Low Amyloid-β Deposition, Dopaminergic Activity Characterize MCI With Lewy Body Dementia

Kejal Kantarci, MD

Data from a recent study has suggested that the majority of patients with mild cognitive impairment (MCI) with elements of Lewy body dementia (DLB; MCI-LB) are characterized by low amyloid-β deposition and reduced dopaminergic activity. Amyloid-β positron emission tomography (PET) imaging and dopamine transporter imaging (I-FP-CIT SPECT) are useful in characterizing phenotypes of MCI-LB.

Patients with MCI and clinical features of DLB were grouped into β-amyloid A+ or A- and I-FP-CIT SPECT D+ or D- groups. Patients fell into 1 of 4 groups: A+D+, A+D-, A-D+, or A-D-. Researchers found that 38.2% (n = 13) of patients fell into the A-D+ biomarker profile, followed by 26.5% (n = 9) each in the A+D+ and A-D- groups, and 8.8% (n = 3) in the A+D- group. 

Senior author Kejal Kantarci, MD, researcher, Mayo Clinic, and colleagues wrote that “in this study that utilized amyloid-β PET and I-FP-CIT SPECT biomarkers in MCI-LB, we confirmed the presence, and in some, the co-existence of amyloid-β pathology and Lewy-related pathology.”

Kantarci and colleagues investigated 34 patients with MCI-LB, 30 (88.2%) of which were male. The patients had a mean Mini-Mental State Exam (MMSE) score of 27.6 (standard deviation [SD], 1.7) and a mean Clinical Dementia Rating scale Sum of Boxes (CDR-SB) score of 1,7 (SD, 0.8). Probable rapid eye movement sleep behavior disorder (REM RBD) was the most common core DLB feature observed in 94.1% of patients followed by parkinsonism in 70.6%, fluctuations in 41.2% and visual hallucinations (VH) in 14.7% of patients. About half of patients (47.1%) presented with 2 core DLB features, while 32.4% presented with 3 or more and 20.6% presented with 1 core feature.

READ MORE: Amyloid ß and Tau Pathology Linked to Dementia With Lewy Bodies Phenotype

Kantarci and colleagues found that patients with an A+ biomarker tended to be older with a higher frequency of APOE ε4 carriers and lower MMSE scores than the A- group. Patients with a D+ biomarker were less likely to have fluctuations than the D- group (P = .026), which remained significant after age adjustment, and were more likely to have RBD than those in the D- group (P = .048), which did not remain significant. The D+ subgroup also had higher Unified Parkinson Disease Rating Scale (UPDRS) 3 scores (P = .019).

The authors also found that lower putamen DaTQUANT z-scores (P <.001) and lower Pittsburgh compound B standard uptake value ratios (PiB SUVRs; P = .037) were independently associated with higher Unified Parkinson’s Disease Rating Scale (UPDRS) Part III scores.

They also analyzed associations between biomarkers and number of core features and found that 57.1% of patients with 1 core feature, 75% of patients with 2 core features, and 54.5% of patients with 3 or 4 core features were in the D+ group. The rate of A+ was 57.1% in patients with 1 core feature, 25% in patients with 2, and 36.4% in patients with 3 or 4 core features. No difference was observed in the global cortical PiB SUVRs or putamen DaTQUANT z-scores among the MCI-LB patients and the number of core DLB features.

“Patients with MCI who have core clinical features of DLB have imaging biomarker abnormalities that are associated with clinical phenotypes. I-FP-CIT SPECT biomarker positivity was associated with the core clinical features of DLB, suggesting that I-FP-CIT SPECT biomarker is a strong predictor of DLB at the prodromal stage. Association of A+ with worse cognitive function suggests that targeting amyloid-β deposition during the prodromal stage of DLB in a subset of patients who are A+ may be a potential strategy for slowing the progression from prodromal DLB to overt DLB,” Kantarci and colleagues concluded.

REFERENCE

Chen Q, Lowe VJ, Boeve BF, et al. Mild cognitive impairment at risk for Lewy body dementia. Neurology. Published online January 6, 2021. doi: 10.1212/WNL.0000000000011454