Cognitive Impairment Related to Apathy in Early Huntington’s Disease
To investigate the relationships between cognitive impairment and apathy in patients with early Huntington's disease (HD) and to further explore the influence of depression on the outcome of cognitive changes associated with apathy.
We included 36 early HD patients, among them 20 were apathetic (HDA) and 16 were not (HDnA). The two groups were matched by age, education and severity of disease. Cognitive functions were evaluated by a comprehensive neuropsychological battery that measures memory, attention, executive function, language and visuospatial abilities.
The HDA patients had significantly lower scores on memory, attention and executive function tests when compared with the HDnA patients (p values <0.05). We compared the performance of patients with (50%) and without depression on cognitive tasks and showed that depression per se did not influence performance. Finally, the results demonstrate that interactions between apathy and motor disturbance have a significant effect on cognitive impairment in HD.
The presence of apathy is associated with more severe deficits of attention, executive function and episodic memory in early HD patients. Furthermore, the findings suggest that depression has little or no effect on cognitive deficits. Finally, apathy increased in parallel with both motor and cognitive dysfunction.
Available from: Jeffrey D Long
- "The clinical features of depression are similar to those in the general population , but they are seemingly independent of cognitive decline , despite limited evidence that higher levels of depression can impact cognitive function . Irritability, which is highly correlated with both impulsivity and aggression   similarly correlates with neither disease progression  nor cognitive and motor decline  . Rather there is some indication of increasing irritability in both premanifest   and early disease stages  . "
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Neuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population.
We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD.
DTI data were collected from 39 premanifest and 45 early-HD participants in the TrackHD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO).
For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain.
We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.
Available from: Gabriele Cipriani
- "It was found that apathy is linked to other clinical characteristics such as cognitive deterioration and functional decline, whereas depression was not (Naarding et al., 2009). In early HD patients, the presence of apathy is associated with more severe deficits of attention, executive function and episodic memory (Baudic et al., 2006). It becomes more severe with advancing disease (Naarding et al., 2009). "
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ABSTRACT: Apathy, characterized by lack of motivation and loss of initiative, is a non-cognitive symptom that affects a high proportion, but not all, of patients with all forms of dementia. To explore the phenomenon of apathy in people with dementia, we searched the PubMed and Google Scholar electronic databases for original research and review articles on apathetic behaviors in patients with dementia using the search terms "apathy, behavioral and psychological symptoms, dementia, Alzheimer's disease, Frontotemporal dementia, Dementia associated with Parkinson's disease, Huntington's disease, Vascular dementia". Some nosological aspects, neurobiological basis, and assessment of, as well as, potential benefits of non-pharmacologic and pharmacologic interventions for apathy in dementia are discussed. Greater understanding of apathy will improve the identification, intervention, and treatment of this ubiquitous and pernicious syndrome.
Available from: Anja Vaskinn
- "Apathy is considered a symptom arising from the prefrontal cortex  or from dysfunction in the frontal-subcortical circuits . It's relationship to neurocognitive function has been extensively studied in other brain disorders, such as Alzheimer – (AD) , Parkinson – (PD)  and Huntington disease (HD)  in addition to traumatic brain injury (TBI) . Common to studies of all the above disorders is the finding of a consistent relationship between high levels of apathy and poorer performance on tests representing executive function [19-24]. "
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ABSTRACT: The underlying nature of negative symptoms in psychosis is poorly understood. Investigation of the relationship between the different negative subsymptoms and neurocognition is one approach to understand more of the underlying nature. Apathy, one of the subsymptoms, is also a common symptom in other brain disorders. Its association with neurocognition, in particular executive functioning, is well documented in other brain disorders, but only studied in one former study of chronic patients with schizophrenia. This study investigates the association between apathy and neurocognitive functioning in patients with first episode psychosis (FEP), with the hypothesis that apathy is more associated with tests representing executive function than tests representing other neurocognitive domains.
Seventy-one FEP patients were assessed with an extensive neuropsychological test battery. Level of apathy was assessed with the abridged Apathy Evaluation Scale (AES-C-Apathy).
AES-C-Apathy was only significantly associated with tests from the executive domain [Semantic fluency (r = .37, p < .01), Phonetic fluency (r = .25, p < .05)] and working memory [Letter Number Span (r = .26; p =< .05)]; the first two representing the initiation part of executive function. Confounding variables such as co-occuring depression, positive symptoms or use of antipsychotic medication did not significantly influence the results.
We replicated in FEP patients the relationship between apathy and executive functioning reported in another study for chronic patients with schizophrenia. We also found apathy in FEP to have the same relationship to executive functioning, as assessed with the Verbal fluency tests, as that reported in patients with other brain disorders, pointing to a common underlying nature of this symptom across disorders.
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