Dementia Risk Factors Diverge by Gender

By Crystal Phend
4 may 2008-- Men with mild cognitive impairment tend to take a different fork in the road than women on the way to progression to dementia, researchers here found.Stroke conferred almost three-fold risk of dementia progression as one of the strongest predictive factors among men but had no prognostic value for women, reported Karen Ritchie, Ph.D., of the Université de Montpellier and La Colombière Hospital here, and colleagues, online in the Journal of Neurology, Neurosurgery, and Psychiatry. Major factors in progression to Alzheimer's and other types of dementia for women but not men included subclinical depression and use of anticholinergic drugs, according to the prospective population-based study of brain aging.
Because preventable risk factors differed between the sexes, the findings might have implications for practice, the researchers said.
"Intervention programs should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women," they wrote.
Most previous studies have adjusted for sex when determining risk factors for cognitive impairment but not considered that risk profiles may not be the same for men and women, Dr. Ritchie and colleagues said.
So the researchers analyzed four-year follow-up data from the Three City Study of men and women age 65 years and older randomly selected from the community-dwelling French populations in Bordeaux, Dijon, and Montpellier.
The analysis included 6,892 participants without dementia (mean age 74) who completed a baseline interview at a study center, or in their own homes if disabled, and were followed up every two years.
Overall, 42% of patients were classified as having mild cognitive impairment at baseline. During four years of follow-up, 6.6% of patients went on to be diagnosed with dementia, predominantly Alzheimer's disease (122 of 189 patients). Other dementia cases included 19 patients with vascular dementia and four with Lewy body dementia.
Another 37% of patients returned to normal cognitive functioning.
Women in the study were less likely than men to return to normal cognition (36% versus 39%) but also slightly less likely to progress from mild cognitive impairment to dementia (6% versus 8%).
Risk factors largely varied between men and women for both mild cognitive impairment and progression to dementia.
For both genders, mild cognitive impairment was more common among participants with depressive symptoms and use of anticholinergic medications. Other factors in mild cognitive impairment for men were older age, higher body mass index, and diabetes or stroke. For women, the factors were disability, social isolation, insomnia, and self-rated poor health.
Although not a factor in early impairment, the ApoE4 genotype associated with dementia in previous studies was the single strongest predictor of progression to dementia for men in the Three Cities Study (odds ratio 3.2, 95% confidence interval 1.7 to 5.7).
The ApoE4 allele was likewise a strong risk factor for progression among women (OR 2.3, 95% CI 1.4 to 4.0), but the best predictor of progression for them was loss of ability to perform daily tasks independently (OR 3.5, 95% CI 2.1 to 5.9).
Other main factors for progression to dementia rather than stable cognitive impairment or return to normal function for men were:
Stroke (OR 2.8, 95% CI 1.2 to 6.9)
Low level of education (OR 2.3, 95% CI 1.3 to 4.1)
Loss of ability to perform activities of daily living without assistance (OR 2.2, 95% CI 1.1 to 4.5)
Older age (OR 1.2, 95% CI 1.1 to 1.2)
For women, significant factors in dementia progression included:
Low level of education (OR 2.2, 95% CI 1.3 to 3.6)
Subclinical depression with symptoms but not diagnosis of major depression (OR 2.0, 95% CI 1.1 to 3.6)
Use of anticholinergic drugs (OR 1.8, 95% CI 1.0 to 3.0)
Older age (OR 1.1, 95% CI 1.1 to 1.2)
These differences between the sexes were not due to varying prevalence of these conditions in men and women, Dr. Ritchie and colleagues said.
Rather, "these findings support the notion that mild cognitive impairment is a common end point to multiple etiological pathways, which are not the same for men and women," they said.
The explanation could be different endocrinological risk factors and exposures to environmental hazards, such as life events, diet, and injury, they said.
However, the researchers noted that the study could have been limited by the duration of follow-up, which might have been too short for slowly evolving cases of dementia, and lack of analysis by domain-specific mild cognitive impairment.
The Three City Study was conducted under a partnership agreement between Inserm, the Victor Segalen--Bordeaux II University, and Sanofi-Synthelabo. The first phase of the study was funded by the Fondation pour la Recherche Médicale. The study was also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, the Institut de la Longévite´, Agence Française de Sécurité Sanitaire des Produits de Santé, the regional governments of the areas where the study was conducted, and the Fondation de France. The Lille Génopôle received an unconditional grant from Eisai.
The researchers reported no conflicts of interest.

Primary source: Journal of Neurology Neurosurgery and PsychiatrySource reference:Artero S, et al "Risk profiles for mild cognitive impairment and progression to dementia are gender specific" Neurol Neurosurg Psychiatry 2008; DOI: 10.1136/jnnp.2007.136903.