Alzheimer’s Disease Neuropathologic Change in Cognitively Impaired Prostate Cancer Survivors
Bryan Neth1, Aivi Nguyen1, Aditya Raghunathan1, Eva Alden1, Umar Ghaffar1, Hugo Botha1, Vijay Ramanan1, Ronald Petersen1, Clifford Jack1, David Knopman1, Kathryn Ruddy1, Daniel Childs1, Jeffrey Karnes1, Jeffrey S Wefel2, Prashanthi Vemuri1, Jonathan Graff-Radford1
1Mayo Clinic, 2The University of Texas MD Anderson Cancer Center
Objective:
To determine if Alzheimer's disease neuropathic change (ADNC) is associated with androgen deprivation therapy (ADT) use in prostate cancer survivors with cognitive impairment.
Background:
ADT is an important treatment for the management of prostate cancer and has been associated with increased risk for cognitive impairment. The etiologic basis for ADT-related cognitive impairment is unknown.
Design/Methods:
We quantified ADNC (0-3; A: Thal amyloid phase, B: Braak neurofibrillary tangle stage, C: CERAD neuritc plaque score) in patients with pathologically confirmed diagnosis of prostate cancer from the Mayo Clinic Study of Aging. We collected details regarding oncologic care. We used t-test and Chi-square test to assess differences between continuous and categorical variables. We performed logistic regression corrected for age and APOE4-status to determine the association between ADT use and low (0-1)/high (2-3) ADNC.
Results:
Forty-six patients (mean 88 years at death, 48% APOE4 carriers) with history of prostate cancer (71 years at cancer diagnosis) and mild cognitive impairment or dementia with available neuropathology available were included. Thireteen (28%) patients received ADT (mean duration: 27 months). There were no demographic or other treatment differences by ADT status. However, patients who received ADT had higher PSA, Gleason score, more biochemical recurrences, and metastasis. Mean A (1.4 vs. 2.2, p=0.04), B (1.5 vs. 2.2, p=0.001), and C (1.3 vs. 2.2, p=0.007) scores were lower for patients who received ADT. Prior ADT use was associated with lower neurofibrillary tangle (OR: 0.08; 95% CI 0.01-0.43; p=0.0053) and neuritic plaque (OR: 0.09; 95% CI 0.03-0.46; p=0.0054) burden.
Conclusions:
Amongst cognitively impaired prostate cancer survivors there is less ADNC in those who received ADT, suggesting that in these patients, cognitive impairment may be attributable to factors related to ADT in addition to ADNC. Future analyses will focus on determining other contributors to cognitive impairment in patients with prostate cancer.
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