Effect of donepezil in Alzheimer disease can be measured by a computerized human analog of the Morris water maze.

BACKGROUND: Drug development for Alzheimer disease (AD) is challenged by the success in animal models tested in the Morris water maze (MWM) and the subsequent failures to meet primary outcome measures in phase II or III clinical trials in patients. The human variant of MWM (hMWM) enables us to examine allocentric and egocentric navigation as in the MWM. OBJECTIVE: It was the aim of this study to examine the utility of a computerized hMWM to assess the effects of donepezil in mild AD. METHODS: Donepezil 5 mg/day was started after initial hMWM testing in the treated group (n = 12), and after 28 days, the dose was increased to 10 mg/day. The performance after 3 months was compared to that of a non-treated group (n = 12). RESULTS: Donepezil stabilized or improved the spatial navigation performance after 3 months, especially in the allocentric delayed recall subtask (p = 0.014). CONCLUSIONS: The computerized hMWM has the potential to measure the effects of donepezil in mild AD. It is a sensitive cognitive outcome measure in AD clinical trials.

From Morris Water Maze to computer tests in the prediction of Alzheimer's disease.

BACKGROUND: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD). OBJECTIVE: Contrast results from computer versus real-space versions of the HGT. METHODS: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. RESULTS: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. CONCLUSIONS: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

SIMULTANEOUS BILATERAL ACUTE ANGLE-CLOSURE GLAUCOMA IN MILLER FISHER SYNDROME.

PURPOSE: To report a case of patient with Miller Fisher syndrome, complicated by simultaneous bilateral acute angle-closure glaucoma in her slightly (+1.5) hyperopic eyes. METHODS: We present a case report of a 71-year-old female patient presenting with total ophthalmoplegia, areflexia, ataxia and bilateral acute angle-closure glaucoma. RESULTS: The initial ocular examination revealed hand motion in the both eyes and oedematic corneas. Initial intraocular pressure was immeasurable high (measurment by Tonopen Avia). Measurement was possible after intravenous Mannitol 20 % infusion on both eyes as 54 and 56 mm Hg, respectively. Local medical therapy of pilocarpine, timolol, dorsolamide and dexamethasone improve intraocular pressure into normal limits within several hours. Prophylactic peripheral Nd-YAG laser iridotomy was performed on a both eyes two days later. Systemic treatment involved plasma exchange and rehabilitation program. Subsequent cataract surgery on both eyes with posterior capsule lens implantation improve the best corrected visual acuity on right eye from 0.5 to 1.0 and the left eye from 0.5 to 0.8, respectively. Intraocular pressure is within normal limits without any glaucoma therapy. Follow up period is three years. CONCLUSIONS: This is the second reported case of patient with Miller Fisher syndrome and simultaneous bilateral acute angle-closure glaucoma and the fifth reported case of Miller Fisher syndrome and acute angle-closure glaucoma. Treatment for both conditions made a very good recovery.

Real-space path integration is impaired in Alzheimer's disease and mild cognitive impairment.

INTRODUCTION: Path integration (PI) is an important component of spatial navigation that integrates self-motion cues to allow the subject to return to a starting point. PI depends on the structures affected early in the course of Alzheimer's disease (AD) such as the medial temporal lobe and the parietal cortex. OBJECTIVES: To assess whether PI is impaired in patients with mild AD and amnestic mild cognitive impairment (aMCI) and to investigate the role of the hippocampus, entorhinal and inferior parietal cortex in this association. METHODS: 27 patients with aMCI, 14 with mild AD and 18 controls completed eight trials of Arena Path Integration Task. The task required subjects with a mask covering their eyes to follow an enclosed triangle pathway through two previously seen places: start-place1-place2-start. Brains were scanned at 1.5T MRI and respective volumes and thicknesses were derived using FreeSurfer algorithm. RESULTS: Controlling for age, education, gender and Mini-Mental State Examination score the aMCI and AD subjects were impaired in PI accuracy on the pathway endpoint (p=0.042 and p=0.013) compared to controls. Hippocampal volume and thickness of entorhinal and parietal cortices explained separately 36-45% of the differences in PI accuracy between controls and aMCI and 28-31% of the differences between controls and AD subjects. CONCLUSIONS: PI is affected in aMCI and AD, possibly as a function of neurodegeneration in the medial temporal lobe structures and the parietal cortex. PI assessment (as a part of spatial navigation testing) may be useful for identification of patients with incipient AD.