Prior to neuroimaging, the patient with cognitive decline should have had: ⢠A detailed history of the features of cognitive and functional decline. ⢠A full medical ...
NEUROLOGY
NEUROIMAGING IN DEMENTIA: A PRACTICAL GUIDE Neuroimaging, whilst not a diagnostic test alone. as part of a multimodal approach can influence a timely diagnosis of dementia. The aim of this article is to describe a series of cases of patients presenting with cognitive impairment, and their corresponding neuroimaging, to improve understanding and diagnosis of dementia, its subtypes and its mimics. Lauren
The Alzheimer's Society reports that in the UK
M.~~!~~~ ......... alone there are currently 800,000 people living with Academic Clinical Fellow in Geriatrics, Royal Devon and Exeter Hospital, Exeter
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Tarun Kuruvilla Consultant Radiologist, Gloucestershire Hospitals NHS Foundation Trust
dementia. This is projected to rise to over one million people by 2021.1 Yearly, 60,000 deaths are reported to be directly attributable to dementia. Research suggests that delaying the onset of dementia by five years would reduce deaths directly attributable to dementia by 30,000 a year.2 Neuroimaging, whilst not a diagnostic test alone, as part of a multimodal approach can influence a timely diagnosis of dementia. According to NICE guidelines structural imaging should be used in the assessment of people with suspected dementia to exclude other cerebral pathologies and to help establish the subtype diagnosis. 3 While magnetic resonance imaging (MRI) is the preferred modality to aid early diagnosis and detect subcortical vascular changes, the modern multi-slice computed tomograph (CT) has been shown to have excellent reliability, compared to MRI, for detecting hippocampal atrophy, global cortical atrophy and white matter changes and may be more widely available and cheaper to access. 4 Radiological findings are utilised to support a clinical diagnosis within a comprehensive assessment framework. Prior to neuroimaging, the patient with cognitive decline should have had: • A detailed history of the features of cognitive and functional decline • A full medical and psychiatric history • A mental state examination including cognitive tests • Physical examination • Laboratory investigations; full blood count, U&E, LFf, TFf, serum cakium, folate and vitamin B12 as amm1mum. The role of neuroimaging in the diagnosis of dementia is multi-factorial. • To exclude potentially treatable conditions. For example; a brain tumour or subdural haematoma • To aid the subtyping of dementia • To monitor the progression of disease • To ensure participants meet inclusion/exclusion criteria, and as outcome measures in research trials.
While a thorough medical and psychiatric history, clinical examination and laboratory investigations may identify most of the causes of reversible cognitive impairment, systematic reviews suggest that up to 5% of cases of suspected dementia have conditions that required structural neuroimaging to assist with diagnosis. 2 Further, Gifford et al showed that there is considerable uncertainty in the evidence behind clinical prediction rules to identify which patients with dementia should undergo neuroimaging and the application of these rules may miss patients with potentially reversible conditions, hence it is widely accepted that a structural imaging procedure should be performed routinely in each patient with suspected dementia. 5 The aim of this article is to describe a series of cases of patients presenting with cognitive impairment, and their corresponding neuroimaging, to improve understanding and diagnosis of dementia, its subtypes and its mimics. Case studies will be presented followed by the appropriate imaging, a discussion and key learning points.
Case study 1 A 72-year-old female was referred to the GP by her husband who reported subtle personality changes over the preceding six-months. Her husband reported that she had become increasingly emotionally unstable, often crying and laughing at inappropriate times. On questioning she reported a constant dull headache. Her past medical history included diet controlled type 2 diabetes and a lumpectomy 20 years ago for locally invasive breast cancer. On examination there was no evidence of focal neurological signs.
Imaging This axial CT head with contrast shows an obvious lesion in the left and right frontal regions. The patient was diagnosed with calcified metastatic disease and referred to the neurosurgeons for excision (see Figure 1).
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NEUROLOGY
Figure 1. lhis axial er head with contrast shows lesions in the left and right frontal regions (metastasis).
Discussion Cognitive disorders (including behavioural decline) can result from intracranial tumours, even in the absence of focal neurological signs on examination. This is potentially reversible, and expedient structural imaging of the brain can identify these lesions and allow for appropriate treatment. In this case, a constant dull headache was an important feature suggesting intracranial pathology. Contrast imaging was required to show the extent of the abnormal pathology.
Key points
Figure 2. lhis axial er image shows symmetrical widening of the ventricles (NHP). In a globally atrophied brain we would expect to see proportionally large sulci to match the large ventricles. Here the ventricles are disproportionally large (see Figure2).
Discussion The diagnosis in this case is one of normal pressure hydrocephalus (NPH). The presenting triad of cognitive decline, gait instability and urinary incontinence are characteristic. The patient was referred to neurosurgery for consideration of ventricular shunting.
• Neuroimaging in patients with symptoms of cognitive impairment helps to eliminate potentially reversible causes of dementia.
Key points
Case study 2
• In this case a history of cognitive impairment, urine incontinence and ataxia should have alerted the physician to a diagnosis of NHP.
A 75-year-old male presented after his family expressed concern that he had been muddling up the names of his children and grandchildren. The family reported that the memory problems had started around eight months ago. He had recently been in hospital following a fall, and had been complaining of incontinence of urine. He had a history of benign prostatic hypertrophy, hypertension and a total hip replacement. On examination he had a broad based gait, and a markedly delayed 10 metre walking test.
Imaging This axial CT image shows symmetrical widening of the ventricles. Ventricular widening can be seen in cases of global atrophy. However, by looking at the brain tissue closest to the skull, you can see clearly that there is very little cerebrospinal fluid around the outside of the brain.
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• Accurate history taking is an important part of the diagnosis of dementia.
Case study 3 A 62-year-old male is referred to the GP by his daughter. She reported that her father had a 12-month history of short-term memory loss. She reported that she would call him up every evening, but he was unable to remember one phone call to the next. He would forget arrangements they would make and appointments with friends. He lacked insight into his memory problems attributing it to normal ageing. He had a past medical history of diet controlled diabetes, right total knee replacement and chronic obstructive pulmonary disease. On examination he scored 20/30 on a MMSE. He had no focal neurology on examination.
NEUROLOGY Figure 4. This axial er scan shows evidence of global atrophy. The degree of atrophy is age related and normal scans for patients aged 70, 80, 90 and 100 years are shown (normal scans).
Figure 3. These coronal and axial er head scans show evidence of global atrophy, as evidenced by deep sulci and apparent loss of volume. The atrophy is most prominent in the medial temporal lobes (AD).
Imaging This coronal CT head scan shows evidence of global atrophy, as evidenced by deep sulci and apparent loss of volume. The atrophy appears most prominent in the (medial) temporal lobes, bilaterally (see Figure 3).
Hippocampal atrophy, best seen on coronal MRI or er, has emerged as a sensitive and specific marker for Alzheimer's disease (AD) 6• 7 and is recognised as a biomarker of neuronal injury in the updated National Institute on Aging and the Alzheimer's Association workgroup (NIA-AA) diagnostic criteria.8 The overall sensitivity and specificity of hippocampal atrophy for detecting mild to moderate AD versus controls was 85% and 88% in a meta-analysis. 9
Key points • In AD coronal MRI or CT scans show evidence of medical temporal lobe atrophy (MTA). • MTA is often missed on axial images.
Discussion
Case study 4
The diagnosis here is Alzheimer's disease (AD). The .diagnosis is suspected from the long history of shortterm memory (STM) loss, the impact of this on daily function and the characteristic CT findings.
A 90-year-old female presented to her GP with concerns about her memory. She reported going to the shops, but forgetting why she was there. She also reported sometimes leaving her glasses behind at friends' houses
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NEUROLOGY Key points • Over the age of 90 years approximately 50% of patients will have evidence of cognitive impairment, this is commonly of mixed pathology.
Case study S A 35-year-old gentleman presented to his GP on the advice of his occupational health department. He had worked as an IT technician for a decade and was well respected. Over the last two years there had been a gradual change in his behaviour. He was reported for being rude, and his friends stated that whilst he had always been tidy his house was now dilapidated. He had stopped taking care of his appearance and personal hygiene, and had become more withdrawn and apathetic.
Imaging
Figure 5. This axial FLAIR MRI of fronto-temporal dementia shows a line dividing the frontal-temporal region and the parietal-occipital regions, with greater volume loss in the fronto-temporal region (FTD).
and missing the occasional appoinrment. She had previously had a pulmonary embolism following a total knee replacement 10 years ago and age related macular degeneration. On examination she had a slightly low blood pressure at 105/68mmHg and evidence of corneal arcus, but no focal neurological signs. She scored 28/30 onherMMSE.
Figure 5 is an axial MRI image. It is a FLAIR (fluid attenuated inversion recovery) sequence, used to enhance hyper-intensive signals. The relevant feature is the cerebral atrophy more pronounced in frontal and temporal regions. A line has been drawn between the fronto-temporal region and the parietal-occipital region, to highlight the difference in the gyri thickness, and the size of the sulci. The gyri at the very front of the brain (frontotemporal region) are markedly narrowed compared to the back of the brain (parietal-occipital region). The gyri in the right temporal lobe are sharp and deeply indented and are described as "knife-like" (see figure 5).
Discussion
This axial CT scan shows evidence of global atrophy. This atrophy appears increased compared to the normal scans of patients in their 70's and 80's (shown below). However, this degree of atrophy would be considered normal for a patient of 90 years. The atrophy is symmetrical from left to right and from front to back and there does not appear to be any areas of focal atrophy. The sulci are deep, but this is consistent throughout the scan (see Figure 4).
This image shows significant atrophy throughout all of the frontal and temporal lobes, particularly in the right hemisphere. The diagnosis in this case is frontotemporal dementia (FTD), behavioural variant. The clinical picture of FTD is typically an insidious, progressive decline in interpersonal skills, personal care and executive function. It is a more common cause of dementia in adults of working age, and is often misdiagnosed as depression or personality disorder. The atrophy may be seen on both CT and standard MRI, however it is more pronounced on the MRI FLAIR sequence.
Discussion
Key points
Imaging
This is a normal brain scan for a 90-year-old patient. This also correlates to her normal score on the MMSE (28/30) and her history, which is consistent with normal ageing and does not demonstrate significant functional impairment. It is important to have an awareness of normal-for-age images on both axial and coronal CT scans to distinguish these from pathological scans. Global atrophy increases with age and it is important to regularly review normal brains, to establish a point of reference.
• Behavioural and personality changes in younger patients should alert the clinician to hunt for a diagnosis. Neuroimaging often plays an important role in this work up.
Case study 6 A 65-year-old, afro-caribbean female was referred to TIA clinic with an episode of expressive dysphasia. Her symptoms lasted 15 minutes. She had a history
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NEUROLOGY
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densities throughout the brain, corresponding to multiple domains. In the widely used National Institute for Neurological Disorders and Stroke with the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) diagnostic criteria for Vascular Dementia (VD), structural neuroimaging is essential for the diagnosis by demonstrating a link between dementia and cerebrovascular disease in the form of large vessel infarcts; single strategically placed infarcts; multiple basal ganglia and white matter lacunae; or extensive peri-ventricular and deep white matter ischaemia. 10 Classic features suggestive of vascular dementia on CT (or MRI) include bilateral multiple infarcts located in the dominant hemisphere and limbic structures, multiple lacunar strokes, or periventricular white matter lesions extending into the deep white matter. 11 These findings can be seen on this axial scan (see Figure 6).
Discussion Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to ProStrakan Ud on 01896 664000.
Further information is available on request from: ProStrakan Ltd, Galabank Business Park, Galashiels, TDl lQH, UK. Legal cat•gory: P. Please consult Summary of Product Characteristics before prescribing, particularly in relation to side-effects, precautions and contraindications. Information about these products, including adverse reactions, precautions, contraindications and method of use can be found at httpJ/www.medicines.org.uk/emc. Marketing Authorisation Holder: ProStrakan Ltd, Galashiels, TD l lOH, UK. Adcal is a registered trademark of ProStrakan Ltd. Date of preparation: January 2015. Code: MOOl/1461
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With the history of cardiovascular disease and evidence of widespread hyper-intensities on CT, this would be consistent with a diagnosis of vascular dementia. Vascular dementia (VD) is often said to be the second most common form of dementia after AD. Most estimates range between 11 % and 18 % for VD and between 22% and 34% for 'mixed dementia' that typically reflects features of both Alzheimer's and vascular disease. 1 VD is commonly understood as a condition in which cognitive impairment results from deleterious effects
NEUROLOGY
Alzheimer's Disease I scan
Probable DLB scan
Figure 7. This shows abnormal asymmetrical signal uptake in the substantia nigra on a DATScan (PD). of vascular disease processes on brain structure and function. The vascular disease processes that give rise to cognitive decline include; cerebrovascular diseases involving either larger or smaller cerebral arteries, and/or cerebrovascular injury from vascular events occurring outside the cerebrum.
Key points • Vascular dementia is more common in men, Asian and Afro-Caribbean groups. 12 • Classical CT/MRI findings show widespread multiple infarcts located in the dominant hemisphere or limbic system.
Case study 7 A 67-year-old male attended the GP surgery with his wife. Over the past six months she had been increasingly concerned about his behaviour. He had been accusing her of having an affair with her deceased ex-husband. He appeared to be paranoid of male visitors and she was concerned he was having hallucinations of her ex-husband being in the house. On examination he was very reluctant to engage in conversation, and difficult to examine. It was apparent that he had marked slowness of his movements on repetitive testing and seemed to have very expression-less facial features. However, any other signs could not be elicited.
Imaging This is a specific type of SPECT scan, known as a DaTscan, showing abnormal asymmetrical signal in the substantia nigra, consistent with a diagnosis of dementia with Lewy bodies (DLB). Distinguishing DLB from AD and VD is difficult on standard CT or MRl. DaTscans are the imaging of choice for DLB, showing asymmetrical dopamine transporter uptake. In a recent meta-analysis of 419 subjects, the estimated pooled sensitivity of DaTSCAN in differentiating DLB versus no DLB was 86.5% [95% Confidence Intervals (Cl): 72-94.1 %], with a specificity of 93.6% (95% Cl: 88.5- 96.6%) 13 (see Figure 7).
NEUROLOGY Discussion The diagnosis in this case is dementia with Lewy bodies (DLB). Clues to differentiate it from AD include; fluctuations in cognitive function with varying levels of alertness and attention, excessive daytime drowsiness, visual hallucination and Parkinsonian motor features. Although extrapyramidal features may occur late in the course of AD, they appear relatively early in DLB.
appropriate imaging modality. The imaging must then be interpreted in the context of the whole clinical picture. Detailed imaging plays an important role in excluding other causes, defining, and subtyping the dementia and for research. Having a good understanding of the role of neuroimaging in dementia enables us to optimally manage patients with dementia syndromes using an individualised approach.
Key points
Conflict of interest: none declared.
• Conventional brain imaging scans eg. MRI and CT usually do not show any characteristic changes.
References
• DAT scans are the modality of choice for diagnosing DLB, showing asymmetrical dopamine uptake.
Review of NICE guidelines According to NICE guidelines structural imaging should be used in the assessment of people with suspected dementia to exclude other cerebral pathologies and to help establish the subtype diagnosis. Magnetic resonance imaging (MRI) is the preferred modality to assist with early diagnosis and detect subcortical vascular changes, although computed tomography (CT) scanning can (and often is) used. Specialist advice should be taken when interpreting scans in people with learning disabilities. In a recent large scale meta-analysis that included 38 studies there was insufficient evidence to suggest MRI is superior to CT. The results showed CT specificity and sensitivity for hyper-intensity was 71 % and 55% respectively, versus 95% and 26% for MRI. 14 Dementia can be caused by different aetiological processes that can be difficult to distinguish clinically, particularly in the early stages of the disease. AD is the most common, followed by VD, mixed pathology and LBD. Making a formal diagnosis is important as evidence shows AD in the early stages is responsive to Acetyl-cholinesterase inhibitors. Furthermore understanding the prevalence of various subtypes will help in future research. While neuroimaging is important in the diagnosis of dementia syndromes it should not be taken in isolation and it is important to consider the diagnostic criteria, which comprises appropriate history, examination, serology and imaging. These criteria include have been outlined in the paper Standardised Diagnostic Criteria for Dementia. 15 Accurate and appropriate diagnosis allows individually tailored care plans that help physicians, carers and staff plan for the future.
Conclusion This case series highlights the difficulties we have when posed with patients presenting with signs and symptoms of cognitive impairment. The key is to perform a through and accurate history and examination combined with the
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1. Dementia 2012: A National Challenge. Document produced by the Alzheimer's Association, UK, 2012. 2. http://alzheimers.org.uk/site/scripts/documents_info. php?documentlD=412 (Accessed 20/5/15) 3. Dementia: A NICE-SCIE guideline on supporting people with dementia and their carers in health and social care. National Collaborating Centre for Mental Health UK. British Psychological Society, 2007. 4. Wattjes MP, Henneman WJ, van der Flier WM, et al. Diagnostic imaging of patients in a memory clinic: comparison of MR imaging and 64-detector row CT. Radiology 2009; 253(1): 174-86 5. Gifford DR, Holloway RG, Vickery BG. Systematic review of clinical prediction rules for neuroimaging in the evaluation of dementia. Arch Intern Med 2000; 160: 2855-62 6. Jack CR Jr., Petersen RC, O'Brien PC, Tangalos EG. MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease. Neurology 1992; 42: 183-88 7. de Leon MJ, George AE, Stylopoulos LA, et al. Early marker for Alzheimer's disease: the atrophic hippocampus. Lancet 1989; 2: 672- 73 8. McKhann GM, Knopman OS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the national institute on Aging and the Alzheimer's Association workgroup. Alzheimer's Dement 2011; 7(3): 263-69 9. Scheltens P, Fox N, Barkhof N, De Carli C. Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion. Lancet Neurology 2002; 1: 13-21 10.Roman GC, Tatemichi TK, Erkinjutti T, et al. Vascular dementia: Diagnostic criteria for research studies: Repott of the NINDS-AIREN International Workshop. Neurology 1994; 43: 250-60 11.Parizel MP, van den Hauwe L, de Belder 1'~ et al. Magnetic Imaging of the brain. Clinical MR Imaging 2010:P107-195 12.Dementia does not discriminate. All-party parliamentary group on dementia. Alzheimer's society 2013. 13.Papathanasiou ND, Boutsiadis A, Dickson J, Bomanji JB. Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta-analysis of published studies. Parkinsonism relat. Disord 2012; 18(3); 225-29 14.Beynon R, Sterne JAC, Wilcox G, et al. Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis. BMC Neurology 2012; 12-33 15.Rainey K, Kuruvilla T. Standardised diagnostic criteria for dementia. GM 2013; 43: 24- 29
