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. 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 (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.     

Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease

Few studies evaluate neuropathological correlates of behavioral changes in Alzheimer disease (AD). We identified 31 autopsy patients with a diagnosis of definite AD. Behavioral changes were assessed with the Neuropsychiatric Inventory. Brain sections were collected from bilateral orbitofrontal and left anterior cingulate, superior temporal, inferior parietal, occipital, and hippocampal cortices for quantification of neurofibrillary tangles (NFTs) and diffuse and neuritic plaques. Sections from frontal, cingulate, and hippocampal cortices were reviewed for the presence of Lewy bodies (LBs). Hypothesis-driven correlational analyses were performed by the bootstrap method. Subgroup analyses contrasted a group with high scores of one specific behavior to a group with low scores after equating groups for other behaviors. NFT burden in the left orbitofrontal cortex across all 31 patients significantly correlated with agitation scores (r = 0.41, p < 0.015) and NFTs correlated significantly (r = 0.66, p = 0.004) with higher agitation scores in the subgroup analysis. Left anterior cingulate NFTs, although not within our hypotheses, also showed a significant relationship to agitation within the subgroups (r = 0.76, p = 0.0003; Bonferroni p = 0.02). Seven patients, including three in the agitation subgroup, had cortical LBs. Aberrant motor behavior and NFT density in the left orbitofrontal cortex showed a significant relationship for the entire group (r = 0.38, p < 0.03) and for subgroups (r = 0.49, p = 0.04), whereas apathy and left anterior cingulate NFTs showed a significant relationship only for the entire group (r = 0.25, p < or = 0.01). These observations suggest that agitation and aberrant motor behavior are correlates of greater NFT pathology in the orbitofrontal cortex in AD, whereas increasing apathy may relate to greater NFT burden in the anterior cingulate.     

Neuroanatomical correlates of apathy in Parkinson's disease: A magnetic resonance imaging study using voxel‐based morphometry

Apathy is generally defined as a disorder of motivation and is considered one of the most common neuropsychiatric disturbances in Parkinson's disease (PD). Only few studies addressed the neuroanatomical correlates of apathy in PD. The aim of this article was to determine the structural correlates of apathy in PD patients. Fifty‐five PD patients underwent a neuropsychiatric and neuropsychological examination, and a 3 T magnetic resonance imaging scan was acquired. A voxel‐based multiple regression analysis was used to calculate correlation between gray matter density and severity measures of apathy. Apathy correlates with decreased cognitive functioning and more depressive symptoms but not with more severe motor symptoms. High apathy scores were correlated with low gray matter density values in a number of cortical brain areas: the bilateral precentral gyrus (BA 4, 6), the bilateral inferior parietal gyrus (BA 40), the bilateral inferior frontal gyrus (BA 44, 47), the bilateral insula (BA 13), the right (posterior) cingulate gyrus (BA 24, 30, 31), and the right precuneus (BA 31). Apathy in PD correlates with reduced gray matter density in a number of brain regions. The involvement of the cingulate gyrus and inferior frontal gyrus is in line with the results of earlier studies addressing apathy in patients with Alzheimer's disease or depressive disorder. Further studies addressing the pathogenesis of apathy are needed. © 2010 Movement Disorder Society.     

Neuropathologic correlates of apathy in Alzheimer's disease

Apathy is the most commonly observed behavioral disturbance in Alzheimer's disease (AD) and has been suggested to be frontally mediated. Neuritic plaque (NP) and neurofibrillary tangle (NFT) counts were performed for 8 brain regions in 29 subjects with definite AD. Neuropsychiatric Inventory (NPI) for autopsied subjects was obtained from questioning of caregivers of subjects included in the study. Chronic apathy and total NPI composite scores correlated with anterior cingulate NFT counts (r = 0.518, p = 0.01, and r = 0.438, p = 0.032). This analysis suggests that chronic apathy in AD correlates with a greater anterior cingulate NFT burden and that chronic behavioral changes are more reflective than acute changes of disease pathology.     

A SPECT study of apathy in Alzheimer's disease

BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.     

Regional cerebral blood flow abnormalities associated with apathy and depression in Alzheimer disease

The aim of this study was to identify brain areas related to apathy or depression in patients with Alzheimer disease (AD). Eighty-one AD patients were enrolled in this prospective study. (99m)Tc-HMPAO single photon emission computed tomography was performed to evaluate regional cerebral blood flow (rCBF). According to the Neuropsychiatric Inventory subscores of apathy and depression, 9 patients were classified as clinically significant (cs) depressed and non-cs-apathetic (D+) groups and 9 were classified as cs-apathetic and non-cs-depressed (A+) groups. In addition, 18 patients were classified as age-matched and Mini-Mental State Examination-matched disease control groups (D-, A-). The significance of rCBF differences between groups and the correlation between rCBF and subscores in 81 AD patients were estimated by SPM (uncorrected P < 0.005) analysis. D+ patients had significantly lower perfusion in the right orbitofrontal and inferior frontal gyri than D- patients, whereas A+ patients had this in the right amygdala, temporal, posterior cingulate, right superior frontal, postcentral, and left superior temporal gyri than A- patients. The negatively correlated areas with depression subscores included the left inferior frontal and the right middle frontal gyri and those with apathy subscores included the right temporal and right medial frontal gyri. We suggest that this finding may indicate that apathy and depression in AD patients involve distinct functional circuits.     

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Objectives

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with ¹⁸F fluorodeoxyglucose (FDG‐PET).

Methods

Forty‐two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG‐PET brain scan to provide data for voxel‐based morphometric analysis.

Results

Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self‐awareness in comparison with AD sample. Additionally, FDG‐PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD.

Conclusions

These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG‐PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd.     

Cortical brain metabolism as measured by proton spectroscopy is related to memory performance in patients with amnestic mild cognitive impairment and Alzheimer's disease

AIMS: To investigate the relationship between verbal memory performance and brain metabolism as determined by proton spectroscopy ((1)H-MRS) in selected cortical brain regions. To characterize metabolite abnormalities across the continuum of degenerative disease from mild impairment to dementia. METHODS: 27 controls, 27 amnestic mild cognitive impairment (aMCI) patients and 35 Alzheimer's disease (AD) patients. Verbal memory was assessed with the Text Memory Test, the Wordlist Learning Test (WL-Learning Test), and with a memory screening test, the Memory Alteration Test (M@T). Single-voxel (1)H-MRS was obtained in the posterior cingulate (P-CING), left temporal pole (L-TPOLE) and left posterior temporoparietal region (L-TPAR). RESULTS: WL-Learning Test scores were inversely associated with myoinositol/creatine ratios (mI/Cr) in the L-TPAR (r = -0.404, p < 0.002). Negative associations were also observed between M@T global scores and mI/Cr in the P-CING (r = -0.42; p < 0.001), L-TPOLE (r = -0.34; p < 0.005) and L-TPAR (r = -0.46; p < 0.001). A positive association was found between M@T scores and N-acetylaspartate concentrations in the P-CING (r = 0.33; p < 0.003). CONCLUSION: Verbal learning performance is related to metabolic changes in cortical brain regions known to be involved in the neurodegenerative process of aMCI and AD.     

Cortical thinning in subcortical vascular dementia with negative (11)C-PiB PET

To determine the existence of cortical thinning in subcortical vascular dementia (SVaD) with a negative 11C-Pittsburgh compound B (PiB) positron emission tomography scan and to compare the topography of cortical thinning between PiB-negative SVaD and Alzheimer's disease (AD), we enrolled 24 patients with PiB(-) SVaD, 81 clinically probable AD individuals, and 72 normal cognitive controls. Compared with controls, cortical thinning in PiB(-) SVaD was most profound in the perisylvian area, medial prefrontal area, and posterior cingulate gyri, while the precuneus and medial temporal lobes were relatively spared. When the cortical thickness of AD and PiB(-) SVaD were directly compared, PiB(-) SVaD demonstrated significant cortical thinning in the bilateral inferior frontal, superior temporal gyri, and right medial frontal and orbitofrontal lobes, while AD showed significant cortical thinning in the right medial temporal region. SVaD without amyloid burden may lead to substantial cortical atrophy. Moreover, characteristic topography of cortical thinning in PiB(-) SVaD suggests different mechanisms of cortical thinning in PiB(-) SVaD and AD.     

Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer's disease

Degeneration of cholinergic nucleus basalis (NB) cortical projection neurons is associated with cognitive decline in late-stage Alzheimer's disease (AD). NB neuron survival is dependent on coexpression of the nerve growth factor (NGF) receptors p75(NTR) and TrkA, which bind NGF in cortical projection sites. We have shown previously a significant reduction of NB perikarya expressing p75(NTR) and TrkA protein during the early stages of AD. Whether there is a concomitant reduction in cortical levels of these receptors during the progression of AD is unknown. p75(NTR) and TrkA protein was evaluated by quantitative immunoblotting in five cortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual cortex) of individuals clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Cortical p75(NTR) levels were stable across the diagnostic groups. In contrast, TrkA levels were reduced approximately 50% in mild/moderate and severe AD compared with NCI and MCI in all regions except visual cortex. Mini-Mental Status Examination scores correlated with TrkA levels in anterior cingulate, superior frontal, and superior temporal cortex. The selective reduction of cortical TrkA levels relative to p75(NTR) may have important consequences for cholinergic NB function during the transition from MCI to AD.     

Neuropsychiatric symptoms, functional impairment and executive ability in Thai patients with Alzheimer's disease

BACKGROUND: Instrumental activities of daily living (IADL) depend on executive planning and procedural memory mediated by the frontal lobes. Planning and judgment are involved in clock drawing. Neuropsychiatric symptoms are also mediated by frontal lobes, and a relationship between ADL, clock drawing and neuropsychiatric symptoms was hypothesized. OBJECTIVE: To investigate the relationship between behavioral disturbances, ADL, and executive function. METHODS: Seventy-three Thai patients with Alzheimer's disease (AD) were evaluated. Neuropsychiatric symptoms and behaviors were assessed with the Nevropsychiatric Inventory (NPI). The Thai version of the Mini-mental State Examination (TMSE) was utilized as a global cognitive assessment. A clock-drawing test (CDT) and both category (animals) and letter (ko, so in Thai) verbal fluency were used as executive measures. Thai ADL scale, Barthel Index (BI), and Functional Assessment Questionnaire (FAQ) were ADL measures used in this study. RESULTS: There were statistically significant correlations between CDT and the frontally-mediated behaviors of agitation (r = -0.367), apathy (r = -0.273) and disinhibition (r = -0.247). Verbal fluency correlated with agitation (r = -0.341). There were significant correlations between Thai ADL scores and agitation (r = 0.350), apathy (r = 0.441), and disinhibition (r = 0.417). FAQ correlated with the same three behaviors. After controlling for TMSE, a significant correlation remained between Thai ADL scores and agitation (r = 0.291) and apathy (r = 0.342). CONCLUSIONS: We demonstrated correlations between ADL and behavioral changes in Thai elderly with AD. Our results emphasize the important relationships among behavioral changes and impaired ADL.     

Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy

BACKGROUND: Functional imaging studies of major depressive disorder demonstrate response-specific regional changes following various modes of antidepressant treatment. OBJECTIVE: To examine changes associated with cognitive behavior therapy (CBT). METHODS: Brain changes underlying response to CBT were examined using resting-state fluorine-18-labeled deoxyglucose positron emission tomography. Seventeen unmedicated, unipolar depressed outpatients (mean +/- SD age, 41 +/- 9 years; mean +/- SD initial 17-item Hamilton Depression Rating Scale score, 20 +/- 3) were scanned before and after a 15- to 20-session course of outpatient CBT. Whole-brain, voxel-based methods were used to assess response-specific CBT effects. A post hoc comparison to an independent group of 13 paroxetine-treated responders was also performed to interpret the specificity of identified CBT effects. RESULTS: A full course of CBT resulted in significant clinical improvement in the 14 study completers (mean +/- SD posttreatment Hamilton Depression Rating Scale score of 6.7 +/- 4). Treatment response was associated with significant metabolic changes: increases in hippocampus and dorsal cingulate (Brodmann area [BA] 24) and decreases in dorsal (BA 9/46), ventral (BA 47/11), and medial (BA 9/10/11) frontal cortex. This pattern is distinct from that seen with paroxetine-facilitated clinical recovery where prefrontal increases and hippocampal and subgenual cingulate decreases were seen. CONCLUSIONS: Like other antidepressant treatments, CBT seems to affect clinical recovery by modulating the functioning of specific sites in limbic and cortical regions. Unique directional changes in frontal cortex, cingulate, and hippocampus with CBT relative to paroxetine may reflect modality-specific effects with implications for understanding mechanisms underlying different treatment strategies.     

Neuropsychological correlates of apathy and depression in patients with dementia

OBJECTIVE: To investigate the association between apathy and depression, and specific cognitive deficits in AD. BACKGROUND: Apathy and depression are frequent behavioral disorders in patients with AD. However, the neuropsychological correlates of these disorders have rarely been examined. METHODS: A comprehensive neuropsychological and psychiatric evaluation was carried out in 72 patients with AD with apathy and depression, 29 patients with AD with apathy only, 31 patients with AD with depression only, and 52 patients with AD with neither apathy nor depression (control group). RESULTS: Patients with apathy had significantly lower scores on tests of verbal memory, naming, set shifting, and verbal fluency compared with patients without apathy. The association of depression and apathy produced significantly more severe deficits compared with apathy only on a test of abstract thinking. Finally, depression in the absence of apathy was not associated with more severe cognitive impairments compared with the AD control group. CONCLUSIONS: Apathy, but not depression, is associated with significantly more severe frontal lobe related cognitive deficits in AD.     

Relationship between delusions and regional cerebral blood flow in Alzheimer's disease

To investigate the association between delusions and cerebral functional deficits in Alzheimer's disease (AD), we evaluated probable AD patients with and without delusions. METHODS: Functional brain imaging was performed by single photon emission computed tomography with technetium-99m-labeled ethyl cysteinate dimer (99mTc-ECD) in 64 AD patients and 76 age-matched normal healthy volunteers. SPECT data were analyzed by statistical parametric mapping. RESULTS: In AD patients, no differences were found in age and cognitive activities between those with (n = 25) and without (n = 39) delusions. Compared with normal healthy volunteers, AD patients had significantly decreased perfusion in the posterior cingulate gyri, precunei, and parietal association cortex. Moreover, in the patients with delusions, perfusion was significantly decreased in the frontal lobe with right side dominance. In the comparison between the patients with and without delusions, the patients with delusions had significantly decreased perfusion in the prefrontal cortex, anterior cingulate gyri, inferior to middle temporal cortices, and parietal cortex of the right hemisphere (p < 0.01). CONCLUSION: The functional deficits in the right hemisphere may be the cause of delusions in AD.     

Acupuncture at the Taixi （KI3） acupoint activates cerebral neurons in elderly patients with mild cognitive impairment

Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.     

Effect of age on regional cerebral blood flow patterns in Alzheimer's disease patients

The purpose of this study was to explore the influence of age on regional cerebral blood flow (rCBF) patterns in patients with Alzheimer's disease (AD). Single photon emission computed tomography (SPECT) was performed in 79 patients with AD, including 31 younger and 48 older patients divided according to age at examination (<70 and > or = 70 years), and the SPECT data were analyzed using three-dimensional stereotactic surface projection. Although no significant differences in severity and duration of disease between the two groups were found, there were some differences in rCBF patterns. Patients with younger AD had a more severe decrease of rCBF in the parietotemporal and posterior cingulate cortex, while patients with older AD had a more severe decrease of rCBF in the medial temporal region and medial frontal lobe. This observer-independent analysis of SPECT data provides an objective assessment of cortical rCBF abnormalities in patients with AD and is useful in demonstrating the differences in rCBF patterns between younger and older patients with AD.     

Lack of initiative and interest in Alzheimer's disease: a single photon emission computed tomography study

Apathy is defined as a lack of motivation. The aim of this study was to investigate the relation between two major dimensions of apathy (lack of initiative and lack of interest) and brain perfusion. in patients with Alzheimer's disease (AD). Brain perfusion was measured by single photon emission tomography (SPECT). Thirty-one AD patients were included. Lack of initiative and interest were assessed with the Apathy Inventory. Nineteen AD subjects presented a lack of initiative and interest pathological score whereas 12 AD subjects did not. The lack of initiative and interest score correlated significantly with the right frontal and the right inferior temporal lobes. The AD patients with lack of initiative and interest showed a significantly lower perfusion in the right anterior cingulate than the AD patients without lack of initiative and interest. These results derive from rather small subgroups of patients but have the interest to dismantle the complementary aspects of emotion and motivation in apathy and suggest that the latter one is more related to cingulate area.     

Cortical reorganization for response regulation with unilateral thalamic stroke detected by functional MRI

To understand neural reorganization of response regulation after stroke, a 54-year-old woman with a chronic left thalamic stroke performed a task requiring decisions about the directionality of an arrow during cerebral functional magnetic resonance imaging. Her performance was compared to 13 matched healthy control subjects. Her behavioral responses were slower but as accurate. Bilateral frontal activations were observed in the right medial frontal gyrus (BA 9), left superior frontal gyrus (BA 45), and left frontal rectus gyrus (BA 11). Activation in the right medial frontal gyrus, along with activity in close proximity to the anterior cingulate cortex, was observed, which may reflect reorganization of activity after the loss of function of the anterior cingulate cortex.     

Local gyrification index in patients with major depressive disorder and its association with tryptophan hydroxylase‐2 (TPH2) polymorphism

The tryptophan hydroxylase‐2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD. One hundred and thirteen patients with MDD and eighty‐six healthy controls underwent T1‐weighted structural magnetic resonance imaging and genotyping for TPH2 rs4570625. The local gyrification index of 22 cortical regions in the prefrontal cortex and anterior cingulate cortex was analyzed using the FreeSurfer. The patients with MDD showed significant hypergyria in the right rostral anterior cingulate cortex (P = 0.001), medial orbitofrontal cortex (P = 0.003), and frontal pole (P = 0.001). There was a significant genotype‐by‐diagnosis interaction for the local gyrification index in the right rostral anterior cingulate cortex (P = 0.003). Their study revealed significant hypergyria of the anterior cingulate cortex and prefrontal cortex and an interactive effect between the diagnosis of MDD and the genotype in the anterior cingulate cortex. This might be associated with the dysfunction of neural circuits mediating emotion processing, which could contribute to pathophysiology of MDD. Hum Brain Mapp 38:1299–1310, 2017. © 2016 Wiley Periodicals, Inc.     

Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders

Apathy is a neurocognitive syndrome of reduced goal-directed behaviour and is an important cause of disability in neurodegenerative disorders. Frontal–subcortical dysfunction is thought to be important in apathy, but the contribution of individual brain regions to different aspects of the apathy syndrome is poorly understood. We aimed to test the hypotheses that apathy in two distinct neurodegenerative disorders would be associated with frontal lobe atrophy and that reduced initiative and emotional blunting would be associated with distinct patterns of atrophy in functionally relevant brain areas. Seventeen patients with progressive supranuclear palsy (PSP) and 17 patients with Alzheimer’s disease (AD) underwent structural MRI scanning at 3 T to provide data for voxel based morphometric analysis. Apathy was defined using Robert’s 2009 diagnostic criteria and specific symptoms were assessed with the Apathy Inventory. Patients with and without apathy were matched for important demographic and clinical characteristics. Apathy was associated with atrophy of the ventromedial orbitofrontal cortex and left insula in both AD and PSP. Reduced initiative was specifically associated with atrophy of the anterior cingulate and ventrolateral orbitofrontal cortex whilst emotional blunting was specifically associated with atrophy of the left insula. These findings provide further support for the role of medial frontal regions and insular cortex in apathy and suggest that behavioural and emotional aspects of the apathy syndrome may have distinct neuroanatomical bases.