- Email: [email protected]
Entorhinal thickness mediates the relationship between hippocampus volume and default-mode network connectivity independently of amyloid burden in cognitively intact elderly
P106
IC-P-186
Alzheimer’s Imaging Consortium Poster Presentations: IC-P
STRATEGIC BRAIN AREAS FOR COGNITIVE DECLINE IN SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT: A DIFFUSION TENSOR IMAGING AND PET STUDY
Min-Jeong Kim1, Kyoung-Min Lee2, Young-Don Son3, Hyeon-Ae Jeon4, Sejin Yoo5, Ji-Young Kim6, Young-Bo Kim3, Zang-Hee Cho3, 1Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Neuroscience Research Institute, Gachon Medical School, Incheon, South Korea; 4Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 5Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, South Korea; 6Department of Neurology, Inje University Seoul Paik Hospital, Seoul, South Korea. Contact e-mail: kmjchh@gmail. com Background: Subcortical vascular cognitive impairment is known to be caused by subcortical ischemic changes that are presented as white matter hyperintensities, lacunar infarcts, and microbleeds on MRI. However, the specific brain area which is critical for clinical cognitive decline has not been revealed yet in subcortical vascular cognitive impairment. Here we aimed to investigate the difference of affected brain areas between those with and without clinical cognitive impairment in patients having subcortical ischemic changes on conventional MRI by using diffusion tensor imaging (DTI) and [18F]-Fluorodeoxygucose (FDG)-PET. Methods: 17 patients with both of subcortical vascular ischemic changes and clinical cognitive impairment, 12 patients with subcortical vascular changes but without cognitive impairment, and 10 normal healthy subjects underwent DTI and FDG-PET. Frational anisotropy (FA) of whole brain areas was compared among the groups by using tract-based spatial statistics. Cortical glucose metabolism was also compared among the groups by using 3-dimensional MRI-PET co-registration and spatial normalization. The statistical maps for significantly different areas were constructed. Results: Those with both subcortical ischemia and cognitive impairment showed significantly decreased FA value in the periventricular white matters including the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the corpus callosum compared to those without cognitive impairment. Those with cognitive impairment also showed significant cortical hypometabolism in the bilateral dorsal and ventral inferior frontal, the left dorsal inferior temporal areas compared to those without cognitive impairment. Comparison between normal control subjects and those with subcortical ischemia showed significant difference in more extensive and non-specific areas: white matter tracts including both periventricular and deep subcortical areas, and dorsal and ventral fronto-temporal gray matters. Conclusions: The major difference among those with and without cognitive impairment was mainly observed in the dorsal periventricular white matter tracts in DTI and the inferior fronto-temporal areas in PET. Since those areas are considered to mostly overlap with the well-known cortical and subcortical cholinergic pathways, subcortical vascular cognitive impairment could be mainly attributed to ischemic damages in the subcortical cholinergic fibers.
IC-P-187
ATHEROSCLEROTIC CALCIFICATION IS RELATED TO COGNITIVE DECLINE
Meike Vernooij1, Daniel Bos1, Albert Hofman2, Jacqueline Witteman2, Aad van der Lugt1, Mohammad Ikram1, 1Erasmus MC, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: Increasing evidence implicates atherosclerosis in the etiology of cognitive impairment and ultimately dementia, but longitudinal data are scarce. Also, it remains unclear whether atherosclerosis in different vessel beds affects cognitive decline differentially. In this study, we investigate the relationship between arterial calcification, as marker of atherosclerosis, in four vessel beds and cognitive decline over a 6 year interval. Methods:
From the population-based Rotterdam Study, 1858 participants (mean age 68.4 6 5.9 years) underwent computed tomography of the coronaries, aortic arch, extracranial and intracranial carotid arteries to quantify atherosclerotic calcification. At baseline and after six years of follow-up, cognition was assessed using the MMSE and a neuropsychological test battery that comprised the following domains: global cognition, memory, executive function and information processing speed. Per participant, we calculated the difference between both time points in standardized scores for each cognitive domain. Relationships between atherosclerotic calcification and cognitive decline were assessed using linear regression models and adjusted for age, sex, education and additionally for APOE-e4-status and cardiovascular risk factors. Results: Larger load of calcification in the coronary arteries, aortic arch and intracranial carotid arteries, but not in the extracranial carotid arteries, was associated with a decline in MMSE scores and decline in global cognitive function (see Figure). These associations seemed primarily driven by decline in executive function. Conclusions: Atherosclerosis is an important cause of cognitive decline and thus of interest as potential modifiable target for prevention of dementia.
IC-P-188
ENTORHINAL THICKNESS MEDIATES THE RELATIONSHIP BETWEEN HIPPOCAMPUS VOLUME AND DEFAULT-MODE NETWORK CONNECTIVITY INDEPENDENTLY OF AMYLOID BURDEN IN COGNITIVELY INTACT ELDERLY
Andrew Ward1, Elizabeth Mormino2, Aaron Schultz1, Trey Hedden3, Keith Johnson4, Reisa Sperling5, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2Massachusetts General Hospital, Boston, Massachusetts, United States; 3Martinos Center for Biomedical Imaging at Harvard University, Charlestown, Massachusetts, United States; 4MGH HMS, Boston, Massachusetts, United States; 5 Brigham and Women’s Hospital, Boston, Massachusetts, United States. Contact e-mail: [email protected] Background: Hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity are biomarkers that show significant declines with age, and are also implicated in Alzheimer’s disease. However, the relationships between these markers of AD development remain unresolved, especially within clinically normal individuals. Furthermore, our previous work indicates that entorhinal cortex (ERC) functional connectivity mediates the relationship between hippocampus and DMN during resting state. Here, we extend our previous functional results by assessing the relationship between brain structure in the MTL and DMN connectivity. Methods: Elderly subjects (n¼184, age65 years old, CDR¼0, within one SD of age- and education-adjusted norms on Logical Memory IIa) underwent MRI and amyloid-PET exams. ERC and HC measures were automatically computed by FreeSurfer v5.1 using MPRAGE T1-weighted images. A single measure of DMN connectivity was computed from two six-minute resting-state scans by averaging pairwise Fisher-z transformed correlations from three regions of interest: the posterior cingulate cortex (MNI 0, -53, 26), medial prefrontal cortex (MNI 0, 52, -6), and bilateral inferior parietal lobule (MNI -48, -62, 36; 46, -62, 32). Mediation was tested
Alzheimer’s Imaging Consortium Poster Presentations: IC-P for significance using a bootstrapping method (Preacher & Kelley, 2010) with 10000 iterations. Results: Both HC (P<0.005) and ERC (P<0.0001) were significantly related to DMN connectivity while controlling for age and total grey matter. HC (Figure 1A) and ERC (Figure 1B) show similar patters of relationship with the DMN at the map level. ERC mediates the relationship between HC and DMN connectivity as assessed by a bootstrapping method (mediation ratio¼0.42, indirect effect¼1.03*10 -4, confidence interval¼[3.35*10 -5 to 1.83*10 -5], p<0.001). Amyloid burden did not modify this effect. Conclusions: First, we find that structural measures of the MTL affect DMN connectivity above and beyond the effects of nonspecific grey matter and age. Second, we find further evidence for a structural/functional pathway between hippocampus and the DMN that is mediated by entorhinal cortex. Longitudinal analyses will elucidate the order in which these regions are impacted during AD development.
P107
sought to investigate linear and non-linear aging effects on the frontal cortex using a large dataset of healthy subjects. Methods: Structural MRI images of 385 healthy subjects from eight different datasets, all acquired using 1.5T GE Signa equipment. Gray matter (GM) volumes from selected frontal lobe portions (dorsomedial, dorsolateral and orbital frontal cortices) entered regression analyses with age as the main predictor, and scanning protocol as a confound covariate. Results: Age of subjects ranged from 18 to 87 years. Within the whole sample, the best-fit model for all frontal structures, with the exception of the left orbital frontal cortex, was a quadratic model of GM change across age range showing GM loss in ages > 35 years. Among subjects < 60 years, there was also a quadratic GM change through age range for the left dorsomedial and dorsolateral and right orbital frontal cortices, showing GM loss in ages > 28 years. However, within this subgroup, there was a linear relative preservation of GM through age for the right dorsomedial and dorsolateral frontal cortices. Within the elderly subgroup (> 60 years) there were quadratic GM variations in bilateral dorsomedial and dorsolateral frontal cortices across age, in which there was GM loss in ages > 70 years. Conclusions: Normal aging in the frontal cortex involves non-linear patterns of GM loss. However, normal ageing was not homogeneous across life span or within frontal cortical subregions. These findings are unlikely to have been biased by the inclusion of brain images acquired using different scanning protocols.
IC-P-190
HEALTHY AGING AFFECTS CHOLINERGIC FUNCTIONAL NETWORKS
Michel Grothe1, Ingo Kilimann2, Helmut Heinsen3, Lea Grinberg4, Eduardo Alho5, Edson Amaro, Jr.,6, Karlheinz Hauenstein7, Stefan Teipel8, 1 German Center for Neurodegenerative Diseases (DZNE), Rostock, Rostock, Germany; 2German Center for Neurodegenerative Disease (DZNE) and University Medicine Rostock, Rostock, Germany; 3University of Wuerzburg, W€urzburg, Germany; 4UCSF, San Francisco, California, United States; 5Julius-Maximilians-University, Wuerzburg, Wuerzburg, Germany; 6Department of Radiology, University of Sao Paulo, Medical School, Sao Paulo, Brazil; 7University of Rostock, Rostock, Germany; 8 University Medicine Rostock and DZNE Rostock, Rostock, Germany. Contact e-mail: [email protected]
A. Map-level effect of entorhinal thickness on DMN connectivity. B. Maplevel effect of hippocampus volume on DMN connectivity. Maps thresholded at P < 0.05 FDR corrected. IC-P-189
FRONTAL CORTEX AND NORMAL AGING: A VOXEL-BASED MORPHOMETRY MRI STUDY OF HEALTHY INDIVIDUALS
Pedro Rosa1, Priscila Serrano2, Pedro Curiati2, Luiz Kobuti Ferreira3, Marcus Zanetti2, Luciana Santos2, Fabio Duran2, Tania Alves2, Geraldo Busatto2, 1Neuroimaging Laboratory (LIM-21), Institute of Psychiatry , University of S~ ao Paulo, S~ao Paulo, Brazil; 2Neuroimaging Laboratory (LIM-21), S~ ao Paulo, Brazil; 3Neuroimaging Laboratory (LIM021), S~ ao Paulo, Brazil. Contact e-mail: [email protected] Background: A number of recent studies have investigated the effects of ageing on cortical structures, and much attention has been given to non-linear aging patterns, particularly in regard to the frontal lobe. This study
Background: The basal forebrain cholinergic system (BFCS) is selectively vulnerable to age-related neurodegenerative changes, and is early involved in Alzheimer’s disease (AD). Tracing experiments in animal models suggest a distinct corticotopy of projections from cholinergic cell clusters of the BFCS, but the organization of this system in the human brain is only insufficiently described. Resting-state functional MRI (rs-fMRI) has emerged as an in-vivo method to map functional connectivity (FC) in the human brain, which can be combined with novel in vivo markers of BFCS degeneration. Methods: Structural MRI and rs-fMRI scans were retrieved for 70 healthy subjects (age range: 20-85 years) from the International Neuroimaging Data-sharing Initiative (INDI). Rs-fMRI data was preprocessed using the DPARSFA toolbox in SPM8. Localizations of the rostral cholinergic nuclei Ch1-2, as well as the anterior-to-intermediate (Ch4a-i) and posterior (Ch4p) sections of the nucleus basalis, were identified using a newly created subregion-specific atlas of the BFCS based on combined histology and post mortem MRI in-cranio. Seed-to-voxel FC analysis was used to reveal nucleusspecific networks of interconnected brain regions, independently of age and gender (p(FWE)<0.05). Cross-sectional voxel-wise regression analyses were used to assess age-effects on connectivity strength within these networks (p(FDR)<0.05). Results: The different cholinergic nuclei showed distinct but partially overlapping FC networks. The Ch12 region showed prominent FC with the ventromedial prefrontal cortex (vmPFC), hippocampus and posterior cingulate (PC), resembling midline components of the default mode network (DMN). In contrast, the Ch4a-i nucleus appeared to be selectively connected to inferior parietal nodes of the DMN, in addition to vmPFC and anterior medial temporal regions. The Ch4p section also showed FC with medial temporal regions, but also to lateral temporal areas, as well as insular and dorsal anterior cingulate components of a previously described salience network. Marked changes in FC with age were only
IC-P-186
Alzheimer’s Imaging Consortium Poster Presentations: IC-P
STRATEGIC BRAIN AREAS FOR COGNITIVE DECLINE IN SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT: A DIFFUSION TENSOR IMAGING AND PET STUDY
Min-Jeong Kim1, Kyoung-Min Lee2, Young-Don Son3, Hyeon-Ae Jeon4, Sejin Yoo5, Ji-Young Kim6, Young-Bo Kim3, Zang-Hee Cho3, 1Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3Neuroscience Research Institute, Gachon Medical School, Incheon, South Korea; 4Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 5Interdisciplinary Program in Cognitive Science, Seoul National University, Seoul, South Korea; 6Department of Neurology, Inje University Seoul Paik Hospital, Seoul, South Korea. Contact e-mail: kmjchh@gmail. com Background: Subcortical vascular cognitive impairment is known to be caused by subcortical ischemic changes that are presented as white matter hyperintensities, lacunar infarcts, and microbleeds on MRI. However, the specific brain area which is critical for clinical cognitive decline has not been revealed yet in subcortical vascular cognitive impairment. Here we aimed to investigate the difference of affected brain areas between those with and without clinical cognitive impairment in patients having subcortical ischemic changes on conventional MRI by using diffusion tensor imaging (DTI) and [18F]-Fluorodeoxygucose (FDG)-PET. Methods: 17 patients with both of subcortical vascular ischemic changes and clinical cognitive impairment, 12 patients with subcortical vascular changes but without cognitive impairment, and 10 normal healthy subjects underwent DTI and FDG-PET. Frational anisotropy (FA) of whole brain areas was compared among the groups by using tract-based spatial statistics. Cortical glucose metabolism was also compared among the groups by using 3-dimensional MRI-PET co-registration and spatial normalization. The statistical maps for significantly different areas were constructed. Results: Those with both subcortical ischemia and cognitive impairment showed significantly decreased FA value in the periventricular white matters including the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the corpus callosum compared to those without cognitive impairment. Those with cognitive impairment also showed significant cortical hypometabolism in the bilateral dorsal and ventral inferior frontal, the left dorsal inferior temporal areas compared to those without cognitive impairment. Comparison between normal control subjects and those with subcortical ischemia showed significant difference in more extensive and non-specific areas: white matter tracts including both periventricular and deep subcortical areas, and dorsal and ventral fronto-temporal gray matters. Conclusions: The major difference among those with and without cognitive impairment was mainly observed in the dorsal periventricular white matter tracts in DTI and the inferior fronto-temporal areas in PET. Since those areas are considered to mostly overlap with the well-known cortical and subcortical cholinergic pathways, subcortical vascular cognitive impairment could be mainly attributed to ischemic damages in the subcortical cholinergic fibers.
IC-P-187
ATHEROSCLEROTIC CALCIFICATION IS RELATED TO COGNITIVE DECLINE
Meike Vernooij1, Daniel Bos1, Albert Hofman2, Jacqueline Witteman2, Aad van der Lugt1, Mohammad Ikram1, 1Erasmus MC, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: Increasing evidence implicates atherosclerosis in the etiology of cognitive impairment and ultimately dementia, but longitudinal data are scarce. Also, it remains unclear whether atherosclerosis in different vessel beds affects cognitive decline differentially. In this study, we investigate the relationship between arterial calcification, as marker of atherosclerosis, in four vessel beds and cognitive decline over a 6 year interval. Methods:
From the population-based Rotterdam Study, 1858 participants (mean age 68.4 6 5.9 years) underwent computed tomography of the coronaries, aortic arch, extracranial and intracranial carotid arteries to quantify atherosclerotic calcification. At baseline and after six years of follow-up, cognition was assessed using the MMSE and a neuropsychological test battery that comprised the following domains: global cognition, memory, executive function and information processing speed. Per participant, we calculated the difference between both time points in standardized scores for each cognitive domain. Relationships between atherosclerotic calcification and cognitive decline were assessed using linear regression models and adjusted for age, sex, education and additionally for APOE-e4-status and cardiovascular risk factors. Results: Larger load of calcification in the coronary arteries, aortic arch and intracranial carotid arteries, but not in the extracranial carotid arteries, was associated with a decline in MMSE scores and decline in global cognitive function (see Figure). These associations seemed primarily driven by decline in executive function. Conclusions: Atherosclerosis is an important cause of cognitive decline and thus of interest as potential modifiable target for prevention of dementia.
IC-P-188
ENTORHINAL THICKNESS MEDIATES THE RELATIONSHIP BETWEEN HIPPOCAMPUS VOLUME AND DEFAULT-MODE NETWORK CONNECTIVITY INDEPENDENTLY OF AMYLOID BURDEN IN COGNITIVELY INTACT ELDERLY
Andrew Ward1, Elizabeth Mormino2, Aaron Schultz1, Trey Hedden3, Keith Johnson4, Reisa Sperling5, 1Massachusetts General Hospital, Charlestown, Massachusetts, United States; 2Massachusetts General Hospital, Boston, Massachusetts, United States; 3Martinos Center for Biomedical Imaging at Harvard University, Charlestown, Massachusetts, United States; 4MGH HMS, Boston, Massachusetts, United States; 5 Brigham and Women’s Hospital, Boston, Massachusetts, United States. Contact e-mail: [email protected] Background: Hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity are biomarkers that show significant declines with age, and are also implicated in Alzheimer’s disease. However, the relationships between these markers of AD development remain unresolved, especially within clinically normal individuals. Furthermore, our previous work indicates that entorhinal cortex (ERC) functional connectivity mediates the relationship between hippocampus and DMN during resting state. Here, we extend our previous functional results by assessing the relationship between brain structure in the MTL and DMN connectivity. Methods: Elderly subjects (n¼184, age65 years old, CDR¼0, within one SD of age- and education-adjusted norms on Logical Memory IIa) underwent MRI and amyloid-PET exams. ERC and HC measures were automatically computed by FreeSurfer v5.1 using MPRAGE T1-weighted images. A single measure of DMN connectivity was computed from two six-minute resting-state scans by averaging pairwise Fisher-z transformed correlations from three regions of interest: the posterior cingulate cortex (MNI 0, -53, 26), medial prefrontal cortex (MNI 0, 52, -6), and bilateral inferior parietal lobule (MNI -48, -62, 36; 46, -62, 32). Mediation was tested
Alzheimer’s Imaging Consortium Poster Presentations: IC-P for significance using a bootstrapping method (Preacher & Kelley, 2010) with 10000 iterations. Results: Both HC (P<0.005) and ERC (P<0.0001) were significantly related to DMN connectivity while controlling for age and total grey matter. HC (Figure 1A) and ERC (Figure 1B) show similar patters of relationship with the DMN at the map level. ERC mediates the relationship between HC and DMN connectivity as assessed by a bootstrapping method (mediation ratio¼0.42, indirect effect¼1.03*10 -4, confidence interval¼[3.35*10 -5 to 1.83*10 -5], p<0.001). Amyloid burden did not modify this effect. Conclusions: First, we find that structural measures of the MTL affect DMN connectivity above and beyond the effects of nonspecific grey matter and age. Second, we find further evidence for a structural/functional pathway between hippocampus and the DMN that is mediated by entorhinal cortex. Longitudinal analyses will elucidate the order in which these regions are impacted during AD development.
P107
sought to investigate linear and non-linear aging effects on the frontal cortex using a large dataset of healthy subjects. Methods: Structural MRI images of 385 healthy subjects from eight different datasets, all acquired using 1.5T GE Signa equipment. Gray matter (GM) volumes from selected frontal lobe portions (dorsomedial, dorsolateral and orbital frontal cortices) entered regression analyses with age as the main predictor, and scanning protocol as a confound covariate. Results: Age of subjects ranged from 18 to 87 years. Within the whole sample, the best-fit model for all frontal structures, with the exception of the left orbital frontal cortex, was a quadratic model of GM change across age range showing GM loss in ages > 35 years. Among subjects < 60 years, there was also a quadratic GM change through age range for the left dorsomedial and dorsolateral and right orbital frontal cortices, showing GM loss in ages > 28 years. However, within this subgroup, there was a linear relative preservation of GM through age for the right dorsomedial and dorsolateral frontal cortices. Within the elderly subgroup (> 60 years) there were quadratic GM variations in bilateral dorsomedial and dorsolateral frontal cortices across age, in which there was GM loss in ages > 70 years. Conclusions: Normal aging in the frontal cortex involves non-linear patterns of GM loss. However, normal ageing was not homogeneous across life span or within frontal cortical subregions. These findings are unlikely to have been biased by the inclusion of brain images acquired using different scanning protocols.
IC-P-190
HEALTHY AGING AFFECTS CHOLINERGIC FUNCTIONAL NETWORKS
Michel Grothe1, Ingo Kilimann2, Helmut Heinsen3, Lea Grinberg4, Eduardo Alho5, Edson Amaro, Jr.,6, Karlheinz Hauenstein7, Stefan Teipel8, 1 German Center for Neurodegenerative Diseases (DZNE), Rostock, Rostock, Germany; 2German Center for Neurodegenerative Disease (DZNE) and University Medicine Rostock, Rostock, Germany; 3University of Wuerzburg, W€urzburg, Germany; 4UCSF, San Francisco, California, United States; 5Julius-Maximilians-University, Wuerzburg, Wuerzburg, Germany; 6Department of Radiology, University of Sao Paulo, Medical School, Sao Paulo, Brazil; 7University of Rostock, Rostock, Germany; 8 University Medicine Rostock and DZNE Rostock, Rostock, Germany. Contact e-mail: [email protected]
A. Map-level effect of entorhinal thickness on DMN connectivity. B. Maplevel effect of hippocampus volume on DMN connectivity. Maps thresholded at P < 0.05 FDR corrected. IC-P-189
FRONTAL CORTEX AND NORMAL AGING: A VOXEL-BASED MORPHOMETRY MRI STUDY OF HEALTHY INDIVIDUALS
Pedro Rosa1, Priscila Serrano2, Pedro Curiati2, Luiz Kobuti Ferreira3, Marcus Zanetti2, Luciana Santos2, Fabio Duran2, Tania Alves2, Geraldo Busatto2, 1Neuroimaging Laboratory (LIM-21), Institute of Psychiatry , University of S~ ao Paulo, S~ao Paulo, Brazil; 2Neuroimaging Laboratory (LIM-21), S~ ao Paulo, Brazil; 3Neuroimaging Laboratory (LIM021), S~ ao Paulo, Brazil. Contact e-mail: [email protected] Background: A number of recent studies have investigated the effects of ageing on cortical structures, and much attention has been given to non-linear aging patterns, particularly in regard to the frontal lobe. This study
Background: The basal forebrain cholinergic system (BFCS) is selectively vulnerable to age-related neurodegenerative changes, and is early involved in Alzheimer’s disease (AD). Tracing experiments in animal models suggest a distinct corticotopy of projections from cholinergic cell clusters of the BFCS, but the organization of this system in the human brain is only insufficiently described. Resting-state functional MRI (rs-fMRI) has emerged as an in-vivo method to map functional connectivity (FC) in the human brain, which can be combined with novel in vivo markers of BFCS degeneration. Methods: Structural MRI and rs-fMRI scans were retrieved for 70 healthy subjects (age range: 20-85 years) from the International Neuroimaging Data-sharing Initiative (INDI). Rs-fMRI data was preprocessed using the DPARSFA toolbox in SPM8. Localizations of the rostral cholinergic nuclei Ch1-2, as well as the anterior-to-intermediate (Ch4a-i) and posterior (Ch4p) sections of the nucleus basalis, were identified using a newly created subregion-specific atlas of the BFCS based on combined histology and post mortem MRI in-cranio. Seed-to-voxel FC analysis was used to reveal nucleusspecific networks of interconnected brain regions, independently of age and gender (p(FWE)<0.05). Cross-sectional voxel-wise regression analyses were used to assess age-effects on connectivity strength within these networks (p(FDR)<0.05). Results: The different cholinergic nuclei showed distinct but partially overlapping FC networks. The Ch12 region showed prominent FC with the ventromedial prefrontal cortex (vmPFC), hippocampus and posterior cingulate (PC), resembling midline components of the default mode network (DMN). In contrast, the Ch4a-i nucleus appeared to be selectively connected to inferior parietal nodes of the DMN, in addition to vmPFC and anterior medial temporal regions. The Ch4p section also showed FC with medial temporal regions, but also to lateral temporal areas, as well as insular and dorsal anterior cingulate components of a previously described salience network. Marked changes in FC with age were only