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Letters to the Editor
May 2001

Premorbid Brain Volume and Dementia

Author Affiliations

Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001

Arch Neurol. 2001;58(5):831-833. doi:

In their recent article, Jenkins et al1 did not find total intracranial volume (TIV) to differ significantly between subjects with Alzheimer disease (AD) and controls, and therefore their results did not support a brain reserve hypothesis or the theory that larger premorbid size is protective against AD.

The brain reserve hypothesis is intriguing because, within a number of biological systems, size does relate to complexity or redundancy, and size often represents a protective factor against aging, injury, and/or disease.2,3 Brain size also relates to the complexity of cognitive tasks that can be performed by a given species,4 and in humans, brain size relates to psychometric intelligence.5,6 Premorbid intellectual ability may relate to dementia.7 Ultimate cranial capacity (the indirect measure for brain size) stabilizes by adolescence and occurs as a combination of genetic, biological, and environmental influences in utero and during infant and child development. Throughout this formative period, cranial capacity and brain size are relevant to outcome. For example, Stathis et al8 recently demonstrated that a smaller head circumference at age 8 months in low–birth-weight infants predicted a lower IQ score at age 6 years. Another study, by Martyn et al,9 demonstrated that a larger biparietal head diameter at birth correlated with measures of intelligence in adulthood. Also, Peterson et al10 have shown prematurity to be associated with reduced brain volume at 8 years of age, and this, in turn, was associated with poorer cognitive outcome. Since the hallmark signs of cognitive disintegration in AD commence with changes in memory, language, and executive function, and because such functions relate to quantitative changes in brain volume, it seems that there should be some relationship between factors associated with premorbid brain size and risk for AD.