PMID- 30121086 OWN - NLM STAT- MEDLINE DCOM- 20190806 LR - 20190806 IS - 1758-9193 (Electronic) VI - 10 IP - 1 DP - 2018 Aug 18 TI - Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer's disease. PG - 82 LID - 10.1186/s13195-018-0413-8 [doi] LID - 82 AB - BACKGROUND: Patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach. METHODS: We examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains. RESULTS: We demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition. CONCLUSIONS: We demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment. FAU - Vipin, Ashwati AU - Vipin A AD - Centre for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. FAU - Loke, Yng Miin AU - Loke YM AD - Centre for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. FAU - Liu, Siwei AU - Liu S AD - Centre for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. FAU - Hilal, Saima AU - Hilal S AD - Department of Pharmacology, Clinical Research Centre, National University Health System, National University of Singapore, Singapore, Singapore. AD - Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore. FAU - Shim, Hee Youn AU - Shim HY AD - Centre for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. FAU - Xu, Xin AU - Xu X AD - Department of Pharmacology, Clinical Research Centre, National University Health System, National University of Singapore, Singapore, Singapore. AD - Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore. FAU - Tan, Boon Yeow AU - Tan BY AD - St. Luke's Hospital, Singapore, Singapore. FAU - Venketasubramanian, Narayanaswamy AU - Venketasubramanian N AD - Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore. FAU - Chen, Christopher Li-Hsian AU - Chen CL AD - Department of Pharmacology, Clinical Research Centre, National University Health System, National University of Singapore, Singapore, Singapore. AD - Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore. FAU - Zhou, Juan AU - Zhou J AUID- ORCID: 0000-0002-0180-8648 AD - Centre for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. helen.zhou@duke-nus.edu.sg. AD - Clinical Imaging Research Centre, The Agency for Science, Technology and Research and National University of Singapore, Singapore, Singapore. helen.zhou@duke-nus.edu.sg. LA - eng GR - NMRC/CG/013/2013/National Medical Research Council (SG)/International GR - NMRC/CG/NUHS/2010/National Medical Research Council/International GR - NMRC/CIRG/1390/2014/National Medical Research Council/International GR - BMRC 04/1/36/372/Biomedical Research Council Singapore/International GR - Duke-NUS Medical School Signature Research Program/Ministry of Health -Singapore (SG)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180818 PL - England TA - Alzheimers Res Ther JT - Alzheimer's research & therapy JID - 101511643 RN - S88TT14065 (Oxygen) MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/*complications/diagnostic imaging MH - Brain/diagnostic imaging/*physiopathology MH - Brain Mapping MH - Cerebrovascular Disorders/*complications MH - Chi-Square Distribution MH - Cognitive Dysfunction/*complications/*diagnostic imaging MH - Female MH - Humans MH - Image Processing, Computer-Assisted MH - Magnetic Resonance Imaging MH - Male MH - Mental Status Schedule MH - Middle Aged MH - Models, Neurological MH - Neural Pathways/diagnostic imaging/*physiopathology MH - Neuropsychological Tests MH - Oxygen/blood PMC - PMC6098837 OTO - NOTNLM OT - Alzheimer's disease OT - Cerebrovascular disease OT - Diffusion tensor imaging OT - Functional connectivity OT - Network OT - Neurodegeneration OT - Structural connectivity COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was conducted in accordance with the Declaration of Helsinki, and written informed consent was obtained from both the patients and the patients' caregivers. Ethics approval was granted by the National Healthcare Group Review Board of Singapore (NUHS1288/2010). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/08/20 06:00 MHDA- 2019/08/07 06:00 PMCR- 2018/08/18 CRDT- 2018/08/20 06:00 PHST- 2018/03/21 00:00 [received] PHST- 2018/07/23 00:00 [accepted] PHST- 2018/08/20 06:00 [entrez] PHST- 2018/08/20 06:00 [pubmed] PHST- 2019/08/07 06:00 [medline] PHST- 2018/08/18 00:00 [pmc-release] AID - 10.1186/s13195-018-0413-8 [pii] AID - 413 [pii] AID - 10.1186/s13195-018-0413-8 [doi] PST - epublish SO - Alzheimers Res Ther. 2018 Aug 18;10(1):82. doi: 10.1186/s13195-018-0413-8.