- Inglese, Marianna;
- Patel, Neva;
- Linton-Reid, Kristofer;
- Loreto, Flavia;
- Win, Zarni;
- Perry, Richard J;
- Carswell, Christopher;
- Grech-Sollars, Matthew;
- Crum, William R;
- Lu, Haonan;
- Malhotra, Paresh A;
- Aboagye, Eric O
Background
Alzheimer's disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care.Methods
We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called "Alzheimer's Predictive Vector" (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO).Results
The ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer's related pathologies (98% and 81% accuracy between ADrp - including the early form, mild cognitive impairment - and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype.Conclusions
This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.