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Cognitive and neurodegenerative profile differences between “mismatch MCI” (A+T‐N+ MCI) And “prodromal AD” (A+T+N+ MCI) increase with time
Author(s) -
McCollum Lauren,
Das Sandhitsu R.,
Wang Jieqiong,
Xie Long,
de Flores Robin,
Wisse Laura,
Xie Sharon X.,
Yushkevich Paul,
Wolk David A.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046030
Subject(s) - neurodegeneration , psychology , dementia , alzheimer's disease , temporal lobe , neuroscience , cognitive decline , audiology , medicine , disease , epilepsy
Background Per the Amyloid/Tau/Neurodegeneration (A/T/N) framework, beta‐amyloid accumulates during preclinical Alzheimer’s Disease (AD), followed by tau, then neurodegeneration. As AD symptoms are most linked to tau and neurodegeneration, both are expected by the MCI stage of disease. Thus, A+T‐N+ MCI (“mismatch MCI”) is thought to have both AD pathophysiology and non‐AD pathology, with the latter (given absence of tau) driving neurodegeneration and symptoms. We investigate the cognitive and neurodegenerative profile of mismatch MCI compared to “standard” A+T+N+ MCI (“prodromal AD”). Method A+ (by CSF) and N+ (by hippocampal volume <90 th ‐percentile for A+ dementia) MCI patients from ADNI2/GO were grouped by tau status (based on CSF p‐tau): mismatch MCI (T‐; n=44; 34 followed longitudinally) and prodromal AD (T+; n=84; 61 followed longitudinally) (Table 1). Baseline AVLT immediate‐memory first trial, AVLT delayed recall, animal naming (category fluency), and Trails‐B‐minus‐Trails‐A (executive function; log‐transformed) z‐scores were compared. Longitudinal cognition was analyzed using mixed‐effects models. A Kaplan‐Meier analysis compared dementia‐free survival. Whole‐brain voxel‐wise analyses compared cortical thicknesses of each MCI group to A‐ controls. Medial temporal lobe (MTL) subregion volumes, determined using ASHS‐T1 (Xie, 2019) on T1‐weighted MRI, were compared at baseline and longitudinally. Result Mismatch MCI had less baseline delayed‐recall impairment (Figure 1), but was similar on other domains. Time*group interaction terms for longitudinal cognition were all significant (p<0.05), indicating slower decline in mismatch MCI (Figure 2). Mismatch MCI had longer dementia‐free survival (Figure 3, p<0.001).Whole‐brain voxel‐wise analyses revealed differential cortical thinning in MCI groups VS controls, with prodromal AD having more extensive atrophy, especially in the MTL (Figure 4). Mismatch MCI had lower mean anterior‐to‐posterior hippocampal volume ratio (p=0.016). While baseline entorhinal cortex, BA35, BA36, and parahippocampal cortex volumes were comparable (both groups had significant atrophy compared to controls), mismatch MCI had slower atrophy in these regions and the hippocampus (Table 2). Conclusion Mismatch MCI’s lower anterior‐to‐posterior hippocampal volume suggests possible enrichment in individuals with TDP‐43, a common non‐AD pathology, given previous work suggesting TDP‐43 preferentially affects the anterior hippocampus. Overall, these results support the concept that mismatch MCI and prodromal AD have different underlying pathologic profiles in light of their divergent cognition and neurodegenerative topography.