Clinical and cognitive characteristics of preclinical Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative cohort

Ryoko Ihara; Atsushi Iwata; Kazushi Suzuki; Takeshi Ikeuchi; Ryozo Kuwano; Takeshi Iwatsubo; Japanese Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.trci.2018.10.004

Clinical and cognitive characteristics of preclinical Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative cohort

Alzheimers Dement (N Y). 2018 Nov 26:4:645-651. doi: 10.1016/j.trci.2018.10.004. eCollection 2018.

Authors

Ryoko Ihara^{1

2}, Atsushi Iwata³, Kazushi Suzuki¹, Takeshi Ikeuchi⁴, Ryozo Kuwano⁴, Takeshi Iwatsubo^{1

5}; Japanese Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan.
² Department of Innovative Dementia Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan.
⁴ Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
⁵ Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Abstract

Introduction: The objective of this study was to determine the frequency and clinical and cognitive characteristics of preclinical Alzheimer's disease (AD) in a Japanese population to effectively design and conduct future preventive trials on preclinical AD.

Methods: Three-year longitudinal data from cognitively normal participants who underwent cerebrospinal fluid biomarker measurement and/or amyloid positron emission tomography in the Japanese Alzheimer's Disease Neuroimaging Initiative, were analyzed. Comparisons between participants with and without amyloid β (Aβ) accumulation, and between those with and without elevated tau levels tau among participants with Aβ accumulation were performed.

Results: Among 84 participants with available cerebrospinal fluid biomarker and/or amyloid positron emission tomography data, 19 (22.6%) exhibited Aβ accumulation. The frequency of APOE ε4 alleles was significantly higher in participants with Aβ accumulation. There were no significant differences in any of the cognitive tests at the baseline; however, participants with Aβ accumulation exhibited a decline in clock drawing test (linear mixed-effects model, P = .008) and a tendency toward loss of practice effects in the Mini-Mental State Examination and the logical memory over time. Although it did not reach statistical significance, the analysis indicated a decline in measurements of executive function over time in participants with elevated tau levels compared with those with normal tau levels.

Discussion: The frequency of preclinical AD in the Japanese Alzheimer's Disease Neuroimaging Initiative was lower than in similar studies because of the younger age of the participants and lower frequency of APOE ε4 carriage. Although limitations in sample size precluded definitive conclusions, the results suggest that even in the preclinical phase of AD, loss of practice effects in episodic memory tests and at a later stage, decline in executive function, are present. These findings may be useful for recruitment of individuals with preclinical AD and establishing a novel cognitive composite for use in clinical trials on preclinical AD.

Keywords: APOE; Episodic memory; Executive function; J-ADNI; Practice effect; Preclinical Alzheimer's disease.