Abstract
Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.
Highlights
The pathophysiological process of Alzheimer’s disease (AD) is believed to begin years before clinical symptoms become apparent[1]
Subjective memory decline (SMD) individuals were comparable to the healthy controls with respect to all the demographic and clinical variables
MANOVA clearly showed a gradual increase in cognitive impairment according to more advanced disease stages (F(42, 540) = 6.149; p < 0.001; AD >mild cognitive impairment (MCI) >SMD >healthy controls)
Summary
The pathophysiological process of Alzheimer’s disease (AD) is believed to begin years before clinical symptoms become apparent[1]. Studying patterns of atrophy instead of single regions of interest has yielded higher diagnostic performance[16] These patterns of atrophy can be captured with multivariate data analysis methods such as Orthogonal Projection to Latent Structures (OPLS)[22]. The disease severity index describes if an individual has an AD-like pattern of brain atrophy or a healthy control-like (HC-like) pattern of brain atrophy. To our knowledge, this method has not been applied to SMD individuals yet. We hypothesized that SMD with an AD-like pattern of brain atrophy would have worse cognitive performance at baseline, increased neocortical amyloid burden, higher frequency of the APOE ε 4 allele, and higher rate of progression to MCI or dementia
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