 43 were associated with greater hypometabolism ( p < 0.01). Lewy body disease affected parietal regions. DISCUSSION FDG‐PET reveals that PART‐related hypometabolism occurs when co‐pathologies are present, but PART alone appears to have minimal effect on medial temporal lobe hypometabolism. Highlights FDG‐PET hypometabolism worsens with Braak NFT stage. FDG‐PET detects mild lateral temporal lobe hypometabolism in PART alone. PART alone has a minimal effect on medial temporal lobe hypometabolism. Medial temporal hypometabolism is worse in PART with TDP‐43 and especially AGD. The presence of LBD contributes to parietal hypometabolism on FGD‐PET in PART.

Abstract BACKGROUND First held in 2020, the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT‐AD) is a program to train the next generation of Alzheimer's disease (AD) and related dementias (AD/ADRD) clinical trialists. METHODS IMPACT‐AD includes didactic, workshop, and small group components. RESULTS IMPACT‐AD has trained 18 alumni–scholars (accepted from 424 applicants), of whom 67% were female. Forty‐eight (26%) were the first in their family to attend college. Scholars included individuals from all racial and ethnic groups. Each year, participants demonstrated increased learning about AD/ADRD clinical trials through a pre/post‐test model of knowledge assessments. Among those completing annual follow‐up surveys, >84% remain in AD/ADRD trials careers, and 80% have experienced career advances or milestones. In the latter group, > 90% indicated that participating in IMPACT‐AD contributed to this career growth. DISCUSSION IMPACT‐AD is a novel educational program that is achieving its goals. Highlights Over 5 years, the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT‐AD) has trained 188 scholars. The course has been accessible to a broad range of trainees who were diverse in professional and demographic backgrounds. Objective assessments indicate that participants gain knowledge through participation. Eighty‐four percent of trainees have remained in Alzheimer's disease and related dementias (ADRD) trials careers. Eighty percent of alumni have experienced career advances; nearly all indicated that participating in the course contributed to their success.

Abstract INTRODUCTION When cerebrospinal fluid (CSF) and positron emission tomography (PET) measurements for amyloid‐beta‐peptide (Aβ) related pathology are discordant, therapeutic decision‐making becomes uncertain. METHODS Using data from patients with mild cognitive impairment ( n = 541) from the Alzheimer's Disease Neuroimaging Initiative, we examined baseline characteristics and longitudinal clinical outcomes in persons grouped according to normal/abnormal Aβ via concurrent CSF and PET determinations using standard cutpoints. RESULTS Discordant groups for brain Aβ status (CSF+/PET− and CSF−/PET+) each represented about 5% of the mild cognitive impairment (MCI) population. Longitudinally, neither discordant group declined more than the CSF−/PET− group on either a memory measure or the Clinical Dementia Rating Sum of Boxes scores over a median 4 years of observation, while the CSF+/PET+ group exhibited worsening on both measures. DISCUSSION In contrast to the clinical decline observed in the CSF+/PET+ group, persons with MCI and CSF+/PET− or CSF−/PET+ brain amyloid patterns did not exhibit incipient decline. Highlights Discrepant abnormal cerebrospinal fluid (CSF) and positron emission tomography (PET) brain amyloid indicators are uncommon in mild cognitive impairment (MCI). CSF‐PET discrepant persons with MCI tend to have less abnormal values initially. CSF‐PET discrepant persons with MCI have a benign prognosis at 4 years.

AbstractINTRODUCTIONWe investigated the usefulness of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for capturing vascular cognitive impairment (VCI) in the context of amyloidosis.METHODSUsing two independent cohorts (n = 1810), we assessed the relationship of plasma NfL and GFAP with (1) vascular brain indices; (2) diagnostic states using the following definitions: vascular versus not (white matter hyperintensity/total intracranial volume ≥ 1.3%), and cognitively impaired (CI) versus cognitively unimpaired (CU) using Clinical Dementia Rating ([CDR] scale ≥ 0.5); and (3) their upstream predictors using structural equation models (SEMs).RESULTSPlasma NfL and GFAP were associated with vascular brain damage and differed across states (VCI > vascular CU > non‐vascular CI > non‐vascular CU). In a population‐based sample, these biomarkers distinguished vascular CU and VCI from non‐vascular CU groups with greater separation in amyloid negative participants. Pathway analyses showed NfL was primarily influenced by systemic/brain vascular health, whereas amyloid contributed to GFAP variability.DISCUSSIONPlasma biomarkers, particularly NfL, capture vascular brain changes and show promise for VCI identification.Highlights Plasma NfL and glial fibrillary acidic protein (GFAP) were associated with vascular brain indices. Plasma biomarkers differed across diagnostic states (VCI > vascular CU > non‐vascular CI > non‐vascular CU). Plasma markers discriminated vascular from non‐vascular states with greater separation in Aβ− participants. NfL was linked to vascular health, while amyloid influenced GFAP variability in the population‐based sample. Future longitudinal frameworks should consider systemic inflammation markers along with these plasma markers to better understand VCID‐related brain changes and cognitive decline.

Abstract Objective To compare iron deposition in the substantia nigra (SN) as measured with quantitative susceptibility mapping (QSM) on antemortem magnetic resonance imaging (MRI) between individuals with and without Lewy‐related pathology at autopsy. Methods We performed a retrospective cohort study including 54 participants who underwent autopsy and antemortem MRI with QSM. Cases were classified as Lewy body disease (LBD)‐present (n = 13) if they had Lewy‐related pathology and LBD‐absent (n = 41) if they did not have Lewy‐related pathology. QSM was calculated for the whole SN and the two subregions: pars compacta (SNc) and pars reticulata (SNr). Nonparametric Wilcoxon rank‐sum tests were used to compare SN QSM values between LBD‐present and LBD‐absent cases. Area under the receiver operating characteristic (ROC) curve (AUC) analyses tested the accuracy of SN QSM values to distinguish the two groups. Associations of QSM values in the SN and its subregions with clinical features were tested with Spearman's correlations. Results The LBD‐present group had higher QSM values in the SNc ( P = 0.008) than the LBD‐absent group with no differences in SNr. QSM values of the SNc distinguished LBD‐present and LBD‐absent cases with good accuracy (AUC = 0.74) and correlated with the presence of parkinsonism and parkinsonism severity. Conclusions This study provides neuropathological confirmation of the utility of SNc QSM as an in vivo biomarker of Lewy‐related pathology. Imaging evidence of abnormal iron deposition in the SNc could potentially serve as a biomarker for inclusion in emerging research frameworks aimed at defining individuals with LBD based on their biological characteristics. Ultimately, this could facilitate more precise diagnoses and guide treatment strategies in LBD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.