Abstract
BackgroundAlthough amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer’s disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by clinical dementia rating sum of boxes (CDR-SOB). Then, we compared the clinical and neuroimaging features among groups classified by cognitive trajectory.MethodsWe retrospectively recruited 278 patients with aMCI who underwent three or more timepoints of neuropsychological testing. They also had magnetic resonance imaging (MRI) including structured three-dimensional volume images. Cortical thickness was measured using surface-based methods. We performed trajectory analyses to classify our aMCI patients according to their progression and investigate their cognitive trajectory using CDR-SOB.ResultsTrajectory analyses showed that patients with aMCI were divided into three groups: stable (61.8%), slow decliner (31.7%), and fast decliner (6.5%). Changes throughout a mean follow-up duration of 3.7 years in the CDR-SOB for the subgroups of stable/slow/fast decliners were 1.3-, 6.4-, and 12-point increases, respectively. Decliners were older and carried apolipoprotein E4 (APOE4) genotypes more frequently than stable patients. Compared with the stable group, decliners showed a higher frequency of aMCI patients with both visual and verbal memory dysfunction, late stage aMCI, and multiple domain dysfunction. In addition, compared with the stable group, the slow decliners showed cortical thinning predominantly in bilateral parietotemporal areas, while the fast decliners showed cortical thinning predominantly in bilateral frontotemporal areas. Both decliner groups showed worse cognitive function in attention, language, visuospatial, memory, and frontal/executive domains than the stable group.ConclusionsOur data-driven trajectory analysis provides new insights into heterogeneous cognitive trajectories of aMCI and further suggests that baseline clinical and neuroimaging profiles might predict aMCI patients with poor prognosis.
Highlights
Amnestic mild cognitive impairment is generally considered to be a prodromal stage of Alzheimer’s disease, patients with amnestic mild cognitive impairment (aMCI) show heterogeneous patterns of progression
These studies have shown that aMCI is more likely to progress in patients with brain atrophy, with evidence of amyloid deposition (measured using positron emission tomography (PET)), and carriage of the apolipoprotein E4 (APOE4) allele [7, 8]
Previous studies from our group showed that the progression of aMCI to dementia depended on the modality and severity of involved memory dysfunction, and the multiplicity of impaired cognitive domains [9,10,11,12,13]
Summary
Amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer’s disease, patients with aMCI show heterogeneous patterns of progression. Previous studies from our group showed that the progression of aMCI to dementia depended on the modality and severity of involved memory dysfunction, and the multiplicity of impaired cognitive domains [9,10,11,12,13]. These studies were based on hypothesis-driven analysis, that is researchers classified participants into several subgroups according to their hypothesis. A recent study from our group suggested that trajectory analysis is useful to identify prognostic profiles in patients with non-amnestic MCI [15]
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