Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies

Abstract

Background Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. Aims To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. Method We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. Results At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3. Conclusions It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

Lack of evidence to support the conclusion that dopaminergic imaging is useful to diagnose mild cognitive impairment with Lewy bodies

“…We read with interest Roberts et al's paper on dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies (MCI-LB). 1 However, we believe that the authors’ conclusion that dopamine imaging is useful when Lewy body disease is suspected in a patient with MCI is not supported by the data presented. This otherwise well-designed and conducted study has issues that we commonly see in our Cochrane Dementia reviews of dementia tests.…”

Olfactory impairment in mild cognitive impairment with Lewy bodies and Alzheimer’s disease

“…As detailed previously (Donaghy et al, 2020;Roberts et al, 2021a;2021b), medically stable patients aged 60 years or older with a clinical diagnosis of MCI were recruited from local memory services in the North-East of England between April 2016 and September 2019. Potential study participants either reported the presence of any core clinical feature of DLB (complex visual hallucinations, rapid eye movement (REM) sleep behavior disorder, cognitive fluctuations, or parkinsonism not preceding cognitive impairment by more than 12 months), or any supportive clinical feature found in DLB, but not specific to this (e.g.…”

“…Following consent participants underwent a research-level assessment involving a semistructured interview, clinical and neurocognitive assessment and neurological examination by a medical doctor (RD ans SL), and imaging with FP-CIT, MIBG, and MRI (Firbank et al, 2021;Roberts et al, 2021a;2021b) at baseline, and then had longitudinal review at approximately annual follow-ups. Mean (SD) of maximum follow-up were 1.4 (0.98) years, with a maximum of 3.7 years from baseline.…”

“…A detailed neuropsychological evaluation was also carried out as reported previously (Donaghy et al, 2020) which included the ACE-R, a 100-point cognitive screening test from which MMSE score was derived. Dopaminergic 123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) single-photon emission computed tomography (FP-CIT) and cardiac MIBG imaging were offered to all participants as previously described (Roberts et al, 2021a;2021b). FP-CIT images were visually rated as normal or abnormal by a five-person panel of experienced image analysts, blind to clinical information.…”

“…We have reported the diagnostic utility of both dopaminergic imaging with 123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) (FP-CIT) and cardiac metaiodobenzylguanidine (MIBG) imaging in mild cognitive impairment (MCI). Both had high specificity (88% for each; Roberts et al, 2021a;2021b) but more modest sensitivity for identifying MCI with Lewy bodies (MCI-LB) compared with MCI-AD. There is therefore a need to find simple, inexpensive tests which can be applied in memory services, with the aim of identifying a large proportion of those with likely LB disease.…”