Relevance of ¹²³I-FP-CIT SPECT brain scans in routine clinical settings

The findings from Walker et al's study ¹ do not come as a surprise. The high sensitivity and specificity of ¹²³I-ioflupane injection (¹²³I-FP-CIT) single photon emission computed tomography (SPECT) in diagnosing dementia with Lewy bodies (DLB) relate to a highly selected group of individuals, where underlying vascular pathology, severe mental and physical illness (including delirium) as well as medication interference were excluded. The working group also based their findings on a large group of patients with DLB, in comparison to rather modest size groups previously reported.

How relevant is this study to those of us working in a routine clinical setting? What is the sensitivity and specificity of the ¹²³I-FP-CIT SPECT brain scan in differentiating DLB from other dementia syndromes – and pseudodementia in our patients with more advanced age – with polypharmacy, polycomorbidity or recovering from a prolonged spell of acute confusion? Our own clinical experience working with older people with mental and medical health problems suggests that patients can be easily misdiagnosed as having DLB based on their ¹²³I-FP-CIT SPECT scans, and this includes individuals with major depression, severe brain trauma accompanied by widespread vascular white matter changes and small vessel disease, HIV encephalopathy, and even an older adult with mild intellectual disability with frontal lobe syndrome and extensive hypoperfusion as demonstrated on the SPECT brain scan. This is another confirmation of the clinician's gullibility when faced with ¹²³I-FP-CIT SPECT altered scans, as confirmed by Walker et al. ¹

With the availability of ¹²³I-FP-CIT SPECT scans, it is unclear what we have learned from the use of this imaging technique: do we use them for DLB diagnosis – based on their abnormal findings alone – or do we put them in the wider context of our patients' clinical symptomatology and medical history? There is a well-documented inverse relationship between vascular lesions and Lewy body pathology; ² 30% of patients with frontotemporal lobe dementia have abnormal scans and a significant reduction in uptake in the putamen and the caudate ³ (also highlighted by Walker et al ¹ ). About 5% of people diagnosed with DLB in fact have vascular dementia ⁴ and altered suspected ¹²³I-FP-CIT SPECT are also found in Creutzfeldt–Jakob disease. ⁵ It is of note that the influence of antipsychotic ⁶ and antidepressant medication ⁷ in older adults has largely been neglected in research studies in the public domain. The evidence from a limited number of animal ⁸ and human ⁹ studies clearly indicates that medication (e.g. haloperidol, citalopram, sertraline) reduces ¹²³I-FP-CIT dopamine binding to the dopaminergic transporter. However, there is an overwhelming lack of evidence for the most frequently used drugs in the older population, including a number of dopaminergic antagonists, the influence of polypharmacy, the effect of chronic administration of these drugs and modifying effects of advanced age. Until such data are available, it is not surprising that clinicians would be inclined to diagnose and/or accept the diagnosis of DLB based on the evidence of a dopaminergic abnormality. Even in their strictly controlled study, Walker et al ¹ report 5.4% mismatch between ¹²³I-FP-CIT SPECT scan findings and clinical DLB diagnosis. It is now the responsibility of the DLB research community to provide us with further clarification of clinical situations and exclusion criteria when using ¹²³I-FP-CIT SPECT scans to diagnose DLB in busy clinical settings.