In the Journals

ADT linked to Alzheimer’s disease, dementia among older men with prostate cancer

Elderly men with prostate cancer appeared more likely to be diagnosed with Alzheimer’s disease or dementia if treated with androgen deprivation therapy, according to study results published in JAMA Network Open.

“Studies using national samples have reported conflicting results regarding the diagnosis of Alzheimer’s disease or dementia among older patients with prostate cancer exposed to ADT,” Ravishankar Jayadevappa, PhD, research associate professor at Perelman School of Medicine at University of Pennsylvania, and colleagues wrote. “Limitations of these studies include inadequate adjustment for cancer stage, ADT dose and duration; reliance on single-institution data; lack of generalizability to the U.S. population; and measured and unmeasured bias associated with cohort studies. Clarifying the association between ADT and dementia could improve shared decision-making around the risks and benefits of ADT in prostate cancer.”

In the retrospective cohort study, Jayadevappa and colleagues used the SEER database to identify 154,089 older men diagnosed with prostate cancer between 1996 and 2003 and followed for at least 10 years after diagnosis (mean follow-up, 8.3 years; standard deviation [SD] = 4.7).

Among these men, 62,330 (mean age, 76 years; SD = 6) received ADT within 2 years of being diagnosed with prostate cancer, whereas 91,759 (mean age, 74.3 years; SD= 6) received no ADT.

The researchers conducted survival analyses to investigate the association between exposure to ADT and diagnosis of dementia and Alzheimer’s disease during follow-up. They also evaluated associations by ADT dose.

Results showed men exposed to ADT appeared more likely to be diagnosed with Alzheimer’s disease than men with no ADT exposure (13.1% vs. 9.4%; difference, 3.7%; 95% CI, 3.3-3.9; P < .001; HR = 1.14; 95% CI, 1.1-1.18). Researchers observed similar between ADT exposure and dementia (21.6% vs. 15.8%; difference, 5.8%; 95% CI, 5.4-6.2; P < .001; HR: 1.2; 95% CI, 1.17-1.24).

Propensity score-adjusted associations by ADT dose were as follows:

  • one to four doses: HR = 1.19; 95% CI, 1.15-1.24 for Alzheimer’s disease; HR = 1.19; 95% CI, 1.15-1.23 for dementia;
  • five to eight doses: HR = 1.28; 95% CI, 1.22-1.35 for Alzheimer’s disease; HR = 1.24. 95% CI, 1.19-1.29 for dementia; and
  • more than eight doses: HR = 1.24; 1.16-1.34 for Alzheimer’s disease; HR = 1.21; 95% CI, 1.15-1.28 for dementia.
  • The number needed to harm for Alzheimer’s disease was 18 patients (95% CI, 17-19) and for dementia was 10 patients (95% CI, 9.5-11).

Researchers acknowledged the potential lack of generalizability of the results, as the study included only fee-for-service Medicare enrollees aged 66 and older who lived in a SEER study region and did not participate in a health maintenance program.

Future studies should focus on understanding the possible biological mechanism of ADT treatment and dementia, according to the researchers.

“The list of effective ADT agents has recently grown with the addition of androgen synthesis inhibitors and second-generation antiandrogens,” they noted. “Furthermore, data are accumulating for the use of such agents earlier in the course of disease progression. Our results suggest that clinicians need to carefully weigh the long-term risks and benefits of exposure to ADT in patients with a prolonged life expectancy and stratify patients based on dementia risk prior to ADT initiation.” – by Jennifer Byrne

Disclosures: Jayadevappa reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

 

Elderly men with prostate cancer appeared more likely to be diagnosed with Alzheimer’s disease or dementia if treated with androgen deprivation therapy, according to study results published in JAMA Network Open.

“Studies using national samples have reported conflicting results regarding the diagnosis of Alzheimer’s disease or dementia among older patients with prostate cancer exposed to ADT,” Ravishankar Jayadevappa, PhD, research associate professor at Perelman School of Medicine at University of Pennsylvania, and colleagues wrote. “Limitations of these studies include inadequate adjustment for cancer stage, ADT dose and duration; reliance on single-institution data; lack of generalizability to the U.S. population; and measured and unmeasured bias associated with cohort studies. Clarifying the association between ADT and dementia could improve shared decision-making around the risks and benefits of ADT in prostate cancer.”

In the retrospective cohort study, Jayadevappa and colleagues used the SEER database to identify 154,089 older men diagnosed with prostate cancer between 1996 and 2003 and followed for at least 10 years after diagnosis (mean follow-up, 8.3 years; standard deviation [SD] = 4.7).

Among these men, 62,330 (mean age, 76 years; SD = 6) received ADT within 2 years of being diagnosed with prostate cancer, whereas 91,759 (mean age, 74.3 years; SD= 6) received no ADT.

The researchers conducted survival analyses to investigate the association between exposure to ADT and diagnosis of dementia and Alzheimer’s disease during follow-up. They also evaluated associations by ADT dose.

Results showed men exposed to ADT appeared more likely to be diagnosed with Alzheimer’s disease than men with no ADT exposure (13.1% vs. 9.4%; difference, 3.7%; 95% CI, 3.3-3.9; P < .001; HR = 1.14; 95% CI, 1.1-1.18). Researchers observed similar between ADT exposure and dementia (21.6% vs. 15.8%; difference, 5.8%; 95% CI, 5.4-6.2; P < .001; HR: 1.2; 95% CI, 1.17-1.24).

Propensity score-adjusted associations by ADT dose were as follows:

  • one to four doses: HR = 1.19; 95% CI, 1.15-1.24 for Alzheimer’s disease; HR = 1.19; 95% CI, 1.15-1.23 for dementia;
  • five to eight doses: HR = 1.28; 95% CI, 1.22-1.35 for Alzheimer’s disease; HR = 1.24. 95% CI, 1.19-1.29 for dementia; and
  • more than eight doses: HR = 1.24; 1.16-1.34 for Alzheimer’s disease; HR = 1.21; 95% CI, 1.15-1.28 for dementia.
  • The number needed to harm for Alzheimer’s disease was 18 patients (95% CI, 17-19) and for dementia was 10 patients (95% CI, 9.5-11).

Researchers acknowledged the potential lack of generalizability of the results, as the study included only fee-for-service Medicare enrollees aged 66 and older who lived in a SEER study region and did not participate in a health maintenance program.

Future studies should focus on understanding the possible biological mechanism of ADT treatment and dementia, according to the researchers.

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“The list of effective ADT agents has recently grown with the addition of androgen synthesis inhibitors and second-generation antiandrogens,” they noted. “Furthermore, data are accumulating for the use of such agents earlier in the course of disease progression. Our results suggest that clinicians need to carefully weigh the long-term risks and benefits of exposure to ADT in patients with a prolonged life expectancy and stratify patients based on dementia risk prior to ADT initiation.” – by Jennifer Byrne

Disclosures: Jayadevappa reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.