Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial

Nick W. Bray; Frederico Pieruccini-Faria; Suzanne T. Witt; Kenneth Rockwood; Robert Bartha; Timothy J. Doherty; Lindsay S. Nagamatsu; Quincy J. Almeida; Teresa Liu-Ambrose; Laura E. Middleton; Louis Bherer; Manuel Montero-Odasso

doi:10.1007/s11357-022-00702-4

Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial

Nick W. Bray, Frederico Pieruccini-Faria, Suzanne T. Witt, Kenneth Rockwood, Robert Bartha, Timothy J. Doherty, Lindsay S. Nagamatsu, Quincy J. Almeida, Teresa Liu-Ambrose, Laura E. Middleton, Louis Bherer, Manuel Montero-Odasso

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11 Citas (Scopus)

Resumen

Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson’s correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676

Idioma original	English
Publicación	GeroScience
DOI	https://doi.org/10.1007/s11357-022-00702-4
Estado	Accepted/In press - 2022

Nota bibliográfica

Funding Information:
The SYNERGIC Trial is funded by Canadian Consortium on Neurodegeneration in Aging (CCNA Grant# “FRN” CNA 137794). The CCNA is supported by a grant from the Canadian Institutes of Health Research with funding from several partners. Dr Nick W. Bray was supported by a 2018–2021 Ontario Graduate Scholarship (OGS); the “Fellowship in Care of the Older Adult” from the St. Joseph’s Healthcare Foundation, Parkwood Institute, Division of Geriatric Medicine, University of Western Ontario; and the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794). Teresa Liu-Ambrose is a Canada Research Chair (Tier I) in Healthy Aging. Dr. Montero-Odasso’s program in Gait and Brain Health is supported by grants from the Canadian Institute of Health Research (MOP 211220; PJT 153100), the Ontario Ministry of Research and Innovation (ER11–08–101), the Ontario Neurodegenerative Diseases Research Initiative (OBI 34739), the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794), and Department of Medicine Program of Experimental Medicine Research Award (POEM 768915), University of Western Ontario. He is the first recipient of the Schulich Clinician-Scientist Award.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Aging Association.

ASJC Scopus Subject Areas

Ageing
veterinary (miscalleneous)
Complementary and alternative medicine
Geriatrics and Gerontology
Cardiology and Cardiovascular Medicine

PubMed: MeSH publication types

Journal Article

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10.1007/s11357-022-00702-4

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Bray, N. W., Pieruccini-Faria, F., Witt, S. T., Rockwood, K., Bartha, R., Doherty, T. J., Nagamatsu, L. S., Almeida, Q. J., Liu-Ambrose, T., Middleton, L. E., Bherer, L., & Montero-Odasso, M. (Aceptado/En prensa). Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial. GeroScience. https://doi.org/10.1007/s11357-022-00702-4

Bray, NW, Pieruccini-Faria, F, Witt, ST, Rockwood, K, Bartha, R, Doherty, TJ, Nagamatsu, LS, Almeida, QJ, Liu-Ambrose, T, Middleton, LE, Bherer, L & Montero-Odasso, M 2022, 'Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial', GeroScience. https://doi.org/10.1007/s11357-022-00702-4

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title = "Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial",

abstract = "Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson{\textquoteright}s correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676",

author = "Bray, {Nick W.} and Frederico Pieruccini-Faria and Witt, {Suzanne T.} and Kenneth Rockwood and Robert Bartha and Doherty, {Timothy J.} and Nagamatsu, {Lindsay S.} and Almeida, {Quincy J.} and Teresa Liu-Ambrose and Middleton, {Laura E.} and Louis Bherer and Manuel Montero-Odasso",

note = "Funding Information: The SYNERGIC Trial is funded by Canadian Consortium on Neurodegeneration in Aging (CCNA Grant# “FRN” CNA 137794). The CCNA is supported by a grant from the Canadian Institutes of Health Research with funding from several partners. Dr Nick W. Bray was supported by a 2018–2021 Ontario Graduate Scholarship (OGS); the “Fellowship in Care of the Older Adult” from the St. Joseph{\textquoteright}s Healthcare Foundation, Parkwood Institute, Division of Geriatric Medicine, University of Western Ontario; and the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794). Teresa Liu-Ambrose is a Canada Research Chair (Tier I) in Healthy Aging. Dr. Montero-Odasso{\textquoteright}s program in Gait and Brain Health is supported by grants from the Canadian Institute of Health Research (MOP 211220; PJT 153100), the Ontario Ministry of Research and Innovation (ER11–08–101), the Ontario Neurodegenerative Diseases Research Initiative (OBI 34739), the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794), and Department of Medicine Program of Experimental Medicine Research Award (POEM 768915), University of Western Ontario. He is the first recipient of the Schulich Clinician-Scientist Award. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to American Aging Association.",

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T2 - baseline results from the SYNERGIC Trial

AU - Bray, Nick W.

AU - Pieruccini-Faria, Frederico

AU - Witt, Suzanne T.

AU - Rockwood, Kenneth

AU - Bartha, Robert

AU - Doherty, Timothy J.

AU - Nagamatsu, Lindsay S.

AU - Almeida, Quincy J.

AU - Liu-Ambrose, Teresa

AU - Middleton, Laura E.

AU - Bherer, Louis

AU - Montero-Odasso, Manuel

N1 - Funding Information: The SYNERGIC Trial is funded by Canadian Consortium on Neurodegeneration in Aging (CCNA Grant# “FRN” CNA 137794). The CCNA is supported by a grant from the Canadian Institutes of Health Research with funding from several partners. Dr Nick W. Bray was supported by a 2018–2021 Ontario Graduate Scholarship (OGS); the “Fellowship in Care of the Older Adult” from the St. Joseph’s Healthcare Foundation, Parkwood Institute, Division of Geriatric Medicine, University of Western Ontario; and the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794). Teresa Liu-Ambrose is a Canada Research Chair (Tier I) in Healthy Aging. Dr. Montero-Odasso’s program in Gait and Brain Health is supported by grants from the Canadian Institute of Health Research (MOP 211220; PJT 153100), the Ontario Ministry of Research and Innovation (ER11–08–101), the Ontario Neurodegenerative Diseases Research Initiative (OBI 34739), the Canadian Consortium on Neurodegeneration in Aging (FRN CNA 137794), and Department of Medicine Program of Experimental Medicine Research Award (POEM 768915), University of Western Ontario. He is the first recipient of the Schulich Clinician-Scientist Award. Publisher Copyright: © 2022, The Author(s), under exclusive licence to American Aging Association.

PY - 2022

Y1 - 2022

N2 - Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson’s correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676

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