Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies

Abstract

Background: Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria.

Objectives: The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease-Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD.

Design: Prospective cohort study.

Setting and participants: SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose-positron emission tomography (FDG-PET) were enrolled from the USA.

Methods: Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed.

Results: SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters.

Conclusions: Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients.

Figure 1

3D-SSP analyses of baseline fluorodeoxyglucose–positron emission tomography in Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) (A) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (B). These are the results of group comparison between MCI patients and normal controls (NC). MCI patients showed a significant decrease of the cerebral metabolic rate for glucose (CMRgl) not only in the regions preferentially affected by Alzheimer's disease (including the inferior parietal lobules and precuneus) but also in the frontal lobules. Colour bar indicates the mean Z score of CMRgl. LAT, lateral view; SUP, superior view; INF, inferior view; ANT, anterior view; POST, posterior view; MED, medial view; GLB, reference region in global brain; CLB, reference region in cerebellum.

Figure 2

3D-SSP analyses of baseline fluorodeoxyglucose–positron emission tomography in Studies on Diagnosis of Early Alzheimer's Disease—Japan. These are the results of group comparisons between Alzheimer's disease (AD) converters and non-converters. AD converters show a greater reduction in glucose metabolism for AD-associated and frontal regions. This hypometabolism was more evident in the converters within 1 year after inclusion compared with the converters from 1 year to 2 years after inclusion. (A) AD converters within 1 year after inclusion and non-converters. (B) AD converters from 1 year to 2 years after inclusion and non-converters.

Figure 3

Statistical parametric mapping of the brain regions correlated with baseline profiles in Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI). The regions displayed in red indicate significant regional hypometabolism (p<0.05). (A) Correlation between lower Mini-Mental Status Examination (MMSE) scores and glucose metabolism. (B) Correlation between lower Logical Memory subset of the Wechsler Memory Scale Revised (WMS-R LM) scores and glucose metabolism.

Figure 4

Statistical parametric mapping of the brain regions correlated with baseline profiles in Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI). The regions displayed in red indicate significant regional hypometabolism (p<0.05). (A) Inverse correlation between Geriatric Depression Scale (GDS) scores and glucose metabolism. (B) Inverse correlation between age and glucose metabolism.