DTI can be used to assess the degradation of WM tracts by measuring the FA and MD. Decreased FA/increased MD values in the AD hippocampus have been reported by many studies. In contrast, only a few studies reported on hydrocephalus by using the DTI technique. In elderly patients with dementia and with dilated ventricles, it is often difficult to differentiate iNPH from AD with visual measurements on MR imaging. The aim of this study was to investigate the changes of microstructural integrity of the hippocampus in iNPH by using DTI and determining whether this method could be a new diagnostic tool to differentiate iNPH from AD. We recruited 43 participants (15 healthy controls, 15 patients with AD, and 13 patients with iNPH). The FA and MD values were measured by using the region-of-interest method in the hippocampal head, body, and tail on both sides. Clinical history, neurologic examination, and neuropsychological assessment were included. The FA values were the lowest in the patients with AD, the patients with iNPH, and the healthy controls in this order. The MD values were the highest in the same order. These findings were consistent in the 3 subdivisions of the bilateral hippocampal regions. Hippocampal volume was not different between patients with iNPH and AD. The microstructural alterations of the hippocampus were more sensitive than the volumetric changes in AD and iNPH. DTI analysis might be a useful tool for discriminating AD from iNPH.

Hong YJ, et al. J Korean Med Sci. 2015 Nov;30(11):1652-1658. https://doi.org/10.3346/jkms.2015.30.11.1652

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.

High-dose donepezil is currently prescribed for patients with Alzheimer’s disease (AD) who showed poor or waning response to a lower dose at the risk of increasing cholinergic side effects. However, the adverse events (AEs) depending on the method of dose escalation have not been clarified yet. This study aimed to find out whether dose titration before escalating to donepezil 23 mg is preferred. We investigated safety and tolerability of donepezil 23 mg during the first 12 weeks of dose escalation in patients with moderate to severe AD. This study was a 12-week, multicenter, randomized, open-label prospective trial. We included patients with moderate to severe AD who were treated with a stable dose of donepezil 10 mg/day. Patients were randomized into 3 groups according to the dose escalation method: 15 mg of donepezil for 4 weeks before escalating to 23 mg (group 1), 10 mg and 23 mg on alternate days for 4 weeks prior to escalation (group 2), and direct escalation to 23 mg (group 3). Safety analyses included incidence, severity, timing of AEs, relationship to the study drug, and premature study discontinuation due to AEs between the groups. Among 175 enrolled, 110 patients completed the study. Baseline characteristics were similar among the groups. Using safety population (N = 160), cholinergic gastrointestinal symptoms including anorexia and nausea were the most common AEs and titration groups showed significantly fewer cases of nausea as compared with those in no-titration group. In this study, dose titration before escalating to donepezil 23 mg/day showed better safety in terms of cholinergic AEs. We suggest that dose titration during the first 4 weeks can be recommended for patients with moderate to severe AD. Clinicaltrials.gov , NCT02550665. Retrospectively registered on 15 Sep 2015.