Alzheimer's disease (AD) is a slowly progressing form of dementia characterized in its earliest stages as a loss of memory. Individuals with amnestic mild cognitive impairment (aMCI) may be in the earliest stages of the disease and represent an opportunity to identify pathological changes related to the progression of AD. Synaptic loss is one of the hallmarks of AD and associated with cognitive impairment. The inferior temporal gyrus plays an important role in verbal fluency, a cognitive function affected early in the onset of AD. Unbiased stereology coupled with electron microscopy was used to quantify total synaptic numbers in lamina 3 of the inferior temporal gyrus from short postmortem autopsy tissue harvested from subjects who died at different cognitive stages during the progression of AD. Individuals with aMCI had significantly fewer synapses (36%) compared to individuals with no cognitive impairment. Individuals with AD showed a loss of synapses very similar to the aMCI cohort. Synaptic numbers correlated highly with Mini Mental State Examination scores and a test of category verbal fluency. These results demonstrate that the inferior temporal gyrus is affected during the prodromal stage of the disease and may underlie some of the early AD-related clinical dysfunctions.