Gradual Disturbances of the Amplitude of Low-Frequency Fluctuations (ALFF) and Fractional ALFF in Alzheimer Spectrum

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.

Depression Affects Intrinsic Brain Activity in Patients With Mild Cognitive Impairment

“…The robustness of the results was tested to prove the regions we found was stability and repeatability ( Supplementary Figures S2, S3). In the studies pretend to explore the neural mechanism about MCI, AD or depression, these regions also have been mentioned (Langenecker et al, 2007; Alexopoulos et al, 2008;Yao et al, 2009;Lee et al, 2012;Xie et al, 2012;Zhang et al, 2012;Rizio and Dennis, 2014;Guo et al, 2016;Stoyanov et al, 2017;Kandilarova et al, 2018;Yang et al, 2018;Kandilarova et al, 2019). These brain regions may be the proof of a possible shared pathophysiology in both depression and MCI (Yao et al, 2009;Zhang et al, 2012).…”

“…IBA involves dynamic neural and metabolic activities, it is activity and plays a pivotal role in brain function (Dai and He, 2014;Raichle, 2015). These methods have been widely used to evaluate the IBA of neurological disorders or neuropsychiatric disorders, such as AD, depression, and MCI (Yao et al, 2009;Zhang et al, 2012;Guo et al, 2016;Wee et al, 2016;Stoyanov et al, 2017;Zhang et al, 2017;Kandilarova et al, 2018;Yang et al, 2018;Liu et al, 2019). Furthermore, evidence indicated that once brain got an internal or external stimuli, it could respond by dynamic integration or adjustment over multiple time scales (Hutchison et al, 2013;Bassett and Sporns, 2017;Yan et al, 2017).…”

“…Studies have identified regions in MCI compared with the NC, with a decreased or increased ALFF/fALFF/ReHo (Han et al, 2011;Zhang et al, 2012;Dai and He, 2014;Liu et al, 2018Liu et al, , 2019Yang et al, 2018). Previous study found that changes from ALFF/fALFF measurements of IBA may be worthwhile to characterize the early and gradual changes in physiological alterations throughout AD progression (Yang et al, 2018). Moreover, in MCID group the FC density values were higher in the left MTG than those in the MCI without depression patients (MCIND) (Liu et al, 2018).…”

Altered Patterns of Phase Position Connectivity in Default Mode Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

“…In previous studies, aMCI group showed more widespread topological changes involving the frontal lobes (Barban et al, 2017), and aberrant connectivity was also found in patients with SCD between DMN and FG due to cognitive impairment (Xue et al, 2019). Besides, an increasing trend of values of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF were detected in FG (Yang et al, 2018). Therefore, changes in FG may be related to cognitive dysfunction.…”

“…Anatomically, it includes the anterior DMN (aDMN) which is primarily composed of the ventromedial prefrontal cortex (vmPFC), and posterior DMN (pDMN) which mainly focuses on the posterior cingulate cortex (PCC) (Xu et al, 2016). Notice that the former mainly concerns memory extinction and self-referential mental idealization, while the latter is closely related to the function of episodic memory retrieval (Yang et al, 2017(Yang et al, , 2018. Previously, it has been reported that amyloid deposits are detected with a great probability in the PCC which served as a primary part of DMN (Wang et al, 2013).…”