Neuroimaging in Dementia

Abstract and Introduction

Abstract

Although the diagnosis of dementia still is primarily based on clinical criteria, neuroimaging is playing an increasingly important role. This is in large part due to advances in techniques that can assist with discriminating between different syndromes. Magnetic resonance imaging remains at the core of differential diagnosis, with specific patterns of cortical and subcortical changes having diagnostic significance. Recent developments in molecular PET imaging techniques have opened the door for not only antemortem but early, even preclinical, diagnosis of underlying pathology. This is vital, as treatment trials are underway for pharmacological agents with specific molecular targets, and numerous failed trials suggest that earlier treatment is needed. This article provides an overview of classic neuroimaging findings as well as new and cutting-edge research techniques that assist with clinical diagnosis of a range of dementia syndromes, with an emphasis on studies using pathologically proven cases.

Introduction

The diagnosis of dementia is becoming increasingly reliant on a broad range of neuroimaging techniques, and this is reflected in several updated diagnostic criteria.^[1,2] Neuroimaging enhances the accuracy of diagnoses for distinct dementia subtypes. The recent failures of treatment trials for Alzheimer's disease (AD)^[3] indicate that earlier intervention, and therefore earlier diagnosis, may be critical to treatment success. Early diagnosis can be facilitated by neuroimaging techniques that can detect the earliest pathological and metabolic alterations that occur in neurodegenerative disease.

In this review, we discuss clinically relevant neuroimaging findings in a wide range of dementia syndromes, as well as cutting-edge techniques that are gaining traction in research. As we move toward the age of treatments designed for specific molecular targets (e.g., tau and amyloid), there is a growing need to move beyond simply classifying syndromes based entirely on clinical phenotypes to predicting underlying pathologies with greater precision using imaging, genetic, cerebrospinal fluid (CSF), and other objective markers of disease. In this review, we try to distinguish between imaging findings in pathologically proven versus clinically based diagnoses, placing particular emphasis on neuroimaging in pathologically confirmed cases as well as longitudinal neuroimaging studies. Dementia and related syndromes discussed in this review include AD, the frontotemporal dementia (FTD) spectrum, primary progressive aphasias (PPA), vascular dementia (VaD), Lewy body disease (LBD) and Parkinson's disease dementia (PDD), rapidly progressing dementias (RPD), normal pressure hydrocephalus (NPH), and cerebellar disorders. Other dementing conditions, including neurodegeneration with brain iron accumulation (NBIA) and chronic traumatic encephalopathy (CTE), are not covered here to allow for a greater depth of coverage of the more common and established causes of dementia. We conclude with a review of neuroimaging biomarkers of neurodegenerative diseases that are being developed in research, with a focus on structural and functional connectivity.

Table 1. UCSF 2017 Proposal of MRI Criteria for JCD Diagnosis
Diagnosis	UCSF 2017 Modified JCD MRI criteria^a
MRI definitely JCD	DWI^b > FLAIR cortical ribboning^c hyperintensity in:
	1. Classic pathognomonic: cingulate,^d striatum, and > 1 neocortical gyrus (often precuneus, angular, superior parietal, superior frontal, middle frontal, or lateral temporal gyrus)
	a. Supportive for subcortical^e involvement:
	i. Striatum with decreasing anterior–posterior gradient
	ii. Corresponding ADC hypointensity
	b. Supportive for cortical involvement:
	i. Asymmetric involvement of midline neocortex or cingulate^d
	ii. Sparing of precentral gyrus^f
	iii. Corresponding ADC cortical ribboning hypointensity
	2. Cortex only ( > 3 gyri); see supportive for cortex (above)
MRI probably JCD	1. Unilateral striatum or cortex (≤ 3 gyri); see supportive for subcortical and cortex (above)
	2. Bilateral striatum (see supportive for subcortical) or posteromedial thalamus; see supportive for subcortical (above)
	3. DWI > FLAIR hyperintensities only in limbic areas, with corresponding ADC hypointensity^g
MRI probably not JCD	1. Only FLAIR/DWI abnormalities only in limbic areas, where hyperintensity can be normal (e.g., insula, anterior cingulate, and hippocampi), and ADC map does not show corresponding restricted diffusion (hypointensity)
	2. DWI hyperintensities due to artifact (signal distortion); see other MRI issues (below)
	3. FLAIR > DWI hyperintensities^h; see other MRI issues (below)
MRI definitely not JCD	1. Normal
MRI definitely not JCD	2. Abnormalities not consistent with JCD
Other MRI issues	In prolonged courses of sJCD (~ >1 year), brain MRI might show significant atrophy with loss of DWI hyperintensity, particularly in areas previously with restricted diffusion.
Other MRI issues	To help distinguish abnormality from artifact, obtain b2000 diffusion sequences in multiple directions (e.g., axial and coronal).

Abbreviations: ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; JCD, Jakob–Creutzfeldt disease; MRI, magnetic resonance imaging.
^aModified from Vitali et al 2011.²¹⁵
^bRecommended minimum standard diffusion sequence parameters to best identify cortical ribboning: axial and coronal DWI/ADC b = 1000 second cm2 or b = 2000 second cm2, depending on scanner field strength and capabilities to achieve satisfactory image quality. At 3T, b = 2000 may be preferred due to higher contrast to background for abnormal gray matter diffusion.
^cInvolvement of cortical gray matter with sparing of underlying or adjacent white matter.
^dMid and posterior cingulate preferred over anterior due to anterior air-brain artifact especially on axial acquisition (anterior acceptable if coronal acquisition). Can be symmetric, but if so prefer ADC hypointensity correlate.
^eSubcortical = deep nuclei, in decreasing order of frequency caudate, putamen, thalamus (posteriomedial or diffuse), globus pallidus (rare). ADC often shows corresponding and earlier involvement than DWI.
^fIf precentral gyrus is preferentially involved consider nonprion diagnoses (e.g., seizures and Wernicke's).
^gDWI > FLAIR with reduced ADC in limbic or other cortical regions also can occur in HSV encephalitis^360,361 and seizures^362,363 depending on clinical picture, these should be ruled out.
^hConsider T2-shine through.³⁶⁴

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Neuroimaging in Dementia

Abstract and Introduction

Abstract

Introduction

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