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Radiol Case Rep
Radiol Case Rep
Radiology Case Reports
1930-0433
Elsevier

S1930-0433(24)00673-3
10.1016/j.radcr.2024.07.087
Case Report
Roles of arterial spin labelling in cognitive impairment: Case series
Hanapi Nurhusna Adibah ad
Halim Sanihah Abdul bde
Razak Asrenee Ab cde
Sapiai Nur Asma drnurasma@usm.my
ade⁎
a Department of Radiology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
b Department of Internal Medicine/Neurology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
c Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
d Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Health Campus, Jalan Raja Perempuan Zainab II, 16150 Kota Bharu, Kelantan, Malaysia
e Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia
⁎ Corresponding author. drnurasma@usm.my
10 8 2024
11 2024
10 8 2024
19 11 47364740
5 3 2024
15 7 2024
16 7 2024
© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
According to the most recent edition of the DSM V, neurocognitive disorder (NCD), formerly referred to as dementia, is a debilitating condition that progressively diminishes quality of life. It impacts both physical and cognitive domains, including memory and aberrant behavior. If usual presentation is uncertain, perfusion, functional, and molecular imaging are useful. Gold standard marker for the diagnosis of Alzheimer's disease (AD) is FDG PET imaging. Recent studies have shown promising results, whereby the cerebral blood flow in arterial spin labeling (ASL) of MRI and the hypometabolism FDG PET both show a consistent regional abnormality. Therefore, ASL MRI imaging carries a potential role in assisting diagnosis of neurocognitive disorder.

Keywords

Neurocognitive disorder
Dementia
Arterial spin labeling
Cerebral blood flow
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pmcIntroduction

Dementia affects around 50 million people worldwide, and this number is expected to double by 2040 [1]. It is becoming a global crisis of epidemic proportions. According to the WHO guide “Towards a Dementia Plan,” 63% of dementia cases come from low- and middle-income countries. A recent analysis projects that 152 million individuals will be affected by dementia by 2050, leading to a significant fiscal burden.

Neurocognitive disorders (NCD), including dementia, interfere with higher cortical functions. AD is the most common form, accounting for 60%-70% of cases, with vascular risk factors playing a role. Neuroimaging techniques like computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are used to assess the anatomical and functional aspects of the disease [2].

Fluorodeoxyglucose positron emission tomography (FDG PET) has been extensively researched for diagnosing neurocognitive disorders. Recent studies suggest that arterial spin labeling MRI (ASL MRI) may provide similar data by evaluating cerebral blood flow (CBF) [3]. The findings from ASL MRI are consistent with those from PET analysis.

Here we report 3 cases of cognitive memory impairment with interesting ASL findings.

Case report

Case 1

A 74-year-old lady with underlying metabolic risk factors. She has a history of latent syphilis and completed treatment previously with oral Doxycycline in 2019. She has presented with aggressive behaviors with on-and-off psychotic symptoms since November 2022. Her family also noticed gradual memory impairment since 2020. She was initially treated for moderate dementia with BPSD and started on tab Seroquel and Donepezil. Mini-Mental State Examination (MMSE) shows a total score of 20 out of 30 (mild score). Poor recall memory with a lack of orientation to time and place. She was electively admitted to intravenous Rocephine for treatment of neurosyphilis and completed a 2-week course of antibiotics. MRI Brain shows atrophy of medial temporal lobe and bilateral parietal lobe with few foci deep white matter hyperintensities on T2W/FLAIR sequences (Fig. 1). Decreased hippocampal height, increased width of choroid fissure and bilateral temporal horn suggestive medial temporal atrophy (MTA) score 3. Overlapping features of possible Alzheimer's Disease and small vessel disease on the conventional MRI. ASL imaging gives additional information, it shows significantly reduced cerebral blow flow at bilateral parietal, occipital, medial temporal lobe and part of bifrontal region (Fig. 2). This findings suggest possible of more to AD changes.Fig. 1 (A) MRI brain FLAIR (Axial): Few foci of deep white matter hyperintensities (arrow). (B) MRI brain FLAIR (Coronal): Decreased hippocampal height (arrow), increased width of choroid fissure and bilateral temporal horn-MTA score 3. (C) MRI brain T1 (Axial): Generalized bilateral mild cerebral atrophy.

Fig 1

Fig. 2 MRI brain fused ASL perfusion with FLAIR axial imaging reveals significantly reduced cerebral blood flow of the bilateral parietal, occipital, and part of frontal regions (arrow).

Fig 2:

Case 2

A 49-year-old lady who works as a teacher presents with gradual worsening of cognitive decline for the past year. She is easily forgetful, needs assistance for her daily activities, and cannot complete simple tasks. She also complained of feeling stressed since 2018, triggered by the sudden death of her husband and by the work environment. She noted a low mood, feeling worthless, and easily irritable. She also has a low appetite and no motivation to go to work. Denies any suicidal behavior or thoughts. Premorbidly, she is cheerful and friendly. MMSE shows a total score of 22 (mild score). She was reviewed by the psychiatric team and treated as major depressive disorder (MDD). She was started on oral escitalopram and given psychoeducation and psychotherapy. MRI brain shows mild atrophy bilateral parietal with mild widening of choroid fissure suggestive global cortical atrophy (GCA) scale 1 and MTA score 1. Concurrent reduced cerebral blood flow at the bilateral parietal mainly inferior region only on ASL sequences (Fig. 3). MRI findings are suggestive of early changes in neurocognitive disorder, possible of mid cognitive impairment (MCI). During her latest clinic follow-up, her mood was improving, and they were training for her cognitive function.Fig. 3 (A) MRI brain T1 (Axial): Opening of sulci of bilateral parietal region, GCA scale-1. (B) MRI brain FLAIR (Coronal oblique): Symmetrical widening of choroid fissure, MTA score 1. (C) MRI brain Fused ASL perfusion with FLAIR axial imaging shows hypoperfusion of bilateral parietal region (arrow).

Fig 3:

Case 3

A 66 years old, lady with underlying diabetes mellitus, hypertension, chronic kidney disease stage 4, previously has left cerebellar bleed in July 2022. She shows progressive decline in memories and behavioral changes since 2021. She is experiencing auditory hallucinations. She requires assistance for her daily living activities. MMSE score is 19 She was started on Oral donapezil, however unable to tolerate the side effects. MRI shows generalized volume loss of gyri bilateral cerebral hemisphere suggestive of moderate cerebral atrophy, GCA scale 2. Presence beginning confluence white matter hyperintensities at bilateral frontal and parietal lobes with irregular periventricular white matter hyperintensity and multifocal old infarcts (Fig. 4). The ASL sequence shows hypoperfusion at bilateral lateral temporal and parietal, bilateral occipital, and bilateral frontal regions (Fig. 5). Correlating with history of dementia, MRI findings could represent vascular dementia with underlying chronic small vessel disease (Fazekas 2) and multifocal old lacunar infarctions.Fig. 4 (A) MRI brain T1 (FLAIR): Generalized bilateral volume loss of gyri, moderate cerebral atrophy GCA-scale 2. (B) MRI brain FLAIR (Coronal oblique): Symmetrical widening of choroid fissure, MTA score 1. (C) MRI brain T2 (Axial): Beginning of white matter hyperintensities at bilateral frontal and parietal lobe with irregular periventricular white matter hypertensities (arrow), in keeping with Fazekas 2.

Fig 4

Fig. 5 MRI brain Fused ASL perfusion with FLAIR axial imaging reveals diffuse reduction in cerebral blood flow of the bilateral lateral temporal and parietal, bilateral occipital, and bilateral frontal regions.

Fig 5

Discussion

Neurocognitive disorders (NCD) are primarily diagnosed clinically. They involve multiple signs and symptoms that interfere with higher cortical functions such as memory, orientation, comprehension, and calculation. Gradually, these disorders impair and compromise the ability to perform independent daily tasks [2].

NCD can be classified anatomically and etiologically. The anatomical classification is based on the distribution of brain networks and categorizes dementia into cortical dementia and fronto-subcortical dementia. The etiological classification is divided into primary degenerative (idiopathic) and secondary dementia. Examples of primary causes include Alzheimer's disease, Lewy body dementia, and frontotemporal degeneration, while vascular dementia is a common secondary cause.

There are overlapping clinical features in neurocognitive disorders, making imaging crucial for guiding diagnosis. Perfusion, functional, and molecular imaging are helpful when the presentation is unclear. The initial role of MRI in dementia is to rule out treatable causes. FDG PET imaging is an established diagnostic marker for Alzheimer's disease. Recent studies have shown optimistic results, with cerebral blood flow in ASL MRI and hypometabolism in FDG PET showing consistent regional abnormalities [[2], [3]]. ASL MRI offers many benefits compared to FDG PET: it is more cost-effective, noninvasive, minimizes radiation exposure, and does not require an external tracer. The metabolism of glucose is intricately linked to brain perfusion, suggesting that regional blood flow and brain metabolism are influenced by localized decreases in neuronal function [[2], [3], [4]].

The reduction in cerebral blood flow in late-onset AD is possibly attributed to cerebrovascular disease, whereas young-onset AD often lacks significant cerebrovascular pathology. This allows for the assessment of cerebral blood flow (CBF) alterations specifically related to AD pathogenesis [4]. ROI-based cerebral blood flow analysis can distinguish between individuals with moderate cognitive impairment and those with AD. There is a high degree of concordance and consistency between ASL MRI and FDG PET [3]. ASL MRI offers superior sensitivity in detecting regional cerebral blood flow changes among mild cognitive impairment patients [5]. Reduced cerebral blood flow is observed in individuals with Type 2 diabetes mellitus and subjective cognitive decline (SCD), indicating a preclinical stage of dementia [6]. They are comparable findings in reducing cerebral blood flow in ASL with hypometabolism FDG PET in the Mild Cognitive subgroup [[7], [8]].

Previous studies have identified significant hypoperfusion on ASL imaging in the right inferior parietal cortex, extending to the bilateral posterior cingulate gyri, bilateral superior and middle frontal gyri, and the left inferior parietal lobe in AD. Compromised cerebral blood flow in small or large vessels can also be detected using MRI perfusion imaging. ASL offers additional insights into cerebral blood flow, which is 20% lower in individuals with diffuse confluent white matter hyperintensities (WMH) compared to those with punctiform or early confluent WMH. In mild cognitive impairment (MCI), hypoperfusion changes have been seen at the bilateral parietal lobes, posterior cingulate cortex, precuneus, left occipital lobe, and bilateral frontal and temporal lobes. Thus, different regional involvement of cerebral blood flow in neurocognitive disorders narrows the possible differential diagnosis [9].

Cerebrovascular risk factors for example hypertension, dyslipidemia, diabetes mellitus was identified as a risk to develop the vascular cognitive impairment. It has been identified as a significant risk factor for cerebrovascular pathology [10]. Hypoperfusion of the cerebral blood flow precede the clinical onset of vascular dementia.

Conventional neuroimaging is essential for diagnosing neurocognitive disorders. However, when there is overlapping or atypical clinical presentation observed, ASL MRI sequence has potential and promising aid in identifying the subtle perfusion changes. Therefore, early detection of cerebral hypoperfusion is important for individual who are at risk for cognitive impairment. Thus, prevention and early targeted treatment can be given to delay the onset of cognitive impairment.

Conclusion

In conclusion, neurocognitive disorders exhibit a variety of clinical presentations. Therefore, it can be challenging to diagnose, particularly when conventional neuroimaging only detects subtle changes. Cerebral blood flow with arterial spin labeling magnetic resonance has shown promising potential and as an alternative to FDG PET, in characterizing and diagnosis of neurocognitive disorders. Neurocognitive diseases can be prevented by identifying those at risk and providing them with early identification and appropriate treatment.

Patient consent

Verbal and written informed consent were obtained from the patient for inclusion in this case report.

Ethical approval

Research and ethics committee approval for this case report is not a requirement according to Medical Research and Ethics Committee and Institute of Clinical Research Malaysia.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments: The authors would like to express their deepest gratitude to all the staffs from Imaging unit of Universiti Sains Malaysia and to all those directly or indirectly involved in this case write up.

Financial support: There is no financial support received for the study.
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