Neuropathological sequelae of Human Immunodeficiency Virus and apathy: A review of neuropsychological and neuroimaging studies

Apathy remains a common neuropsychiatric disturbance in the Human Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment (ART). The goal of the current review is to recapitulate findings relating apathy to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available literatures demonstrate that the emergence of apathy with other neurocognitive and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An assortment of neuroimaging modalities converge on the severity of apathy symptoms associated with the propensity of the virus to replicate within frontal-striatal brain circuits that facilitate emotional processing. Burgeoning research into functional brain connectivity also supports the effects of microvascular and neuro-inflammatory injury linked to aging with HIV-1 on the presentation of neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV-associated neurocognitive and neuropsychiatric impairment linked to apathy in HIV. Taken together, these lines of research suggest that loss of affective, cognitive and behavioral inertia is commensurate with the neuropathology of HIV-1.     

Apathy in aging: Are lack of interest and lack of initiative dissociable?

Apathy is common in aging and generally defined on the basis of three dimensions: lack of initiative, lack of interest and emotional blunting. Curiously, no study until now has examined the associations and dissociations between these dimensions in elderly people (with or without dementia). These questions were addressed in two studies. In the first study, we explored the distribution of scores and the relationships between the three dimensions of apathy in 56 patients with dementia, focusing mainly on lack of initiative and lack of interest. Apathy was hetero-evaluated with the Apathy Inventory (AI), a scale widely used to assess the apathy dimensions in aging. In the second study, given the AI's limitations, we investigated in more detail the relationship between lack of initiative and interest in 115 elderly people using a new questionnaire specifically designed to assess these two dimensions. Results showed that lack of initiative was closely related to lack of interest (Study 1). Although we used a more specific questionnaire, these facets of apathy did not constitute two separable dimensions, but reflected a common main factor of apathy in aging (Study 2). Thus, the distinction between lack of initiative and lack of interest seems questionable. Only a multifactorial approach that includes the various psychological factors involved in apathy would enable one to gain a better understanding of the different manifestations of apathy and to highlight possible dissociations between them.     

Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson’s disease

BackgroundNotwithstanding the large improvement in motor function in Parkinson’s disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role.ObjectiveWe studied whether apathy in DBS-treated PD patients could be a stimulation effect.MethodsIn 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy.ResultsAverage apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex.ConclusionsThe present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.     

Reduction of white matter integrity correlates with apathy in Parkinson's disease

Background: Apathy is a common non-motor symptom in Parkinson's disease (PD), but little is known about apathy and white matter (WM) change. In this study, we investigated whether fractional anisotropy (FA) of the WM can distinguish apathetic patients from non-apathetic PD patients, and whether the FA value correlates with the severity of apathy in PD.

Methods: Thirty-nine PD patients participated in our study, of which 18 participants were with apathy symptom, and 21 without apathy symptom. Diffusion tensor imaging was performed on all the subjects.

Results: Compared to non-apathetic PD patients, the apathetic group had reduced FA values in the genu and body of corpus callosum, bilateral anterior corona radiata, left superior corona radiata and left cingulum. Furthermore, in these WM regions, the FA values were negatively correlated with the Lille Apathy Rating Scale scores in apathetic subjects.

Conclusion: The WM change is associated with apathy in PD patients. In addition, the FA values of specific regions of WM could be a promising marker to predict the severity of apathy.     

Caregiver perception of apathy in persons with mild cognitive impairment or Alzheimer's disease: a longitudinal study

Objective: Discrepancy between self- and caregiver apathy ratings was examined longitudinally for persons with mild cognitive impairment or Alzheimer's disease. Particular focus was on the distinction between the positive and negative caregiver bias and its predictive value for a clinical diagnosis of apathy.

Method: Apathy rating discrepancy was based on the apathy evaluation scale. Dyads were categorized depending on whether the caregiver reported fewer deficits (positive caregiver bias) or more deficits (negative caregiver bias) than the cognitively impaired person did.

Results: Caregiver ratings and rating discrepancy showed a significant increase from baseline to follow-up. By contrast, self- and clinician ratings showed no change across the two time points. Ratings with a negative caregiver bias remained stable, while those with a positive caregiver bias showed a significant increase in the caregiver ratings but also a significant decrease in the self-ratings. A negative caregiver bias at baseline was significantly related to greater likelihood of having clinical apathy at follow-up, adjusted for an array of control variables.

Conclusion: Positive and negative caregiver bias should be distinguished, as they seem to reflect distinct dyadic processes and are relevant for clinical outcome. Furthermore, negative rating discrepancies can be considered a risk factor for developing apathy.     

Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Subjective cognitive Complaints in early Parkinson's disease patients with normal cognition are associated with affective symptoms

IntroductionSubjective cognitive complaints (SCC) and affective symptoms are highly prevalent in Parkinson's Disease (PD). In early PD, SCC prevalence and its affective correlates, using recommended Movement Disorders Society (MDS) Level II Criteria to define the underlying cognitive impairment, has not been previously explored.MethodsWe recruited 121 participants with early PD from two tertiary hospitals in Singapore. The presence of SCC was defined using a Non-Motor Symptoms Scale Domain-5 Score ≥1. Comprehensive neuropsychological testing was conducted with Mild Cognitive Impairment (PD-MCI) defined using recommended MDS Level II Criteria. Affective symptoms were assessed using the Hospital Anxiety Depression Scale (HADS), Geriatric Depression Scale (GDS) and Apathy Scale (AS). Analysis using multivariable linear regression model was performed.ResultsIn our early PD cohort, SCC prevalence independent of underlying cognitive status was 38.8%. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively (р = 0.241). In cognitively normal PD participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety (β = 0.28, 95% CI = 0.09–0.79, p = 0.014), depression (β = 0.31, 95% CI = 0.10–0.59, p = 0.006) and apathy (β = 0.32, 95% CI = 1.15–5.98, p = 0.004). Such an association was not found in cognitively impaired PD participants.ConclusionSCC is highly prevalent even in early PD. Its implications in early PD differ depending on underlying cognitive status. SCC in cognitively impaired participants underestimates the true prevalence of PD-MCI. In contrast, SCC in cognitively normal participants is suggestive of an underlying affective disorder.