ADT–Dementia Link Refuted

A large patient cohort study suggests that use of androgen deprivation therapy does not increase the likelihood of developing dementia

medwireNews: Androgen deprivation therapy (ADT) does not increase the risk of dementia, analysis of a large UK patient cohort suggests.

The UK’s Clinical Practice Research Datalink included records for 30,903 men who received a new diagnosis of nonmetastatic prostate cancer between 1988 and 2015, say Laurent Azoulay, from the Jewish General Hospital in Montreal, Quebec, Canada, and co-workers.

In all, 58.2% of the prostate cancer patients received ADT, defined as receipt of gonadotropin-releasing hormone agonists, oral anti-androgen, oestrogens or bilateral orchiectomy.

Over an average of 4.3 years of follow-up, 799 men were diagnosed with dementia, giving an overall incidence of 6.0 cases per 1000 person–years. Over a third (36.7%) of these patients were diagnosed with Alzheimer’s disease and the remainder with other forms of dementia.

The incidence of dementia did not differ significantly between patients who underwent ADT and those who did not, at rates of 7.4 versus 4.4 cases per 1000 person–years, the researchers report in the Journal of Clinical Oncology.

This gave a non-significant hazard ratio of 1.02 for dementia with ADT use after adjusting for factors including age, alcohol-related disorders, smoking status and body mass index. Comorbidity, last recorded prostate-specific antigen level, head injury, and use of antidepressants and other psychiatric agents were also accounted for.

Secondary analysis also found no evidence to suggest that the risk of dementia was associated with duration of ADT use or with the use of any specific type of ADT. Nor were these two factors associated with the particular risk of developing Alzheimer’s disease or other forms of dementia.

Laurent Azoulay et al note that three earlier observational studies of ADT and risk of dementia had “conflicting findings”, with one indicating a significant increased risk and two suggesting a nonsignificant increased risk of dementia.

“Our study was specifically designed to circumvent the limitations of the previous studies”, the researchers write. For example, they chose a large population to give statistical power to detect an increased risk and adjusted for a range of potential confounders frequently overlooked in observational studies.

In addition, the team counted exposure to ADT only after a 1-year lag period to rule out inclusion of patients with a delayed diagnosis of dementia, reverse causality, detection bias and a minimal latency period between beginning ADT and onset of dementia.

Emphasising that the results “remained consistent” throughout a variety of sensitivity analyses accounting for potential sources of bias, the authors conclude: “The findings of this large population-based study indicate that the use of ADT is not associated with an increased risk of dementia either overall, by duration of use, or by type”.

But they add: “Additional studies in different settings are needed to confirm our findings.” 


Khosrow-Khavar F, Rej S, Yin H, et al. Androgen deprivation therapy and the risk of dementia in patients with prostate cancer. J Clin Oncol; Advance online publication 21 November 2016. DOI: 10.1200/JCO.2016.69.6203

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