P1–433: PET metabolic correlates of apathy in Alzheimer's disease

Apathy is the most common behavioral manifestation in Alzheimer's disease (AD). Clinical studies, single photon emission computed tomography (SPECT) studies, and pathologic correlations of apathy in AD have shown an association with frontal dysfunction without a definitive localization. To examine the relationship between apathy and cortical metabolic rate on positron emission tomography (PET) in AD. 41 subjects with probable AD underwent FDG–PET imaging, and behavioral and cognitive assessments. The Scale for the Assessment of Negative Symptoms in Alzheimer's Disease (SANS–AD) was administered to all subjects. Two groups were designated based on absence or presence of clinically meaningful apathy derived from SANS–AD global subscale scores. Subjects who had questionable or no avolition/apathy and social/emotional withdrawal were designated as not having apathy, while subjects who had mild–severe avolition/apathy or social/emotional withdrawal were designated as having apathy. Whole–brain voxel–wise analyses were performed using statistical parametric mapping (SPM2), yielding significance maps comparing the two groups. 27 subjects did not have apathy, while 14 subjects had apathy. Mean age was 75.3±8.2 years, cognitive symptom duration 2.7±2.3 years, education 13.7±3.8 years, gender (88% male, 12% female), and Mini–Mental State Examination (MMSE) 19.6±6.1. SPM analysis revealed significant hypometabolism in the bilateral anterior cingulate region extending inferiorly to the medial orbitofrontal region (cluster level p<0.001), as well as in the bilateral medial thalamus (p=0.042) in subjects with apathy. Subjects with apathy had lower MMSE scores when compared to subjects without apathy (16.8±5.0 vs. 21.1±6.2, respectively, t=2.24, p=0.031). The results of the SPM analysis remained the same after co–varying for the effect of MMSE score on metabolic rate. Apathy in AD is associated with bilateral anterior cingulate, medial orbitofrontal, and medial thalamic hypometabolism. This is one of the few PET studies to address apathy in AD, and these results reinforce the confluence of evidence from other investigational modalities in implicating medial frontal dysfunction in the neurobiology of apathy in AD and other neuropsychiatric diseases.