Serial Nigrostriatal Dopaminergic Imaging in Mild Cognitive Impairment With Lewy Bodies, Alzheimer Disease, and Age-Matched Controls

Background and Objectives Progressive nigrostriatal pathway degeneration occurs in patients with dementia with Lewy bodies (DLB). Our objective was to investigate whether repeat 123[I]-FP-CIT SPECT can identify progressive dopaminergic loss in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB).

Methods Individuals with MCI-LB and MCI due to Alzheimer’s disease (MCI-AD) underwent comprehensive clinical assessment, 123[I]-FP-CIT SPECT at baseline and annual reviews, and baseline cardiac ¹²³I-MIBG. Mixed effects models were used to investigate changes in 123[I]-FP-CIT specific binding ratio (SBR) in the striatum for each diagnostic group compared with controls. The time interval to the development of a quantitatively abnormal 123[I]-FP-CIT SPECT in the possible and probable MCI-LB group was determined as the time it took for these groups to reach a striatal uptake two standard deviations below aged-matched controls. Test re-test variation was assessed using baseline and repeat scans in controls.

Results We recruited 20 individuals with MCI-AD, 11 with possible MCI-LB, 25 with probable MCI-LB and 29 age-matched controls. The mean time between baseline and final image was 1.6 years (SD = 0.9, range 1.0 to 4.3). The annual estimated change in SBR was 0.23 for controls (95% CI: -0.07 to 0.53), -0.09 (-0.55 to 0.36) for MCI-AD, -0.50 (-1.03 to 0.04) for possible MCI-LB and -0.48 (-0.89 to -0.06) for probable MCI-LB. The median annual percentage change in SBR in MCI-LB was -5.6% (95% CI: -8.2% to -2.9%); 2.1% (-3.5% to 8.0%) for MCI-AD. The extrapolated time for a normal scan to become abnormal was 6 years. Controls and MCI-AD showed no significant change in dopaminergic binding over time. The mean test-retest variation in controls was 12% (SD 5.5%), which cautions against over-interpretation of small changes on repeat scanning.

Discussion Progressive dopaminergic loss in the striatum is detectable using 123[I]-FP-CIT SPECT in MCI-LB at a group level. In clinical practice, individual change in striatal 123[I]-FP-CIT uptake appears to be of limited diagnostic value due to high test-retest variation.

Classification of Evidence This study provides Class II evidence that longitudinal declines in striatal uptake measured via 123[I]-FP-CIT SPECT are associated with mild cognitive impairment (MCI) due to Lewy body disease but not MCI due to Alzheimer disease.