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Female gender, Head circumference, Alzheimer disease.

Gender difference in the prevalence and incidence of Alzheimer disease (AD) is well known , although debated . Female gender is an important risk factor for AD but the main cause of this is not known. An article by a Korean group of psychiatrists provides now the opportunity of rethinking some basic aspects of the anthropometry of the women that are possibly relevant for the development of AD, like head circumference and leg length. They studied 916 residents of a community in the South Korea, aged 65 or over, with a clinical screening method for detecting dementia and dementia subtypes, mainly Alzheimer’s disease, measuring also head circumference, leg length, apoE, and the social status. Women were 56,7 % of the non affected and 72,7% among the demented people. The authors found that smaller head circumference and shorter leg length were associated with poorer social condition in infancy, like coming from a rural area and to have a lower education. The anthropometric measures were independently associated with dementia, but only in women.
The author hypothesized that a poor condition in childhood could have affected height (limb length) and brain development, and that this was particularly true for women perhaps because of the preferential treatment of the male children in their culture.
Comment : The studies about the relationship between brain and head size and the development of dementia has a pretty long history, for its linkage to the “brain reserve theory” developed by Katzman . In this theory the onset of dementia is related to the brain (size) and cognitive reserve (education). The head circumference is well related to the brain volume, and both are smaller in women , so head size may be a “natural” predisposing factor for dementia in the female gender. But caution is needed when taking such conclusions. At first the findings of the Korean researchers must be considered: height and head size are strongly related, but are also independent factors for dementia and both may reflect a poorer childhood condition. Also lower education, a well known risk factor for dementia, may be due to the social condition and other data suggest an important correlation between head size and education. In particular data coming from the “Nun study” examined deeply this association, and found that it was strong in those who were destined to develop AD, those who carried apoE4 genotype and those who fulfilled neuropathologic criteria for AD. These findings are partially consistent with other studies that demonstrate an increased risk effect of the ApoE4 genotype in presence of smaller head circumference, with a younger age of onset of the disease . All these data may support the “brain reserve” theory: education for the cognitive reserve, apoE4 for the genetic reserve, head circumference for the brain/neurons reserve.
On the other hand we know that social condition can affect at least in part body size and education, and that female gender can sum up a smaller congenital size, a lower education and, at least in some developing countries, less nutrition in childhood, so to have a diminished brain reserve because of both biological and social conditions. These conditions might be a major contribution to the high presence of Alzheimer disease among women.


  1. Andersen K, Launer LJ, Dewy ME, et al. Gender differences in the incidence of AD and vascular dementia. The EURODEM Studies. Neurology 1999;53:1992–97.
  2. Edland SD, Rocca WA, Petersen RC, et al . Dementia and Alzheimer do not vary by sex in Rochester Minn. Arch Neurol 2002;59:1589–93.
  3. Katzman R, Terry R, De Teresa R et al Clinical, pathological, and neurochemical changes in dementia : a subgroup with preserved mental status and numerous neocortical plaques Ann Neurol 1988; 23 : 138 - 44
  4. Jorgensen JB, Paridon E, Quaade F The correlation between external cranial volume and brain volume Am J Phys Anthropol 1961; 19: 317 - 20
  5. Mortimer JA, Snowdon DA, Markesbery WR. Small head circumference is associated with less education in persons at risk forAlzheimer disease in later life. Alzheimer Dis Assoc Disord. 2008;22:249-54.
  6. Borenstein Graves A, Mortimer JA, Bowen JD, et al .Head circumference and incident Alzheimer's disease: modification by apolipoprotein E. Neurology. 2001 23;57:1453-60.