Basal Forebrain and Hippocampus as Predictors of Conversion to Alzheimer's Disease in Patients with Mild Cognitive Impairment - A Multicenter DTI and Volumetry Study.

Published on Jan 1, 2015in Journal of Alzheimer's Disease3.909
· DOI :10.3233/JAD-150063
Katharina Brueggen10
Estimated H-index: 10
(German Center for Neurodegenerative Diseases),
Martin Dyrba14
Estimated H-index: 14
(German Center for Neurodegenerative Diseases)
+ 8 AuthorsStefan J. Teipel65
Estimated H-index: 65
Background: Hippocampal grey matter (GM) atrophy predicts conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Pilot data suggests that mean diffusivity (MD) in the hippocampus, as measured with diffusion tensor imaging (DTI), may be a more accurate predictor of conversion than hippocampus volume. In addition, previous studies suggest that volume of the cholinergic basal forebrain may reach a diagnostic accuracy superior to hippocampal volume in MCI. Objective: The present study investigated whether increased MD and decreased volume of the hippocampus, the basal forebrain and other AD-typical regions predicted time to conversion from MCI to AD dementia. Methods: 79 MCI patients with DTI and T1-weighted magnetic resonance imaging (MRI) were retrospectively included from the European DTI Study in Dementia (EDSD) dataset. Of these participants, 35 converted to AD dementia after 6-46 months (mean: 21 months). We used Cox regression to estimate the relative conversion risk predicted by MD values and GM volumes, controlling for age, gender, education and center. Results: Decreased GM volume in all investigated regions predicted an increased risk for conversion. Additionally, increased MD in the right basal forebrain predicted increased conversion risk. Reduced volume of the right hippocampus was the only significant predictor in a stepwise model combining all predictor variables. Conclusion: Volume reduction of the hippocampus, the basal forebrain and other AD-related regions was predictive of increased risk for conversion from MCI to AD. In this study, volume was superior to MD in predicting conversion.
📖 Papers frequently viewed together
9,609 Citations
69.4k Citations
128 Citations
#1Derek L. G. HillH-Index: 119
#2Adam J. Schwarz (Eli Lilly and Company)H-Index: 45
Last. Diane Stephenson (Critical Path Institute)H-Index: 25
view all 32 authors...
Background: Regulatory qualification of a biomarker for a defined context of use provides scientifically robustassurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development. Methods: The Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampalvolumeasabiomarkerforenrichingclinicaltrialsinsubjectswithmildcognitiveimpairme...
59 CitationsSource
#1Ingo Kilimann (German Center for Neurodegenerative Diseases)H-Index: 15
#1Ingo Kilimann (University of Rostock)H-Index: 14
Last. Stefan J. Teipel (University of Rostock)H-Index: 55
view all 16 authors...
Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI- based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-d...
94 CitationsSource
#1Martin Dyrba (German Center for Neurodegenerative Diseases)H-Index: 14
#2Michael Ewers (LMU: Ludwig Maximilian University of Munich)H-Index: 56
Last. Stefan J. Teipel (University of Rostock)H-Index: 55
view all 16 authors...
Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of m...
71 CitationsSource
#1Michel J. Grothe (University of Rostock)H-Index: 33
#2Helmut Heinsen (University of Würzburg)H-Index: 55
Last. Stefan J. Teipel (University of Rostock)H-Index: 55
view all 3 authors...
Abstract Recent evidence from cross-sectional in vivo imaging studies suggests that atrophy of the cholinergic basal forebrain (BF) in Alzheimer's disease (AD) can be distinguished from normal age-related degeneration even at predementia stages of the disease. Longitudinal study designs are needed to specify the dynamics of BF degeneration in the transition from normal aging to AD. We applied recently developed techniques for in vivo volumetry of the BF to serial magnetic resonance imaging scans...
116 CitationsSource
#1Lin Zhuang (UNSW: University of New South Wales)H-Index: 10
#2Perminder S. Sachdev (UNSW: University of New South Wales)H-Index: 126
Last. Wei Wen (UNSW: University of New South Wales)H-Index: 72
view all 7 authors...
Background Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.
92 CitationsSource
#1Georg M. Kerbler (UQ: University of Queensland)H-Index: 4
#2Adam S. Hamlin (UQ: University of Queensland)H-Index: 20
Last. Elizabeth J. Coulson (UQ: University of Queensland)H-Index: 34
view all 7 authors...
Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. T...
19 CitationsSource
#1Kalina Venkova-Hristova (University of Toledo Medical Center)H-Index: 2
#2Alexandar ChristovH-Index: 7
Last. Kenneth Hensley (UT: University of Toledo)H-Index: 51
view all 5 authors...
Please consider the following changes in Table 1. Table 1 Mendelian and non-Mendelian loci known to cause FALS or confer risk for SALS. Information in this table reproduces content in Tables 7 and 8 from Lill and Bertram, 2011 ([2], and databases therein). Polymorphisms in the VEGF promoter ...
55 CitationsSource
#1Per Selnes (Ahus: Akershus University Hospital)H-Index: 16
#2Anders M. Fjell (University of Oslo)H-Index: 76
Last. Tormod Fladby (Ahus: Akershus University Hospital)H-Index: 35
view all 9 authors...
Abstract Background To determine whether white matter (WM) memory network changes accompany early cognitive impairment and whether these changes represent early, pathologically independent axonal affection, we combined WM diffusion tensor imaging and cortical morphometric measurements of normal control subjects, patients with only subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). Methods We included 66 patients with SCI or MCI and 21 control subjects from a university-ho...
61 CitationsSource
#1Michel J. GrotheH-Index: 33
#2Helmut HeinsenH-Index: 55
Last. Stefan J. TeipelH-Index: 65
view all 3 authors...
Background The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative changes during normal aging as well as severe atrophy in Alzheimer's disease (AD). However, there is a controversy regarding how the cholinergic lesion in AD relates to early and incipient stages of the disease. In vivo imaging studies on the structural integrity of the BFCS in normal and pathologic aging are rare. Methods We applied automated morphometry techniques in combination with high-di...
164 CitationsSource
#1Davangere P. Devanand (Columbia University)H-Index: 23
#1Devangere P. Devanand (Columbia University)H-Index: 68
Last. Bradley S. Peterson (Columbia University)H-Index: 98
view all 6 authors...
Abstract Objective Using MRI surface morphometry mapping, to evaluate local deformations of the hippocampus, parahippocampal gyrus, and entorhinal cortex in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Methods Baseline brain MRI with surface morphological analysis was performed in 130 outpatients with MCI, broadly defined, and 61 healthy controls followed for an average of 4 years in a single site study. Results Patients with MCI differed from controls ...
94 CitationsSource
Cited By34
#1Maria F. Falangola (MUSC: Medical University of South Carolina)H-Index: 16
#2Xingju Nie (MUSC: Medical University of South Carolina)H-Index: 8
Last. Jens H. Jensen (MUSC: Medical University of South Carolina)H-Index: 52
view all 7 authors...
Degeneration of the basal forebrain (BF) is detected early in the course of Alzheimer's disease (AD). Reduction in the number of BF cholinergic (ChAT) neurons associated with age-related hippocampal cholinergic neuritic dystrophy is described in the 3xTg-AD mouse model; however, no prior diffusion MRI (dMRI) study has explored the presence of BF alterations in this model. Here we investigated the ability of diffusion MRI (dMRI) to detect abnormalities in BF microstructure for the 3xTg-AD mouse m...
#1Franziska E Hildesheim (SUNY: State University of New York System)
#1Franziska E. Hildesheim (SUNY: State University of New York System)H-Index: 1
Last. Niels Bergsland (SUNY: State University of New York System)H-Index: 40
view all 8 authors...
BACKGROUND The nucleus basalis of Meynert (NBM), representing the major source of cerebral cholinergic innervations, is vulnerable to neurodegeneration in Alzheimer's and Parkinson's disease. OBJECTIVE To determine associations between NBM properties and cognitive outcomes in patients with multiple sclerosis (PwMS). METHODS 84 PwMS and 19 controls underwent 3T MRI, the Paced Auditory Serial Addition Test (PASAT) and subtests of the Brief International Cognitive Assessment for MS (BICAMS). NBM vo...
Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the formation of senile plaques and neurofibrillary tangles, followed by neurodegeneration, which leads to cognitive decline and eventually death. Introduction. In AD, pathological changes occur many years before disease onset. Since disease-modifying therapies may be the most beneficial in the early stages of AD, biomar...
2 CitationsSource
#1David B. Stone (Johnson & Johnson Pharmaceutical Research and Development)
#2Sephira G. Ryman (Johnson & Johnson Pharmaceutical Research and Development)
Last. Alzheimer’s Disease Neuroimaging Initiative (LRRI: Lovelace Respiratory Research Institute)
view all 6 authors...
Identifying biomarkers that can assess the risk of developing Alzheimer's Disease (AD) remains a significant challenge. In this study, we investigated the integrity levels of brain white matter in 34 patients with mild cognitive impairment (MCI) who later converted to AD and 53 stable MCI patients. We used diffusion tensor imaging (DTI) and automated fiber quantification to obtain the diffusion properties of 20 major white matter tracts. To identify which tracts and diffusion measures are most r...
#1Gemma Lombardi (UniFI: University of Florence)H-Index: 10
#2Giada Crescioli (UniFI: University of Florence)H-Index: 8
Last. Graziella FilippiniH-Index: 44
view all 11 authors...
BACKGROUND: Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of...
16 CitationsSource
#1Meret Herdick (University of Rostock)H-Index: 1
#2Martin Dyrba (German Center for Neurodegenerative Diseases)H-Index: 14
Last. Michel J. Grothe (CSIC: Spanish National Research Council)H-Index: 33
view all 36 authors...
Abstract Background Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer’s disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes. Methods Participants included healthy controls, and subjects with subjective cognitive dec...
1 CitationsSource
#1Avinash Chandra ('KCL': King's College London)H-Index: 5
#2George Dervenoulas ('KCL': King's College London)H-Index: 5
view all 4 authors...
Research utilizing magnetic resonance imaging (MRI) has been crucial to the understanding of the neuropathological mechanisms behind and clinical identification of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). MRI modalities show patterns of brain damage that discriminate AD from other brain illnesses and brain abnormalities that are associated with risk of conversion to AD from MCI and other behavioural outcomes. This review discusses the application of various MRI techniques to...
35 CitationsSource
#1Qi Feng (ZJU: Zhejiang University)H-Index: 2
#2Mei Wang (ZJU: Zhejiang University)H-Index: 2
Last. Zhongxiang Ding (ZJU: Zhejiang University)H-Index: 8
view all 9 authors...
Alzheimer's disease (AD) is a neurodegenerative disease with main symptoms of chronic primary memory loss and cognitive impairment. The study aim is to investigate the correlation between hippocampal functional connectivity (FC) and MRI radiomic features in AD. A total of 67 AD patients and 44 normal controls (NC) were enrolled in this study. Using one method of resting-state functional MRI (rs-fMRI), the whole-brain FC with bilateral hippocampus as seed was performed, and the FC values were ext...
4 CitationsSource