Brief Communications
Total intracranial
volume: Normative
values and lack of
association with
Alzheimer’s disease
Abstract—A larger premorbid brain is hypothesized to provide neuronal
reserve against AD. Using MRI data from ongoing studies of normal aging
and AD, the authors tested this hypothesis. Mean total intracranial volume
was 15.8 cm3 smaller for cases among women (n 121 normal and 104 AD;
p 0.24) and 10.1 cm3 larger for cases among men (n 63 normal and 62
AD; p 0.59). These differences are small and nonsignificant, suggesting
that head size per se is not a critical determinant of AD.
NEUROLOGY 2002;59:272–274
S.D. Edland, PhD; Y. Xu, MD, PhD; M. Plevak, BS; P. O’Brien, PhD; E.G. Tangalos, MD;
R.C. Petersen, MD; and C.R. Jack, Jr., MD
Markers of the degenerative process in AD include
abnormal accumulations in the brain of extracellular
amyloid plaque, abnormal accumulations of intra-
neuronal paired helical filament tau, reduced brain
metabolism on PET, diminished cholinergic activity,
cell loss, and cerebral atrophy. Clinically, this degen-
erative process presents as a progressive decline in
memory performance and general cognitive function.
Although the relation between brain pathology and
clinical presentation of AD is not completely under-
stood, it is presumed that surviving, functional neu-
rons maintain what cognitive function remains in
patients with subclinical and clinically diagnosable
disease.
It has been suggested that reserve against the
clinical symptoms of disease could be provided by a
larger premorbid brain with larger neurons or a
larger number of neurons.1 Such a “neuronal re-
serve” could, arguably, prolong the subclinical stage
of disease and delay the onset of clinically diagnos-
able disease.
This hypothesis was based on the observed posi-
tive correlation between postmortem brain size and
antemortem cognitive performance in a sample of
nursing home residents followed longitudinally and
found at autopsy to have amyloid plaque pathology
consistent with AD.1 Brain weight