11 September 2001. One of the most pressing needs in Alzheimer's research today
is the ability to identify, among normal elderly people, those who will likely
go on to develop AD. A paper published today in the Proceedings of the National
Academy of Sciences brings researchers a step closer to attaining this goal, which
would make it possible to recruit presymptomatic patients into clinical trials
of experimental treatments before the disease has had time to kill large swaths
of neurons in their brains.
A team of scientists led by Mony de Leon at New York School of Medicine used
MRI-guided PET to image reductions in glucose metabolism in 48 cognitively normal
people over a period of three years. They wondered whether reduced glucose metabolism
in the entorhinal cortex (EC) would be able to predict subsequent hypometabolism
in other brain areas and cognitive decline. This hypothesis grew out of previous
work suggesting that AD pathology may start in the EC and then spread to the
hippocampus and temporal neocortex (Braak,
H. & Braak, E.), as well as other studies showing that layers 2 and 4 of
the EC already have lost 40 percent or 60 percent of their neurons, respectively, when
AD is barely diagnosable (Gomez-Isla
et al.) Previous imaging studies (Killiany
et al, Jack
et al, others) have managed to predict who will develop AD among people
with mild cognitive impairment (MCI), but not among normal subjects.
In this study, 12 of the 48 participants declined cognitively, 11 to MCI and
one to AD. Glucose hypometabolism in the entorhinal cortex that was detectable
at baseline accurately predicted this decline, the authors write. It also predicted
that a similar hypometabolic state would develop in the temporal lobe neocortex
and, less so, in the hippocampus. People heterozygous for the ApoE4 allele showed
a steeper metabolic decline in the lateral temporal lobe.
The authors conclude that a particular EC stage exists prior to diagnosable
AD, which can be detected in normal elderly people. By contrast, a more widespread
assortment of brain areas serve to predict progression to AD in people with
MCI. This again confirms the notion that EC changes precede damage in other
The authors caution, however, that their method is not widely applicable. It
is expensive, needs to be confirmed independently and in larger samples, and
cannot explain the mechanism underlying impaired glucose metabolism.-Gabrielle Strobel.
Reference:de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, Tsui W, Kandil E, Scherer AJ, Roche A, Imossi A, Thorn E, Bobinski M, Caraos C, Lesbre P, Schlyer D, Poirier J, Reisberg B, Fowler J.
Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). PNAS 2001 Sep 11;98(19):10966-10971. Abstract