Hippocampal volumes predict risk of dementia with lewy bodies in mild cognitive impairment


      Amnestic mild cognitive impairment (MCI) has been established on clinical grounds in order to identify individuals with prodromal Alzheimer’s disease (AD) dementia. However, patients with MCI, who have impairments non-amnestic cognitive domains, may be at an increased risk of dementia with Lewy bodies (DLB). We investigated whether the risk of AD dementia versus DLB can be predicted by hippocampal volume (HV) in patients with MCI, broadly defined with impairments in amnestic and/or non-amnestic cognitive domains.


      Consecutive patients with MCI (n=108) from the Mayo Clinic Alzheimer’s Disease Research Center, who participated in the MRI study during years 2005 through 2013 were included and followed with approximately annual clinical evaluations. Patients with neurologic diseases other than cognitive impairment were excluded. MRIs were performed at 3Tesla and 3D MPRAGE scans were acquired at baseline. HVs were analyzed using FreeSurfer (5.3), and adjusted for TIV. Hippocampal atrophy was determined from the 10th percentile of the measurement distributions in clinically diagnosed AD patients in a previous study. The hazard ratios for progression to AD dementia versus DLB were estimated by taking into account the competing risks.


      After a median (range) follow-up of 1.97 (0.78-8.10) years, 18 (16%) patients with MCI progressed to probable DLB and 34 (32%) progressed to AD dementia. Taking into account the competing risks, the estimated hazard ratio (95% confidence interval) for hippocampal atrophy (relative to normal HV) for progression to AD dementia was 4.58 (2.28-9.19) (p<0.001). The estimated hazard ratio for hippocampal atrophy (relative to normal HV) for progression to DLB was 0.213 (0.050-0.912), corresponding to an estimated hazard ratio for normal HV (relative to hippocampal atrophy) for progression to DLB of 4.71 (1.1-20.2) (p=0.037). (Figure)


      Patients with MCI who progress to DLB tend to have normal HV. Whereas hippocampal atrophy increases the risk of progression to AD dementia, preserved hippocampal volumes increases the risk of DLB in MCI. Preservation of HV may be a supportive feature of prodromal DLB in patients with MCI.
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