Abstract
Background: Alzheimer’s disease (AD) is a common neurodegenerative disease in which the brain undergoes alterations for decades before symptoms become obvious. Subjective cognitive decline (SCD) have self-complain of persistent decline in cognitive function especially in memory but perform normally on standard neuropsychological tests. SCD with the presence of AD pathology is the transitional stage 2 of Alzheimer’s continuum, earlier than the prodromal stage, mild cognitive impairment (MCI), which seems to be the best target to research AD. In this study, we aimed to detect the transformational patterns of the intrinsic brain activity as the disease burden got heavy.Method: In this study, we enrolled 44 SCD, 55 amnestic MCI (aMCI), 47 AD dementia (d-AD) patients and 57 normal controls (NC) in total. A machine learning classification was utilized to detect identification accuracies between groups by using ALFF, fALFF, and fusing ALFF with fALFF features. Then, we measured the amplitude of the low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) levels in three frequency bands (classic: 0.01–0.1 Hz; slow-5: 0.01–0.027 Hz; and slow-4: 0.027–0.073 Hz) and compared alterations in patients with NC.Results: In the machine learning verification, the identification accuracy of SCD, aMCI, d-AD from NC was higher when fused ALFF and fALFF features (76.44, 81.94, and 91.83%, respectively) than only using ALFF or fALFF features. Several brain regions showed significant differences in ALFF/fALFF within these bands among four groups: brain regions presented decreasing trend of values, including the Cingulum_Mid_R (aal), bilateral inferior cerebellum lobe, bilateral precuneus, and the Cingulum_Ant_R (aal); increasing trend of values were detected in the Hippocampus_L (aal), Frontal_Mid_Orb_R (aal), Frontal_Sup_R (aal) and Paracentral_Lobule_R (aal) as disease progressed. The normalized ALFF/fALFF values of these features were significantly correlated with the neuropsychological test scores.Conclusion: This study revealed gradual disturbances in intrinsic brain activity as the disease progressed: the normal objective performance in SCD may be dependent on compensation; as disease advanced, the cognitive function gradually impaired and decompensated in aMCI, severer in d-AD. Our results indicated that the ALFF and fALFF may help detect the underlying pathological mechanism in AD continuum.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02353884 and NCT02225964.
Highlights
Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease of the elderly without a definite pathogenesis or effective treatment being found to decelerate the progression of this disorder, leading to poor outcomes and severe burdens to both the family and society (Scheltens et al, 2016)
All subjects underwent a set of standardized clinical evaluations, including a medical history enquiry, neurological examination, and a suite of neuropsychological tests, which included the Chinese version of the Mini–Mental State Examination (MMSE), the Beijing version of Montreal Cognitive Assessment (MoCA) (Lu et al, 2011), the auditory verbal learning test (AVLT) (Guo et al, 2007), Clinical Dementia Rating Scale (CDR) (Morris, 1993), Activity of Daily Living (ADL), Hachinski Ischemic Scale (HIS), Hamilton depression rating scale (HAMD) (Hamilton, 1960), and Center for Epidemiologic Studies depression scale (Dozeman et al, 2011)
The amnestic mild cognitive impairment (MCI) (aMCI) subjects were included based on the following items: (a) with or without self-perceived memory complaint and with informant complaints; (b) objectively impaired memory confirmed by MMSE (≤19 for illiteracy, ≤22 for 1–6 educational years, ≤26 for more than 6 educational years) and MoCA scores (≤13 for illiteracy, ≤19 for 1–6 educational years, ≤24 for more than 6 educational years); (c) clear-cut history of worsening cognition; (d) failure to meet the criteria for dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, revised (DSM-IV-R); and (e) CDR score of 0.5
Summary
Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease of the elderly without a definite pathogenesis or effective treatment being found to decelerate the progression of this disorder, leading to poor outcomes and severe burdens to both the family and society (Scheltens et al, 2016). SCD refers to those elderly people who self-report a persistent decline in cognition but perform normally on the standard assessment with a higher conversion risk to MCI or d-AD, which is the transitional stage 2 of Alzheimer’s continuum in the presence of AD pathology and seems to be the best target to research the underlying mechanism of AD (Sperling et al, 2011; Jessen et al, 2014; Mitchell et al, 2014; Jack et al, 2018; Jessen and Rodriguez Nee 2018). We aimed to detect the transformational patterns of the intrinsic brain activity as the disease burden got heavy
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