Brain controllability distinctiveness between depression and cognitive impairment

Alzheimer's disease (AD) is a progressive form of dementia marked by cognitive and memory deficits, estimated to affect ∼5.7 million Americans and account for ∼$277 billion in medical costs in 2018. Depression is one of the most common neuropsychiatric disorders that accompanies AD, appearing in up to 50% of patients. AD and Depression commonly occur together with overlapped symptoms (depressed mood, anxiety, apathy, and cognitive deficits.) and pose diagnostic challenges early in the clinical presentation. Understanding their relationship is critical for advancing treatment strategies, but the interaction remains poorly studied and thus often leads to a rapid decline in functioning. Modern systems and control theory offer a wealth of novel methods and concepts to assess the important property of a complex control system, such as the brain. In particular, the brain controllability analysis captures the ability to guide the brain behavior from an initial state (healthy or diseased) to a desired state in finite time, with suitable choice of inputs such as external or internal stimuli. The controllability property of the brain's dynamic processes will advance our understanding of the emergence and progression of brain diseases and thus helpful in the early diagnosis and novel treatment approaches. This study aims to assess the brain controllability differences between mild cognitive impairment (MCI), as prodromal AD, and Depression. This study used diffusion tensor imaging (DTI) data from 60 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 15 cognitively normal subjects and 45 patients with MCI, including 15 early MCI (EMCI) patients without depression, 15 EMCI patients with mild depression (EMCID), and 15 late MCI (LMCI) patients without depression. The structural brain network was firstly constructed and the brain controllability was characterized for each participant. The controllability of default mode network (DMN) and its sub-regions were then compared across groups in a structural basis. Results indicated that the brain average controllability of DMN in EMCI, LMCI, and EMCID were significantly decreased compared to healthy subjects (P < 0.05). The EMCI and LMCI groups also showed significantly greater average controllability of DMN versus the EMCID group. Furthermore, compared to healthy subjects, the regional controllability of the left/right superior prefrontal cortex and the left/right cingulate gyrus in the EMCID group showed a significant decrease (P < 0.01). Among these regions, the left superior prefrontal region's controllability was significantly decreased (P < 0.05) in the EMCID group compared with EMCI and LMCI groups. Our results provide a new perspective in understanding depressive symptoms in MCI patients and provide potential biomarkers for diagnosing depression from MCI and AD.