About Cognitive Decline

On August 15, 2010, in Health Articles, by admin

The Cache County Study confirms previous observational studies, and accurately predicts the results of WHIMS when the age of HT initiation is comparable. This becomes a critical issue in reconciling the results of WHIMS with other observational studies in which the larger and more recent studies consistently demonstrate a reduction in the risk of AD or dementia by 30% to 80%. To simply dismiss these studies as being flawed by selection biases inherent in observational studies is nai”ve, and impedes the advancement of our understanding of the complexity of hormone action on the brain.

In typical observational studies, the majority of women would have initiated HT at the time of the menopause; relatively few would have initiated HT after the age of 65 years. However, the inclusion of both past and current users underestimates the magnitude of the effect of past use, as illustrated in the Cache County Study. In two studies that excluded past users, HT was found not to reduce the risk of dementia. There is a growing appreciation for the concept of a relatively limited window of opportunity for HT to significantly affect both the age-related decline in cognitive function and the progression and expression of AD. This concept has been ably articulated in recent reviews. Women with past but not current use of HT experienced a slowing of their rate of decline in cognitive function when assessed in their 70s. This difference cannot be explained by the duration of exposure to HT. Duration of use in past users was 5.2 years, one-third the duration of current users. However, past users initiated HT at an average age of 49 years, whereas current users initiated HT at an average age of 52 years. Thus, past users were more likely to have initiated HT at the time of the menopause, 20 to 30 years before the assessment of their rate of cognitive decline. A similar phenomenon is suggested by the study of Tang in which women who had used HT for less than 1 year appeared to have a 40% reduction in their risk of dementia at age 85 years. The authors note that most of these women had initiated HT at the time of the menopause.

The results of WHIMS provide some insight as to potential mechanism for these adverse effects on the expression of AD and dementia. Reminiscent of the effects of HT on cardiovascular disease, the incidence of Mild Cognitive Impairment (MCI), the precursor to dementia, peaked in the 2nd year of follow-up and then declined so that the incidence of MCI was greater in the placebo group in the 4th and 5th year of follow-up. The incidence of dementia peaked later but also declined in the 5th year in women on HT relative to women on placebo. This pattern suggests that HT triggers the progression of preclinical dementia to dementia in a relatively small, vulnerable population of women. In AD, the pathologic process is believed to be evident in the brain at least 5 to 10 years prior to the clinical manifestations of the disease. Thus, HT could not have initiated the underlying pathology of dementia observed in WHIMS. The exception would be dementia secondary to stroke. Although there was a 31% increase in the relative risk of stroke, exclusion of these few cases did not change the significance of the increase in dementias associated with HT. Furthermore, HT had a significant beneficial effect on cognitive function in women at risk for vascular dementia, consistent with an earlier clinical trial. The decline in the MCI over the last 2 years of observation raises the intriguing possibility that continuing HT may have either a null effect or even a beneficial effect on dementia. In the Cache County Study, more than 10 years of current HT had a null effect on dementia incidence.

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