Journal
THERANOSTICS
Volume 8, Issue 12, Pages 3237-3255Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.23772
Keywords
subjective cognitive decline; Alzheimer's disease; DTI; rich club; graph theory
Categories
Funding
- National Key Research and Development Program of China [2017YFB1002504]
- National Natural Science Foundation of China [81671776, 61633018, 61727807]
- Beijing Municipal Science & Technology Commission [Z131100006813022, PXM2017_026283_000002]
- Beijing Nova Program [Z171100001117057]
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Alzheimer's disease (AD) has a preclinical phase that can last for decades prior to clinical dementia onset. Subjective cognitive decline (SCD) is regarded as the last preclinical AD stage prior to the development of amnestic mild cognitive decline (aMCI) and AD dementia (d-AD). The analysis of brain structural networks based on diffusion tensor imaging (DTI) has identified the so-called 'rich club', a set of cortical regions highly connected to each other, with other regions referred to as peripheral. It has been reported that rich club architecture is affected by regional atrophy and connectivity, which are reduced in patients with aMCI and d-AD. Methods: We recruited 62 normal controls, 47 SCD patients, 60 aMCI patients and 55 d-AD patients and collected DTI data to analyze rich-club organization. Results: We demonstrated that rich club organization was disrupted, with reduced structural connectivity among rich club nodes, in aMCI and d-AD patients but remained stable in SCD patients. In addition, SCD, aMCI and d-AD patients showed similar patterns of disrupted peripheral regions and reduced connectivity involving these regions, suggesting that peripheral regions might contribute to cognitive decline and that disruptions here could be regarded as an early marker of SCD. This organization could provide the fundamental structural architecture for complex cognitive functions and explain the low prevalence of cognitive problems in SCD patients. Conclusions: These findings reveal a disrupted pattern of the AD connectome that starts in peripheral regions and then hierarchically propagates to rich club regions, when patients show clinical symptoms. This pattern provides evidence that disruptions in rich club organization are a key factor in the progression of AD that can dynamically reflect the progression of AD, thus representing a potential biomarker for early diagnosis.
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