Neurocognitive correlates of alexithymia in asymptomatic individuals with HIV

Alexithymia, an impairment of affective and cognitive emotional processing, is often associated with human immunodeficiency virus (HIV) and may reflect effects of the virus on brain areas that are also important for multiple cognitive functions, such as the prefrontal and anterior cingulate cortices. We hypothesized that there would be a correlation between extent of alexithymia and cognitive performance associated with these brain areas, including attention, executive function, and visuospatial processing. Thirty-four asymptomatic HIV+ participants and 34 matched healthy HIV− volunteers were administered the Toronto Alexithymia Scale, a series of neuropsychological tests, and measures of apathy, depression, and quality of life (QoL). The HIV+ participants had significantly higher levels of alexithymia, depression and apathy than the HIV− group. The extent of alexithymia and two of its processing components (Difficulty Describing Feelings [DDF] and Externally Oriented Thinking), but not depression, correlated with performance on measures of executive and visuospatial abilities, consistent with dysfunction of the frontostriatal circuits and their cortical projections. Apathy was related to alexithymia and two processing components (Difficulty Identifying Feelings and DDF) but to only one cognitive measure. The higher rate of alexithymia, as well as cognitive dysfunction, in HIV may be a consequence of the infection on the frontostriatal system and its cortical connections. Our findings also demonstrated a dissociation of apathy and alexithymia in HIV, pointing to overlapping but distinct neural substrates within frontostriatal circuits. Alexithymia correlated strongly with QoL ratings, underscoring the importance of assessment and treatment of HIV-associated emotional and cognitive processing deficits.     

Apathy is associated with volume of the nucleus accumbens in patients infected with HIV

Apathy refers to a reduction in self-initiated behavior, and it is commonly reported by patients infected with human immunodeficiency virus (HIV). It remains unclear whether apathy among HIV patients reflects a direct effect of the virus on subcortical brain circuits or a secondary neuropsychiatric symptom. In the present study we examined the relationship between ratings of apathy and quantitative analysis of the nucleus accumbens (NA), a subcortical brain structure that regulates initiation of behavioral activation. Twelve HIV-positive individuals without dementia were administered the Marin Apathy Scale and underwent neuroimaging. Voxel-based quantification of the nucleus accumbens was completed using a segmentation protocol. Results of our study revealed that increased ratings of apathy were significantly correlated with lower volume of the nucleus accumbens. By contrast, ratings of depression were unrelated to either apathy or nucleus accumbens volume. These findings provide preliminary evidence that apathy reflects direct involvement of the central nervous system in patients with HIV.     

Neuropsychiatric disturbance is associated with executive dysfunction in HIV-1 infection.

Prominent apathy and/or irritability are frequently observed among individuals infected with the human immunodeficiency virus (HIV). Although these symptoms often occur as part of a mood disorder, compelling evidence suggests that they may occur independently of depression in neurologic disease/disorder. The current study examined the prevalence of both apathy and irritability among a sample of HIV-infected individuals and explored the degree to which these neuropsychiatric (NP) phenomena were associated with performance on neuro-cognitive measures thought to be sensitive to the potential CNS effects of HIV-1. Clinician-administered rating scales assessing apathy and irritability were administered to 65 HIV-seropositive (HIV+) and 21 HIV-seronegative (HIV-) participants who also completed a dual-task reaction time paradigm and the Stroop task. NP disturbance was significantly more prevalent among HIV+ participants compared with HIV- controls and was associated with specific neuro-cognitive deficits suggestive of executive dysfunction. Relative to both HIV- controls and to neuro-psychiatrically intact HIV+ participants, those HIV+ individuals with evidence of prominent apathy and/or irritability showed deficits in dual-task, but not single-task, performance and on the interference condition of the Stroop. Unexpectedly, NP disturbance did not show a robust relationship with HIV disease stage. These results suggest that the presence of prominent apathy and/or irritability among HIV+ individuals may signify greater HIV-associated CNS involvement. In HIV/AIDS, the disruption of frontal-subcortical circuits may be a common mechanism causing both executive dysfunction and NP disturbance.     

Relationship between self-reported apathy and executive dysfunction in nondemented patients with Parkinson disease.

OBJECTIVE: The prevalence of apathy was assessed across select cognitive and psychiatric variables in 32 nondemented patients with Parkinson disease (PD) and 29 demographically matched healthy control participants. BACKGROUND: Apathy is common in PD, although differentiating apathy from motor, cognitive, and/or other neuropsychiatric symptoms can be challenging. Previous studies have reported a positive relationship between apathy and cognitive impairment, particularly executive dysfunction. METHOD: Patients were categorized according to apathy symptom severity. Stringent criteria were used to exclude patients with dementia. RESULTS: Approximately 44% of patients endorsed significant levels of apathy. Those patients performed worse than patients with nonsignificant levels of apathy on select measures of verbal fluency and on a measure of verbal and nonverbal conceptualization. Further, they reported a greater number of symptoms related to depression and behavioral disturbance than did those patients with nonsignificant levels of apathy. Apathy was significantly related to self-report of depression and executive dysfunction. Performance on cognitive tasks assessing verbal fluency, working memory, and verbal abstraction and also on a self-report measure of executive dysfunction was shown to significantly predict increasing levels of apathy. CONCLUSIONS: Our findings suggest that apathy in nondemented patients with PD seems to be strongly associated with executive dysfunction.     

Treating apathy in Alzheimer's disease

Apathy, a syndrome of decreased initiation and motivation, affects over 70% of individuals with Alzheimer's disease (AD) and is the most common neuropsychiatric symptom reported in AD patients. The syndrome of apathy is associated with functional impairment among patients and elevated stress among their caregivers. Apathy is one of the primary neuropsychiatric manifestations of frontal system dysfunction, and AD-related apathy is thought to reflect the interaction between cholinergic deficiency and neuropathological changes in frontal brain regions. This article reviews the assessment and treatment of apathy in AD, with emphasis on the utility of acetylcholinesterase inhibitors for reducing apathy in AD. The potential benefits of other pharmacologic agents and combined pharmacologic-behavioral interventions are also discussed, and recommendations for future research are provided.     

Apathy and cognitive performance in older adults with depression

OBJECTIVES: Recent studies have linked apathy to frontal lobe dysfunction in persons with dementia, but few studies have explored this relationship in older, depressed persons without dementia. We examined the association between apathy and cognitive function in a group of older persons with major depression using standardized neuropsychological tests. We hypothesized that presence of apathy in depression is associated with poorer frontal executive performance. METHODS: We analyzed data from 89 older adults with major depression. We defined apathy using four items from the Hamilton Psychiatric Rating Scale for Depression which reflect the clinical state of apathy, including 'diminished work/interest,' 'psychomotor retardation,' 'anergy' and 'lack of insight.' RESULTS: Apathy most strongly correlated with two verbal executive measures (Stroop C and FAS), a nonverbal executive measure (Wisconsin Card Sorting Test-Other Responses), and a measure of information processing speed (Stroop B). Apathy was not associated with age, sex, education, medical illness burden, Mini-Mental State Examination score and Full Scale IQ score. Stepwise regression analyses of significant cognitive tests showed that apathy alone or apathy plus depression severity, age, or education accounted for a significant amount of the variance. CONCLUSIONS: The results of this study provide support for an apathy syndrome associated with poorer executive function in older adults with major depression.     

Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease.

Apathy is a salient feature of various neuropsychiatric disorders, from depression to Alzheimer's disease. We formally assess its prevalence in idiopathic Parkinson's disease (PD) together with its clinical, neuropsychological, and morphometric correlates. Thirty patients with PD and 25 normal controls were assessed using an extensive neuropsychological battery and Marin's Apathy Scale; parkinsonian patients also underwent MRI scan, followed by linear measurement of various frontotemporal structures. Approximately 45% of the PD sample showed apathy. For comparison analysis, given the unimodal distribution of the apathy scores, the PD sample was divided into three groups on the basis of the apathy tertiles. All three PD groups had worse cognitive and depression scores than controls, whereas they did not differ in terms of demographic, neurological, general cognitive, or affective features. By contrast, a significant positive association was found between apathy scores and performance on tests of executive function. As regards the morphometric data, we failed to find any specific measure of frontotemporal atrophy correlating with the presence or severity of apathy. Thus, apathy seems to be a frequent and important companion of PD, in many cases probably due to a primary motivational impairment, possibly related to a frontosubcortical dysfunction.     

Apathy is associated with white matter abnormalities in anterior,medial brain regions in persons with HIV infection

Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit, which has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current cluster of differentiation 4 (CD4) counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy.     

Actigraphic daytime activity is reduced in patients with cognitive impairment and apathy

ObjectivesApathy is a neuropsychiatric symptom in mild cognitive impairment (MCI) and dementia. This study examines correlations between Apathy Evaluation Scale (AES) ratings and actigraphic measures of daytime activity. The aim of this study is to determine the value of ambulatory actigraphy in the assessment of locomotor deficits as a correlate of apathy in geriatric patients with cognitive impairment.Patients and methodsIn this cross-sectional study a total of 82 participants were recruited, 32 patients with dementia, 21 patients with MCI and 23 elderly controls. Rating scales for apathy (AES) and depression (Beck Depression Inventory, BDI) were completed. To measure daytime activity a wrist-worn actigraph and an established protocol were used. A single measure of mean daytime activity per participant was calculated for further statistical analysis.ResultsIn the two groups of patients with MCI and dementia, apathy is associated with reduced daytime activity, independent of diagnosis (no group by apathy interaction). AES scores correlate significantly with daytime activity. Cognitive impairment reduces daytime activity (effect greater in dementia than in MCI). Daytime activity is negatively correlated with memory deficits.ConclusionAmbulatory actigraphy is a promising method to evaluate self-initiated action as a correlate of apathy in patients with cognitive impairment.     

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.     

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.     

Olfaction and apathy in Alzheimer's disease,mild cognitive impairment,and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.     

Apathy and executive function in Alzheimer's disease.

Apathy is a common behavioral disturbance in patients with Alzheimer's disease (AD). Recent studies have linked the presence of apathy to alterations in frontal lobe functions, but few studies have explored the relationship using standard neuropsychological measures in patients with AD. We administered a comprehensive battery of neuropsychological tests and a behavior rating scale to 80 patients with AD. We explored the relationship of apathy to executive dysfunction. AD patients with apathy performed significantly worse on tests of executive function (WAIS-R Digit Symbol, Trail-Making, Stroop Color Interference Test) than AD patients without apathy. The presence of dysphoria did not modify these results and no significant relationships were found between tests of executive functions and dysphoria. Performance on executive measures as a group were effective in correctly classifying patients as apathetic or nonapathetic with 75% accuracy. Neuropsychological measures not dependent on executive functions were unrelated to apathy. Apathy is associated with executive dysfunction and not with other neuropsychological deficits. Apathy is distinct from dysphoria.     

Neurocognitive effects of HIV, hepatitis C, and substance use history

HIV-associated neurocognitive dysfunction persists in the highly active antiretroviral therapy (HAART) era and may be exacerbated by comorbidities, including substance use and hepatitis C virus (HCV) infection. However, the neurocognitive impact of HIV, HCV, and substance use in the HAART era is still not well understood. In the current study, 115 HIV-infected and 72 HIV-seronegative individuals with significant rates of lifetime substance dependence and HCV infection received comprehensive neuropsychological assessment. We examined the effects of HIV serostatus, HCV infection, and substance use history on neurocognitive functioning. We also examined relationships between HIV disease measures (current and nadir CD4, HIV RNA, duration of infection) and cognitive functioning. Approximately half of HIV-infected participants exhibited neurocognitive impairment. Detectable HIV RNA but not HIV serostatus was significantly associated with cognitive functioning. HCV was among the factors most consistently associated with poorer neurocognitive performance across domains, while substance use was less strongly associated with cognitive performance. The results suggest that neurocognitive impairment continues to occur in HIV-infected individuals in association with poor virologic control and comorbid conditions, particularly HCV coinfection.     

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.     

Behavioural abnormalities contribute to functional decline in Huntington's disease

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.     

Hypokinesia in Huntington's disease co‐occurs with cognitive and global dysfunctioning

Besides chorea, hypokinesia is an important motor disturbance in Huntington's disease (HD) but its clinical, neuropsychiatric, and cognitive functioning correlates are largely unknown. This cross‐sectional study investigates correlates of hypokinesia in HD and its effect on global functioning. Among 150 HD gene carriers, 96 patients were clinically motor manifest. Hypokinesia was assessed using the motor section of the Unified Huntington's Disease Rating Scale and global functioning was measured using the Total Functioning Capacity (TFC) scale. Neuropsychiatric measures included the Apathy Scale and the Composite International Diagnostic Interview for diagnosis of depression. The Mini Mental State Examination (MMSE) and a composite executive cognitive measure were used to assess global and executive cognitive functioning, respectively. Compared with 45 patients with no or mild hypokinesia, 51 patients with moderate to severe hypokinesia showed a significant difference in most clinical and neuropsychiatric variables and had worse cognitive functioning scores. However, using forward logistic regression analysis, poor executive cognitive functioning was the only independent correlate of hypokinesia (OR 7.33; 95% CI: 2.82–19.0; P < 0.001). Hypokinesia score was inversely associated with the TFC score (P < 0.001), also after adjusting for chorea, use of antipsychotics, apathy, and global and executive cognitive functioning. In conclusion, the presence of moderate to severe hypokinesia in HD patients co‐occurs with executive cognitive dysfunction and adversely affects global functioning. © 2010 Movement Disorder Society     

Apathy in Parkinson's disease

OBJECTIVE: To assess apathy in patients with Parkinson's disease and its relation to disability, mood, personality, and cognition. METHODS: Levels of apathy in 45 patients with Parkinson's disease were compared with a group of 17 similarly disabled patients with osteoarthritis. Additional neuropsychiatric data were collected concerning levels of depression, anxiety, and hedonic tone. Personality was assessed with the tridimensional personality questionnaire. Cognitive testing included the mini-mental state examination, the Cambridge examination of cognition in the elderly, and specific tests of executive functioning. RESULTS: Patients with Parkinson's disease had significantly higher levels of apathy than equally disabled osteoarthritic patients. Furthermore, within the Parkinson sample, levels of apathy appear to be unrelated to disease progression. The patients with Parkinson's disease with the highest levels of apathy where not more likely to be depressed or anxious than those with the lowest levels of apathy, though they did show reduced hedonic tone. No differences in personality traits were detected in comparisons between patients with Parkinson's disease and osteoarthritis, or between patients in the Parkinson group with high or low levels of apathy. As a group, the patients with Parkinson's disease tended not to differ significantly from the osteoarthritic group in terms of cognitive skills. However, within the Parkinson's disease sample, the high apathy patients performed significantly below the level of the low apathy patients. This was particularly evident on tests of executive functioning. CONCLUSIONS: Apathy in Parkinson's disease is more likely to be a direct consequence of disease related physiological changes than a psychological reaction or adaptation to disability. Apathy in Parkinson's disease can be distinguished from other psychiatric symptoms and personality features that are associated with the disease, and it is closely associated with cognitive impairment. These findings point to a possible role of cognitive mechanisms in the expression of apathy.     

脑小血管病患者淡漠综合征的临床评定

目的 评价脑小血管病（cerebral small vessel disease,CSVD）患者淡漠综合征的发生情况及临床特征。 方法 回顾性收集2019年1-6月在解放军总医院第七医学中心神经内科诊断为CSVD的住院患者的 临床资料。采用2018年国际淡漠综合征诊断标准进行淡漠诊断。患者淡漠程度、认知功能、抑郁、白 质病变程度及陪护负担分别采用神经精神调查表淡漠分量表（neuropsychiatric inventory-apathy,NPI - apathy）或淡漠评价评定量表临床版（apathy evaluating scale-clinician,AES-C）、老年痴呆量表-认知评 分（Alzheimer’s disease assessment scale-cognition,ADAS-cog）、老年抑郁量表（geriatric depression scale, GDS）、白质损伤Fazekas量表、陪护负担量表（caregiver burden scale,CBS）进行评定,总结评价CSVD 患者淡漠综合征的发生情况及临床相关性。 结果 共纳入67例CSVD患者,平均年龄66.39±5.29岁,男性36例（53.73%）。23例（34.33%）诊断 为淡漠综合征,进一步分析淡漠综合征临床表现,以认知与行为活动减少发生率最高（86.96%）。 淡漠程度与白质高信号严重程度呈正相关（r = 0.301,P = 0.013）,与认知障碍程度呈正相 关（r =0.336,P =0.007）,与抑郁障碍无明显相关性（r =0.186,P =0.458）,与陪护负担呈正相关 （r =0.312,P =0.010）。 结论 淡漠综合征在老年CSVD患者中较常见,主要症状表现为认知障碍与行为活动减少,增加陪 护负担。