Positron emission tomography metabolic correlates of apathy in Alzheimer disease.
BACKGROUND
Apathy is the most common neuropsychiatric manifestation in Alzheimer disease (AD). Clinical, single-photon emission computed tomography, magnetic resonance imaging, and pathologic studies of apathy in AD have suggested an association with frontal dysfunction, most supportive of anterior cingulate abnormalities, but without a definitive localization.


OBJECTIVE
To examine the association between apathy and cortical metabolic rate on positron emission tomography in AD.


METHODS
Forty-one subjects with probable AD underwent [(18)F] fluorodeoxyglucose positron emission tomography imaging and neuropsychiatric and cognitive assessments. Global subscale scores from the Scale for the Assessment of Negative Symptoms in Alzheimer Disease were used to designate the absence or presence of clinically meaningful apathy. Whole-brain voxel-based analyses were performed using statistical parametric mapping (SPM2; Wellcome Department of Imaging Neuroscience, London, England), which yielded significance maps comparing the 2 groups.


RESULTS
Twenty-seven (66%) subjects did not have apathy, whereas 14 (34%) had apathy. Statistical parametric mapping analysis revealed significant reduced activity in the bilateral anterior cingulate region extending inferiorly to the medial orbitofrontal region (P < .001) and the bilateral medial thalamus (P = .04) in subjects with apathy. The results of the statistical parametric mapping analysis remained the same after individually covarying for the effects of global cognitive impairment, depressed mood, and education.


CONCLUSIONS
Apathy in AD is associated with reduced metabolic activity in the bilateral anterior cingulate gyrus and medial orbitofrontal cortex and may be associated with reduced activity in the medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating medial frontal dysfunction and related neuronal circuits in the neurobiology of apathy in AD and other neuropsychiatric diseases.
Marshall
Gad A
GA
Department of Neurology, University of California, Los Angeles, CA, USA.
Monserratt
Lorena
L
Harwood
Dylan
D
Mandelkern
Mark
M
Cummings
Jeffrey L
JL
Sultzer
David L
DL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
D019788:Fluorodeoxyglucose F18; D005947:Glucose