Developing Topics.
| Publication Type | Case Report |
| Authors | Nordvig A, Fajardo A, Chiang G |
| Journal | Alzheimers Dement |
| Volume | 20 Suppl 8 |
| Issue | Suppl 8 |
| Pagination | e095803 |
| Date Published | 12/01/2024 |
| ISSN | 1552-5279 |
| Keywords | Alzheimer Disease, Magnetic Resonance Imaging |
| Abstract | BACKGROUND: Since lecanemab, an anti-amyloid monoclonal antibody targeting Aβ protofibrils, only modestly impacts cognition (27% slower cognitive decline over 18 months), tracking the effects on the brain in the early months is a clinical challenge. Serial noncontrast MRI scans are required by the FDA, to assess for the occurrence of amyloid-related imaging abnormalities (ARIA). Arterial spin-labeling MR (ASL-MR) is a 4-minute non-contrast easily-added sequence. Patterns of abnormal cerebral blood flow (CBF) on ASL-MR can correlate with neurodegenerative markers including FDG-PET. METHOD: Here we show CBF maps of two patients at baseline, and after receiving 4 infusions of lecanemab. Our figure is representative of six other patients in whom we have noted similar changes on therapy, and who will also be presented. RESULT: Figure 1 shows CBF maps of a man in his early seventies with mild cognitive impairment, due to AD. He had a family history of AD, and was diagnosed with a positive 18F-florbetaben PET and prescribed donepezil, with mild symptom improvement. His CSF markers were borderline (Abeta42 575 pg/mL, t-tau 289 pg/mL, p-tau 51 pg/mL, ATI 0.99.). Figure 2 shows CBF maps of a woman in her fifties, with a history of Crohn's disease, not currently requiring immunosuppression. She was diagnosed with posterior cortical atrophy due to AD, with a positive 18F-florbetaben PET and CSF compatible with AD (abeta42 366 pg/mL, t-tau 486 pg/mL, p-tau 72 pg/mL, ATI 0.45). She remained employed until a mild COVID infection, at which point her preexisting cognitive symptoms worsened (presumed longCOVID-related worsening). Both patients carried the ApoE e3/e3 genotype. In both cases, baseline low temporoparietal CBF increased at the scheduled MRI post-4th infusion. CONCLUSION: These cases show that CBF increases on lecanemab from baseline to after the 4th infusion. Preclinical investigations have demonstrated that it can protect neurons from Aβ-induced apoptosis, leading to neuronal viability and improved brain perfusion. CBF increases may also reflect increased synaptic activity after amyloid clearance and/or vascular changes, such as clearance of fibrinogen/amyloid clotting complexes. CBF has potential as a noninvasive and time-efficient marker of medication effect and perhaps efficacy over time. |
| DOI | 10.1002/alz.095803 |
| PubMed ID | 39783229 |
| PubMed Central ID | PMC11713404 |