TY - JOUR
T1 - Brain controllability distinctiveness between depression and cognitive impairment
AU - Fang, Feng
AU - Gao, Yunyuan
AU - Schulz, Paul E.
AU - Selvaraj, Sudhakar
AU - Zhang, Yingchun
N1 - Funding Information:
The research is supported in part by the University of Houston. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co. Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Funding Information:
The research is supported in part by the University of Houston. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Publisher Copyright:
© 2021
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Brain controllability
KW - Cognitive impairment
KW - Depression
KW - Diffusion tensor imaging
KW - Structural network
KW - Brain/diagnostic imaging
KW - Magnetic Resonance Imaging
KW - Humans
KW - Alzheimer Disease/diagnostic imaging
KW - Cognitive Dysfunction/diagnostic imaging
KW - Diffusion Tensor Imaging
UR - http://www.scopus.com/inward/record.url?scp=85111899202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111899202&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2021.07.106
DO - 10.1016/j.jad.2021.07.106
M3 - Article
C2 - 34375212
AN - SCOPUS:85111899202
SN - 0165-0327
VL - 294
SP - 847
EP - 856
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -