Low-Dose Whole Brain Radiation Therapy Elicits Positive Results in Early Alzheimer Disease Dementia
A presentation at CTAD 2021 included data from 5 patients enrolled in a phase 2a trial to evaluate neurocognitive, imaging, and safety outcomes of the therapeutic approach in early AD dementia.
C. Leland Rogers, MD
Data from a recent study show patients with early Alzheimer dementia (eAD) treated with low-dose whole brain radiation therapy (LD-WBRT) experienced stability to improvement in different areas of study. Findings were presented at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD), November 9-12.
A total of 5 patients with a clinical diagnosis of dementia that aligned with the NINCDS-ADRDA criteria for eAD were enrolled in the phase 2a trial—2 men and 3 women—with a median age of 73.2 years. Patients underwent evaluations to assess neurocognitive function (NCF), psychological function (PF), as well as quality of life (QOL).
According to a comparison of Mini-Mental State Examination–Second Edition T-scores prior to treatment and at 12 months, 3 patients improved, 1 remained stable, and 1 declined, following treatment with LD-WBRT. Naming, learning, and memory skills, which are anticipated to decline in eAD, remained stable in 4 patients at year 1, and 3 patients had trends for improved verbal learning. The sole patient who declined did so in these measures as well as Groove Pegboard and Semantic Fluency, and was also the oldest patient included, at 77 years.
Brief Visuospatial Memory Test-Revised (BVM T-R) learning and memory improved in 1 patient, and numeric improvements were seen in each patient from 9 to 12 months. Patients saw some decline in semantic fluency, which may suggest temporal lobe dysfunction, but assessments for processing speed (Grooved Pegboard, Wechsler Adult Intelligence Scale–Fourth Edition [WAIS-IV], Coding, Trailmaking A), attention (WAIS-IV Digit Span), visuospatial skills (Judgment of Line Orientation [JLO], BVM T-R Copy), executive functions (Trailmaking A+B, lexical fluency), mood (Patient Health Questionnaire-9, Generalized Anxiety Disorder–7-item), and QOL (Quality of Life in Alzheimer’s Disease scale, Quality of Life in Dementia scale, Everyday Cognition scale) all remained stable. Both patient-reported and informant-reported QOL remained stable in all 5 patients.
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Stability was seen in positron emission tomography (PET) scans. Investigators, led by C. Leland Rogers, MD, radiation oncologist, GammaWest Cancer Services, Jordan Valley Cancer Center, West Jordan, Utah, also noted the possibility for “modest improvements” in both hippocampal amyloid and parietotemporal fluorodeoxyglucose (FDG).
A screening physical exam, pre-treatment NCF, PF, and QOL assessments, as well as Florbetapir and FDG PET imaging, were required for all participants. Patients underwent LD-WBRT (2 Gy x 5) and were evaluated via physical exams and NCF, PF, and QOL assessments at 6 weeks, 3 months, 9 months, and 12 months (Boston Naming Test and JLO were only assessed at baseline and 12 months). FDG and Florbetapir PET were evaluated at 6 months and toxicities were assessed at each visit. Results were also reviewed by an independent Data Safety Monitoring Committee, with no safety issues encountered, aside from transient epilation.
“We are now seeking to open a phase 3 trial with randomization between observation and LD-WBRT,” Rogers et al wrote on the presentation poster. “Follow-up beyond 1 year will be required to determine whether improvements in several functional domains at 9 to 12 months and possible improvements in imaging are sustained.”
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