Apathy in Mild Parkinson’s Disease: Neuropsychological and Neuroimaging Evidence

Alzahrani, Hamad; Antonini, Angelo; Venneri, Annalena

doi:10.3233/jpd-160809

Cited by 31 publications

(20 citation statements)

References 58 publications

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“…Second, since the pathways of connectivity involved in this symptom are partly dopaminergic circuits, this could be a therapeutic target for the treatment of apathy. This concurs with findings that patients with Parkinson's disease and apathy have reduced connectivity between the limbic striatum and prefrontal cortex suggesting dopamine deficits in the frontostriatal pathways as the cause (Alzahrani, Antonini, & Venneri, 2016;Baggio et al, 2015).…”

Section: Discussionsupporting

confidence: 91%

Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Jones

Marco

Manca

et al. 2019

Cortex

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Background: Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions. Objective: To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD. Methods: Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and nonapathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates. Results: At a pFWE < 0.05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms. Conclusion: Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions.

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Section: Discussionsupporting

confidence: 91%

Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Jones

Marco

Manca

et al. 2019

Cortex

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“…These results could reveal that grey matter atrophy is not yet present because the diagnosis of apathy in our sample has not been established in HSA‐PD and LSA‐PD patients with LARS. There are few studies assessing apathy in PD using T1‐weighted imaging and some of them reported reduced grey matter in temporal, frontal, parietal, insula, and accumbens in apathetic PD patients, although these results were not reported in another study . Although grey matter significant results at corrected level were not found, the regions altered in white matter and FC results are in line with the areas that have been found altered in previous grey matter studies.…”

Section: Discussionsupporting

confidence: 71%

“…Studies using T1‐weighted magnetic resonance imaging (MRI) showed grey matter atrophy in the temporal, frontal, and parietal lobes, insula, and nucleus accumbens . The only study of diffusion weighted imaging did not report any difference in white matter integrity between PD with or without apathy and healthy controls (HC) .…”

Section: Introductionmentioning

confidence: 99%

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study

Lucas‐Jiménez

Ojeda

Peña

et al. 2018

Ann Clin Transl Neurol

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ObjectiveApathy is a common nonmotor symptom in Parkinson's disease (PD) affecting 40% of patients. The aim of the study was to investigate brain changes and correlates of frontal, striatal, and limbic pathways related to subclinical symptoms of apathy in PD patients.MethodsThirty‐two PD patients divided into low‐subclinical symptoms of apathy (LSA) (n = 18) and high‐subclinical symptoms of apathy (HSA) (n = 14) and 25 healthy controls (HC) underwent a T1‐weighted, diffusion‐weighted, and resting‐state functional MRI. Apathy was evaluated with the Lille Apathy Rating Scale. Voxel‐based morphometry, tract‐based spatial statistics, and resting‐state functional connectivity (FC) analyses were performed with a region‐of‐interest approach.Results HSA‐PD showed increased white matter axial and mean diffusivity compared with HC and increased white matter axial diffusivity compared with LSA‐PD. HSA‐PD showed decreased fronto‐striatal and fronto‐limbic FC compared with HC and decreased fronto‐striatal FC compared with LSA‐PD. LSA‐PD showed decreased fronto‐limbic but increased fronto‐striatal FC (hyperconnectivity) compared with HC. No significant differences in grey matter were found. Fronto‐striatal FC and white matter axial and mean diffusivity were associated with symptoms of apathy in HSA‐PD. The fronto‐striatal hyperconnectivity was associated with lower symptoms of apathy in LSA‐PD.InterpretationFindings suggest distinct brain alterations in PD groups with subclinical symptoms of apathy. The increased pattern of activation in LSA‐PD, accompanied with lower apathetic symptomatology, might be the initial manifestation of compensatory mechanisms for dysfunctional limbic pathway. The same pattern of hyperconnectivity has been found in other pathologies and the implication of these abnormalities as a cross‐disease model for initial apathy symptomatology is further discussed.

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“…A wealth of neuroimaging evidence shows that disruption of the components or connectivity of these circuits is strongly linked to apathy across brain disorders, which suggests that common brain systems subserve apathy across different pathologies (Le Heron et al, 2018). In addition, apathy in PD has been shown to be associated with greater levels of atrophy in the dorsal ACC (Alzahrani et al, 2016). The present study showed that apathy severity was negatively correlated with ALFF magnitudes in the dorsal ACC.…”

Section: Discussionsupporting

confidence: 56%

Abnormal Spontaneous Neural Activity in Parkinson’s Disease With “pure” Apathy

Sun

Chen

et al. 2020

Front. Neurosci.

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Background: Apathy is one of the most common non-motor symptoms of Parkinson's disease (PD). However, its pathophysiology remains unclear. Methods: We analyzed resting-state functional magnetic resonance imaging (MRI) data acquired at a 3.0T MRI scanner using the amplitude of low-frequency fluctuation (ALFF) metric in 20 de novo, drug-naïve, non-demented PD patients with apathy (PD-A), 26 PD patients without apathy (PD-NA) without comorbidity of depressive or anxious symptoms, and 23 matched healthy control (HC) subjects. Results: We found that the ALFF decreased significantly in the bilateral nucleus accumbens, dorsal anterior cingulate cortex (ACC), and left dorsolateral prefrontal cortex in patients with PD-A compared to patients with PD-NA and HC subjects. Furthermore, apathy severity was negatively correlated with the ALFF in the bilateral nucleus accumbens and dorsal ACC in the pooled patients with PD. Conclusion: The present study characterized the functional pattern of changes in spontaneous neural activity in patients with PD-A. With the aim to better elucidate the pathophysiological mechanisms responsible for these changes, this study controlled for the potentially confounding effects of dopaminergic medication, depression, anxiety, and global cognitive impairment. The findings of the current study add to the literature by highlighting potential abnormalities in mesocorticolimbic pathways involved in the development of apathy in PD.

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Apathy in Mild Parkinson’s Disease: Neuropsychological and Neuroimaging Evidence

Cited by 31 publications

References 58 publications

Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study

Abnormal Spontaneous Neural Activity in Parkinson’s Disease With “pure” Apathy

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