Positron Emission Tomography Metabolic Correlates of Apathy in Alzheimer Disease

Abstract

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. Design: 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 (PϽ.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.

Neurobiology of apathy in Alzheimer's disease

“…lanctot and colleagues found similar results, showing decreased metabolism in left Acc and right oFc in Ad apathetic patients scanned with sPecT 60 . More recently, Marshall and colleagues, employing PeT in Ad patients with mild to moderate dementia, showed that apathy was related to hypometabolism in ventromedial PFc, including the ventral Acc and medial oFc 61 , as predicted and described below in our proposed account for neurobiology of apathy in Ad. PeT data from frontal variant of frontotemporal dementia (fvFTd) has also shown a significant relationship between apathy and oFc hypometabolism 62 .…”

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

“…1,2 Neuroimaging studies in neurodegenerative diseases have linked the state of cognitive inertia, characteristic of apathy, to decreased activity in a network that encompasses the dorsolateral prefrontal cortex, lateral aspects of the caudate nucleus and putamen, anterior cingulate cortex, and posterior parietal cortex. 33,[79][80][81][82] We have focused on Parkinson's disease as a model to study motivated behaviours, in which the symptoms of apathy are associated with defi cits in dopaminergic innervation from the mesolimbic and mesocortical pathways. Patients with Parkinson's disease who are exposed to non-physiological dopaminergic stimulation are at high risk of developing a range of behavioural addictions or impulse control disorders.…”

“…In Alzheimer's disease, the degree of apathy severity has been linked to neurofi brillary tangles and volume loss in the medial prefrontal cortex, including the anterior cingulate cortex. 76 Accordingly, other functional imaging studies [79][80][81][82] have shown an association between apathy and hypometabolism in the medial orbitofrontal cortex and anterior cingulate cortex.…”

Loss of gait control assessed by cognitive-motor dual-tasks: pros and cons in detecting people at risk of developing Alzheimer’s and Parkinson’s diseases

“…From a neuropathological point of view, dual-task-related gait changes in AD could reflect metabolic changes in cells of the associative cortices and hippocampal complex (Rolls and Grabenhorst 2008). The study of Marshall et al (2007) suggests that the reduction in glucose consumption and perfusion in the cingulate gyrus and orbitofrontal cortex may also explain the difficulty of patients with AD to perform dualtask walking.…”