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|Radiological Imaging of Dementia|
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Northeast Florida Medicine, Vol. 70, No. 2, February 2019
UF Health Jacksonville
Address Correspondence to:
Patrick Natter, MD
Date of Release: February 1, 2019
Date Credit Expires: February 1, 2021
Estimated Completion Time: 1 hour
The Duval County Medical Society (DCMS) is proud to provide its members with free continuing medical education (CME) opportunities in subject areas mandated and suggested by the State of Florida Board of Medicine to obtain and retain medical licensure. The DCMS would like to thank the St. Vincent’s Healthcare Committee on CME for reviewing and accrediting this activity in compliance with the Accreditation Council on Continuing Medical Education (ACCME). This issue of Northeast Florida Medicine includes an article, “Radiological Imaging of Dementia” authored by Patrick Natter, MD, which has been approved for 1 AMA PRA Category 1 credit.TM For a full description of CME requirements for Florida physicians, please visit www.dcmsonline.org.
Patrick Natter, MD, Assistant Professor of Radiology, UF Health – Jacksonville
The number of patients with dementia continues to increase significantly and is projected to reach 131 million worldwide by 2050. Associated costs of dementia are staggering at $818 billion worldwide in 2016. The large majority of patients with dementia have not received a diagnosis and mixed dementia pathologies are much more common than pure forms. It is important that patients receive an accurate diagnosis of dementia for prognosis purposes and this can be difficult due to clinical overlap of multiple dementias. Imaging has the potential to help differentiate between types of dementia in its current state with more promising imaging advances on the horizon. Imaging also has the ability to exclude treatable causes of patient symptoms who could present similar to dementia.
1. To understand the main objective in imaging of dementia is to exclude treatable causes of the patient's clinical symptoms.
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Patrick Natter, MD reports no significant relations to disclose, financial or otherwise, with an commercial supporter or product manufacturer associated with this activity.
Disclosure of Conflicts of Interest:
St. Vincent’s Healthcare (SVHC) requires speakers, faculty, CME Committee and other individuals who are in a position to control the content of this educational activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly evaluated by SVHC for fair balance, scientific objectivity of studies mentioned in the presentation and educational materials used as basis for content, and appropriateness of patient care recommendations.
Joint Sponsorship Accreditation Statement:
This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of St. Vincent’s Healthcare and the Duval County Medical Society. St. Vincent’s Healthcare designates this educational activity for a maximum of 1 AMA PRA Category 1 credit.TM Physicians should only claim credit commensurate with the extent of their participation in the activity.
Dementia is a condition characterized by progressive cognitive decline, and encompasses several subtypes of dementia, each with varying etiologies. While clinical findings are considered the primary factor in differentiating subtypes of dementia, radiological imaging of dementia continues to progress with ongoing research and imaging advances. Certain patterns of cerebral atrophy or molecular imaging uptake can help delineate dementias. This article reviews the typical imaging patterns for the four most common types of dementia and briefly discusses these types of dementia.
Dementia is a progressive medical illness that causes cognitive decline from a previous level of performance in one or more cognitive domains. Dementia is caused by multiple etiologies, all of which are progressive illnesses.1 Dementia can affect memory, thinking, behavior, and everyday activities.1 Dementia typically affects the elderly; however, 2-10 percent of cases start before the age of 65.1 Approximately 47 million people now live with dementia worldwide.2 This is projected to increase to 131 million by 2050.2 The estimated worldwide cost of dementia was $818 billion as of 2016.2 The large majority of patients with dementia have not received a diagnosis.2
The most common types of dementia include Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia.1 Alzheimer’s disease is overall the most common at 50-75 percent with vascular dementia the second most common at 20-30 percent.1 Mixed dementia pathologies are much more common than pure forms.1 Radiological imaging of the brain can be helpful in dementia; however, clinical findings should be the primary tool for delineating different dementia etiologies. One of the main objectives in imaging is the exclusion of treatable causes of the patient’s clinical symptoms such as normal pressure hydrocephalus, intracranial hemorrhage, or intracranial tumor.3
Alzheimer’s disease is the most common dementia. With this type, patients have progressive debilitating symptoms including memory loss, confusion, language dysfunction, apathy, and depression.1 There are significant genetic risk factors for Alzheimer’s disease, particularly regarding the Apolipoprotein E (APOE) gene.1 There are multiple proposed modifiable risk factors including smoking, alcohol intake, physical activity, diet, and presence of cognitive stimulation; however, only smoking cessation is strongly evidenced as a modifiable risk factor for dementia.1 In Alzheimer’s disease pathology, patients have beta amyloid plaques with neurofibrillary tangles within the brain.1 The amyloid plaques and neurofibrillary tangles are associated with the progressive loss of neurons with resultant cerebral volume loss.1 The underlying disease process also increases the risk of ischemic changes due to progressive disease of the arterial vasculature.1 The underlying brain pathology likely develops over 20-30 years before the onset of clinical symptoms.1
Magnetic Resonance Imaging (MRI) in Alzheimer’s disease demonstrates cerebral atrophy most prominently in the hippocampal formations which are present in the medial temporal lobes. There is a correlation with memory loss as hippocampal volume loss progresses.4 Cortical cerebral atrophy, greater than age based controls, is also present in the medial temporal lobes.5 There can also be associated parietal lobe volume loss.3 Continued research and development of software is needed to specifically analyze hippocampal volume loss on MRI images due to its significant involvement in Alzheimer’s.5 Additionally, MRI images show a correlation with associated greater ventricular volume due to the adjacent cerebral volume loss causing perceived enlargement of the ventricles.5 Structural measures of the medial temporal lobe on MRI using software analysis can predict cognitive decline but biomarkers from multiple modalities are a better predictor overall.4 MRI T2 weighted images demonstrate parietal and temporal volume loss with associated marked hippocampal volume loss (Figure 1).
Figure 1: T2-weighted MRI images of the brain in a patient with Alzheimer’s disease demonstrate temporal lobe volume loss and moderate hippocampal volume loss (short arrow on left image). Additionally, there is parietal volume loss evident on the right image (arrow).
More recent advances in Alzheimer’s imaging have been made using molecular imaging. Imaging of Alzheimer’s with Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG) demonstrates decreased FDG uptake in the parietotemporal lobes and posterior cingulate cortex as compared to the remaining cerebral cortex.6 A more recent advance in Alzheimer’s disease imaging is imaging of amyloid plaques and neurofibrillary tangles using PET imaging. Two amyloid imaging markers include [18F]FDDNP and [11C]PIB (Pittsburgh Compound B). PET scans using the amyloid imaging markers correlate with cognitive performance in normal elderly and mild cognitive impairment (MCI) subjects.5 Genetic risk factors for Alzheimer’s disease are related to the PET signal of both [18F]FDDNP and [11C]PIB markers in cognitively intact older adults.5 [11C]PIB levels also can predict conversion from normal cognition to MCI and Alzheimer’s disease.5 Figure 2 demonstrates the typical pattern of FDG-PET uptake in Alzheimer’s disease with decreased parietal temporal lobe uptake.
Figure 2: Multiple images from a PET CT of the head in a patient with Alzheimer’s disease demonstrate decreased uptake in the parietal and temporal lobes. Decreased uptake is seen in the medial temporal lobe on the left image (short arrow). Decreased uptake is present in the bilateral parietal lobes on the middle image (thin arrows). On the right image, there is decreased uptake in the parietal and temporal lobes which is evident on the 3D reconstructed image from the PET data (short arrows).
Vascular dementia is the second most common cause of dementia after Alzheimer’s disease.1,7 Vascular dementia affects cognitive abilities, particularly executive functioning.7 Patients can have slowed thinking, memory loss, depression, anxiety, disorientation, and loss of executive functioning among other symptoms.7 Vascular dementia is seen in patients with previous chronic ischemic changes of the brain which may be the result of a single infarct, multiple infarcts, or underlying diffuse chronic microvascular changes.1 Patients can have multiple cortical or lacunar infarcts which result from underlying vessel disease, cardiac, or systemic etiologies.1 Risk factors include general risk factors for ischemic stroke such as hypertension, cardiac disease, diabetes, and metabolic syndrome among others.7 However, infarcts and chronic ischemic changes alone on imaging is not sufficient for the diagnosis of vascular dementia as infarction and chronic ischemic changes are very common in the elderly.1 The imaging findings must be correlated with the clinical symptoms of dementia. The time course and pattern of development of the dementia is likely to be more variable than Alzheimer’s disease and the dementia can be progressive with a stepwise course.1 However, Alzheimer’s and vascular dementia can have clinically similar symptoms and may coexist in many patients, complicating the diagnosis.7 Figure 3 demonstrates extensive nonspecific white matter changes, likely due to chronic ischemic changes, with an area of lacunar infarct which could be seen on imaging of patients with vascular dementia although must be correlated with clinical findings.
Figure 3: FLAIR MRI image of the brain demonstrates extensive nonspecific white matter changes (short arrow) likely due to chronic ischemic changes. Additionally, there is a lacunar infarct in the right periventricular white matter (thin arrow).
Frontotemporal dementia (FTD) is a term which refers to a group of dementias typically characterized by progressive deficits in behavior, executive function, and/or language.8 Frontotemporal dementia is common and frequently seen in patients younger than 65.8 Making this diagnosis can be challenging as the symptoms of FTD can overlap with psychiatric disorders.8 There are multiple subtypes of FTD depending on the specific clinical deficits and areas of the brain initially affected. Three clinical variants include behavioral-variant, non-fluent variant primary progressive aphasia, and semantic-variant primary progressive aphasia.8 Behavioral-variant is associated with behavioral deficits such as personality changes, disinhibition, apathy, and executive deficits.8 Patients can also have socially inappropriate behavior and can develop upper and lower motor symptoms.8 Early parkinsonism can be present in up to 20 percent of patients with FTD.8 Primary progressive aphasia patients have an insidious progressive decline in linguistic skills and can later have behavioral abnormalities.8 Non-fluent variant primary progressive aphasia is characterized by slow, halting, and labored speech production with misuse or omission of grammar. The semantic variant presents with semantic aphasia with anomia, word finding difficulties, and impaired word comprehension.8 Additional subtypes and patterns of frontotemporal dementia have been described and are occasionally included under FTD; however, the additional types will not be discussed for the purposes of this article. Genetics and a family history of dementia appear to be important risk factors for FTD.8 Pathologically, FTD patients have neuronal loss, gliosis, and microvacuolar changes in the frontotemporal region.8
On imaging, FTD patients have resultant cortical atrophy which is greatest involving the frontal and temporal lobes.8,9,10 Frontoinsular region atrophy is especially indicative.8 Although different subtypes can have different atrophy patterns, there is variable appearance and considerable overlap so it is more important that the radiologist comments on frontotemporal atrophy overall, rather than the specific subtype.3 FDG-PET imaging demonstrates decreased metabolism in the frontal and temporal lobes. FDG-PET imaging can also demonstrate reduced uptake in the medial thalamus, amygdala, and in the anterior cingulate cortex.6 Amyloid PET tracer imaging can be helpful to distinguish between Alzheimer’s disease and FTD with uptake expected in Alzheimer’s disease and not in FTD.8 Figure 4 demonstrates moderate volume loss concentrated in the frontal and temporal lobes in a patient with FTD.
Figure 4: FLAIR MRI images of the brain in a patient with FTD demonstrate moderate frontal cerebral volume loss (short arrow on left image) and moderate temporal cerebral volume loss (short arrow on right image).
Dementia with Lewy bodies (DLB) can be characterized by cognitive fluctuation, visual hallucinations, and motor parkinsonism.11 Clinically, there can be overlap with Parkinson’s disease and Alzheimer’s disease, and DLB can be frequently misdiagnosed as Alzheimer’s.12 Both DLB and Parkinson’s tend to present in older patients although onset before 65 years of age is not uncommon and both are more common in males.12 In DLB, dementia occurs before or concurrently with parkinsonism or within one year of the onset of motor symptoms.12,13 However, not all DLB patients develop parkinsonism.12,13 Parkinson’s disease dementia is a different entity and refers to patients with Parkinson’s disease who develop dementia one year or later after established Parkinson’s disease.12,14 Pathologically, in DLB there are alpha-synuclein neuronal inclusions and Lewy neurites which are present in the brain tissue with neuronal loss.12 Most cases of DLB are sporadic but rare genetic autosomal dominant inheritance has been reported.12 There are, however, genetic risk factors which have been reported.12
DLB imaging with MRI demonstrates relative preservation of the volume of the medial temporal lobes including the hippocampus as compared to Alzheimer’s disease.11 There is also typically less pronounced cerebral atrophy overall as compared to Alzheimer’s disease.11 Since there is no focal area of cerebral atrophy specific for DLB, MRI alone is less helpful for the diagnosis of DLB compared with other dementias with specific areas of cerebral atrophy. PET imaging can demonstrate occipital lobe decreased uptake using FDG-PET.12 Also, the posterior cingulate island sign can be seen on FDG-PET which reflects relatively preserved metabolism in the posterior cingulate region.3,12 Marked reduction of dopaminergic activity in the basal ganglia is the most characteristic finding of DLB which is seen on molecular imaging.11 This can be visualized using single-photon emission computed tomography (SPECT) imaging using the 123FP-CIT ligand which demonstrates reduced uptake in the caudate and putamen as compared with Alzheimer’s disease and normal controls.11 Figure 5 demonstrates the FDG-PET findings in DLB with decreased occipital lobe uptake.
Figure 5: PET CT image of the head in a patient with DLB demonstrates decreased uptake in the bilateral occipital lobes (short arrows).
Imaging of dementia continues to advance with further research being performed to better delineate and identify different types of dementia by imaging. Imaging can be used for problem solving and to help exclude treatable etiologies which could present similar to dementia. There are certain patterns of cerebral atrophy and molecular imaging uptake which can help differentiate dementias; however, many imaging patterns overlap and imaging is typically not definitive. Many patients can also have mixed type dementias which further complicates imaging differentiation. Further research will be necessary for more accurate delineation and potentially early detection of dementia before the appearance of clinical symptoms.
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11. Mak E, Su L, Williams GB, et al. Neuroimaging characteristics of dementia with lewy bodies. Alzheimers Res Ther. 2014 April 09;6(2):18.
12. Walker Z, Possin KL, Boeve BF, et al. Lewy body dementias. Lancet. 2015 October 24;386(10004):1683-97.
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14. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with parkinson's disease. Mov Disord. 2007 September 15;22(12):1689,707; quiz 1837.