Neuroimaging in Neurodegenerative Dementias
Neurodegenerative dementias are characterized by insidious onset and gradual progression of cognitive dysfunction, initially relatively focal with respect to cognitive domains and brain regions involved. Neuroimaging techniques have contributed enormously to both our understanding of large-scale network specificity in neurodegenerative syndromes and our ability to make clinical diagnoses of syndromes such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), posterior cortical atrophy (PCA), logopenic primary progressive aphasia (PPA), agrammatic PPA, semantic dementia (SD), behavioral variant frontotemporal dementia (bvFTD), corticobasal syndrome (CBS), and progressive supranuclear palsy syndrome (PSPS). More importantly, rapid advances in imaging and computational techniques promise to improve our ability to make pathologic diagnoses of AD, DLB, and frontotemporal lobar degeneration (FTLD) pathologies in vivo at an early stage of illness. Neuroimaging is thus integral to the development and application of disease modifying therapies for neurodegenerative illnesses.
Rapid advances in our understanding of neurodegenerative dementias in recent years have translated into a change in the clinical approach to a patient presenting with changes in cognition. Whereas previous practice frequently entailed "excluding treatable causes" and lumping the remaining cases together as presenile dementia, senile dementia, or possibly Alzheimer's disease or multiinfarct dementia, dementia specialists in the present day actively endeavor to predict a patient's underlying neuropathology utilizing history, examination, and biomarker data. Advances in neuroimaging techniques, particularly magnetic resonance imaging (MRI), have contributed immensely not only to our understanding of clinical/pathologic relationships in the research setting, but also to our ability to arrive at clinical diagnoses in daily practice.
Most neurodegenerative dementias are characterized by a clinical course of insidious onset and gradual progression of symptoms over months to years. Thought previously to engender global cognitive dysfunction even in the early stages of illness, neurodegenerative processes are now recognized to produce focal cognitive dysfunction initially, corresponding to a circumscribed initial distribution of pathology. Localization of cognitive dysfunction via history and examination and localization of neuronal dysfunction and/or neurodegeneration with neuroimaging thus empower clinicians to distinguish between unique clinical syndromes with characteristic early anatomic signatures (Table 1).
Converging evidence from cellular and systems-level neuroscience suggests that the anatomic signatures of neurodegenerative processes correspond to large-scale networks in the brain. This concept has been articulated as the network degeneration hypothesis, summarized in Fig. 1 and by Pievani and colleagues. Neuroimaging techniques have played a central role in exploring this hypothesis. Functional connectivity MRI (fcMRI), examining interregional correlations in neuronal activity with blood-oxygen-level-dependent (BOLD) signal, has revolutionized our understanding of large-scale functional brain networks. Supporting a relationship between large-scale networks and neurodegeneration, studies have demonstrated correspondence between distributions of pathology and network anatomy, for example, overlap between the distribution of fibrillar amyloid-β protein (Aβ) as revealed by [C] Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the default network, a set of brain regions including the medial frontal cortex, posterior cingulate, precuneus, lateral parietal cortex, and medial temporal cortex. Employing resting state fcMRI and voxel-based morphometry (VBM), Seeley and colleagues demonstrated concordance between patterns of volume loss in AD, bvFTD, SD, nonfluent aphasia, and CBS and dissociable networks comprising regions that covary both functionally and structurally in healthy control subjects. These studies have laid the foundation for investigating potential mechanisms underlying network degeneration, which eventually could help to explain different patterns of neurodegeneration with different types of neuropathology.
(Enlarge Image)
Figure 1.
Network degeneration hypothesis. *Discussed in Zhou et al.
Neuroimaging has thus furthered progress toward the ultimate goal of predicting neuropathology in vivo in single subjects. At present, imaging techniques have value in predicting progression to dementia in individuals with mild cognitive impairment (MCI), a condition representing an intermediate stage between cognitive changes present with aging and those fulfilling criteria for dementia. Given evidence that neuropathologic processes start years in advance of clinical symptoms and the widely accepted principle that early intervention will confer a greater likelihood of success with disease-modifying treatments, presymptomatic detection of disease using a combination of neuroimaging and other biomarkers will likely represent a cornerstone of clinical management in the future.
This review summarizes characteristic neuroimaging features for more common neurodegenerative dementia clinical syndromes (Table 1). Imaging modalities already approved for and established in clinical use are presented, along with salient information about selected research imaging techniques that may have an increasing role in clinical practice in the future (Table 2).
Abstract and Introduction
Abstract
Neurodegenerative dementias are characterized by insidious onset and gradual progression of cognitive dysfunction, initially relatively focal with respect to cognitive domains and brain regions involved. Neuroimaging techniques have contributed enormously to both our understanding of large-scale network specificity in neurodegenerative syndromes and our ability to make clinical diagnoses of syndromes such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), posterior cortical atrophy (PCA), logopenic primary progressive aphasia (PPA), agrammatic PPA, semantic dementia (SD), behavioral variant frontotemporal dementia (bvFTD), corticobasal syndrome (CBS), and progressive supranuclear palsy syndrome (PSPS). More importantly, rapid advances in imaging and computational techniques promise to improve our ability to make pathologic diagnoses of AD, DLB, and frontotemporal lobar degeneration (FTLD) pathologies in vivo at an early stage of illness. Neuroimaging is thus integral to the development and application of disease modifying therapies for neurodegenerative illnesses.
Introduction
Rapid advances in our understanding of neurodegenerative dementias in recent years have translated into a change in the clinical approach to a patient presenting with changes in cognition. Whereas previous practice frequently entailed "excluding treatable causes" and lumping the remaining cases together as presenile dementia, senile dementia, or possibly Alzheimer's disease or multiinfarct dementia, dementia specialists in the present day actively endeavor to predict a patient's underlying neuropathology utilizing history, examination, and biomarker data. Advances in neuroimaging techniques, particularly magnetic resonance imaging (MRI), have contributed immensely not only to our understanding of clinical/pathologic relationships in the research setting, but also to our ability to arrive at clinical diagnoses in daily practice.
Most neurodegenerative dementias are characterized by a clinical course of insidious onset and gradual progression of symptoms over months to years. Thought previously to engender global cognitive dysfunction even in the early stages of illness, neurodegenerative processes are now recognized to produce focal cognitive dysfunction initially, corresponding to a circumscribed initial distribution of pathology. Localization of cognitive dysfunction via history and examination and localization of neuronal dysfunction and/or neurodegeneration with neuroimaging thus empower clinicians to distinguish between unique clinical syndromes with characteristic early anatomic signatures (Table 1).
Converging evidence from cellular and systems-level neuroscience suggests that the anatomic signatures of neurodegenerative processes correspond to large-scale networks in the brain. This concept has been articulated as the network degeneration hypothesis, summarized in Fig. 1 and by Pievani and colleagues. Neuroimaging techniques have played a central role in exploring this hypothesis. Functional connectivity MRI (fcMRI), examining interregional correlations in neuronal activity with blood-oxygen-level-dependent (BOLD) signal, has revolutionized our understanding of large-scale functional brain networks. Supporting a relationship between large-scale networks and neurodegeneration, studies have demonstrated correspondence between distributions of pathology and network anatomy, for example, overlap between the distribution of fibrillar amyloid-β protein (Aβ) as revealed by [C] Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the default network, a set of brain regions including the medial frontal cortex, posterior cingulate, precuneus, lateral parietal cortex, and medial temporal cortex. Employing resting state fcMRI and voxel-based morphometry (VBM), Seeley and colleagues demonstrated concordance between patterns of volume loss in AD, bvFTD, SD, nonfluent aphasia, and CBS and dissociable networks comprising regions that covary both functionally and structurally in healthy control subjects. These studies have laid the foundation for investigating potential mechanisms underlying network degeneration, which eventually could help to explain different patterns of neurodegeneration with different types of neuropathology.
(Enlarge Image)
Figure 1.
Network degeneration hypothesis. *Discussed in Zhou et al.
Neuroimaging has thus furthered progress toward the ultimate goal of predicting neuropathology in vivo in single subjects. At present, imaging techniques have value in predicting progression to dementia in individuals with mild cognitive impairment (MCI), a condition representing an intermediate stage between cognitive changes present with aging and those fulfilling criteria for dementia. Given evidence that neuropathologic processes start years in advance of clinical symptoms and the widely accepted principle that early intervention will confer a greater likelihood of success with disease-modifying treatments, presymptomatic detection of disease using a combination of neuroimaging and other biomarkers will likely represent a cornerstone of clinical management in the future.
This review summarizes characteristic neuroimaging features for more common neurodegenerative dementia clinical syndromes (Table 1). Imaging modalities already approved for and established in clinical use are presented, along with salient information about selected research imaging techniques that may have an increasing role in clinical practice in the future (Table 2).