28 February 2009

Hormone therapy linked to brain shrinkage, but not lesions

Hormone therapy, cognitive decline and dementia
Dementia News (Alzheimer’s Australia): 21 February 2008
The risks to women on hormone therapy have been the subject of research for some years. One long-term study is the Women's Health Initiative Memory Study (WHIMS), being conducted in the USA. Two papers arising from this research were published in this January’s issue of Neurology and both are reported on here.

The first paper, Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study, reports on research led by Dr Coker from Wake Forest University Health Sciences. Dr Coker and colleagues investigated whether cardiovascular disease underpins the dementia and cognitive decline that has been reported in women given hormone therapy (either conjugated equine oestrogen [CEE] on its own or CEE with medroxyprogesterone acetate [MPA]). The women in the study were between 71 and 89 years of age. Of those who had been taking part in the WHIMS trial, 1,403 had magnetic resonance imaging brain scans taken at various periods after stopping medication. The average time from the end of treatment at which brain scans were conducted on the women who had been taking the combination of CEE+MPA hormones was three years. The average time between ending treatment and having brain scans for those women who had been taking CEE alone was 1.4 years.

The researchers studied the women's brain scans to determine whether there was compromise to normal blood flow in the brain and whether this was attributable to hormone therapy. What they discovered was that compromise to blood flow in the brain was not associated with the hormone therapy these women had taken, but was related to age, smoking, history of cardiovascular disease, high blood pressure, global cognitive decline experienced since the trial had ended, and increased mild cognitive impairment or probable dementia that had been evident either during the trial or after the trial had ended.

The second paper, Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study, reports on research conducted by a team led by Dr Resnick from the Biomedical Laboratory of Personality and Cognition, Biomedical Research Center in Baltimore.

The team wanted to determine whether the brain scans from those women reported on above showed changes in brain volumes in any of various regions of the brain. They looked at total brain volume and then the volumes of the hippocampus (a part of the brain which is important in memory and spatial orientation), the frontal lobes (which have executive functions), and the ventricles (which produce cerebrospinal fluid, which cushions and protects the brain and spinal cord). They adjusted their findings to take into account the age of the women, the clinic sites they came from, and the estimated intracranial (part of the skull that houses the brain) volumes, as well as risk factors for dementia.

The results of these studies were that frontal lobe volume was lower among women who had been given hormone therapy; hippocampal volume was slightly lower; and differences in total brain volume approached statistical significance. These results held irrespective of whether women had been given CEE+MPA or CEE only. But the greatest loss of brain volume was seen in women who had been experiencing cognitive deficits before taking hormone therapy.

Taken together, these two sets of studies suggest that brain shrinkage, rather than compromise to blood flow, may underlie the increase in dementia and decrease in global cognitive functioning seen in women over 65 given hormone therapy.

Study references:

Coker LH, Hogan PE, Bryan NR, Kuller LH, Margolis KL, Bettermann K, Wallace RB, Lao Z, Freeman R, Stefanick ML, Shumaker SA. 2009. Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study. Neurology; 72(2):125-34.

Resnick SM, Espeland MA, Jaramillo SA, Hirsch C, Stefanick ML, Murray AM, Ockene J, Davatzikos C. 2009. Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study. Neurology; 72(2):135-42.

Also see Alzheimer’s News posting “Postmenopausal hormone therapy and regional brain volumes” (18 January 2009) for additional references and commentary.

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