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.     

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.     

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.     

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.     

Association between apathy/depression and executive function in patients with Alzheimer's disease

ABSTRACTBackground: Apathy and depression may be strongly associated with executive dysfunction in Alzheimer's disease (AD). The Frontal Assessment Battery (FAB) is an instrument for assessing executive function. The dual task paradigm is also useful for assessing divided attention. However, the association between apathy/depression and these tasks is unclear.Methods: Both the FAB and the dual task were used to evaluate AD patients. A two-way analysis of variance was then conducted between the FAB and dual task results and the absence versus the presence of depression or the absence versus the presence of apathy.Results: Of 88 patients with AD, 26 had both apathy and depression, 26 had depression only, 18 had apathy only, and 18 had neither. Total FAB scores and dual task scores differed significantly between the AD patients with depression and those without depression; the scores were also different between those with apathy and those without apathy. Also, a significant interaction between depression and apathy was noted for the total FAB and dual task scores.Conclusions: The deficits in the total FAB and dual task scores were larger in AD patients with both apathy and depression compared with patients with either apathy or depression alone. AD patients with both symptoms may have greater deficits in frontal lobe function relative to AD patients with either apathy or depression alone.     

Predictors of metabolic monitoring among schizophrenia patients with a new episode of second-generation antipsychotic use in the Veterans Health Administration

Background

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.

Methods

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).

Results

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.

Conclusion

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.     

Cognitive impairment related to apathy in early Huntington's disease

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.     

Relationships among apathy, depression, and cognitive impairment in HIV/AIDS

This study was designed to determine whether apathy is associated with neurocognitive symptoms and/or depressive symptoms in HIV/AIDS and also whether apathy is associated with patient expectancies about antiretroviral medication adherence. Seventy-five HIV+ homosexual men and 58 HIV+ women were assessed for depressive disorders and symptoms. Neuropsychological tests measured attention, concentration, learning, memory, executive function, and psychomotor speed. Other measures included Marin's Apathy Evaluation Scale, the Adherence Determinants Questionnaire, CD4 cell count, and HIV RNA viral load. Apathy was consistently related to depression and unrelated to neuropsychological impairment. Patient expectancies regarding medication adherence were unrelated to apathy when the analysis was controlled for depressive symptoms.     

Apathy correlates with cognitive function but not CD4 status in patients with human immunodeficiency virus

Apathy is a prominent neuropsychiatric symptom associated with human immunodeficiency virus (HIV). The increased frequency of apathy in this population may reflect the direct involvement of the virus on the central nervous system (CNS), but the severity of apathy has not been shown to consistently relate to markers of disease activity or other neuropsychiatric complications of the virus. We examined the relationship between ratings of apathy and performance on measures of cognitive function and immune system status in a sample of HIV-infected patients. Apathy was significantly elevated among HIV-infected individuals compared to healthy comparison subjects. Apathy was significantly related to performance on measures of learning efficiency and a measure of cognitive flexibility. Ratings of apathy did not relate to CD4 cell count, but they were associated with disease duration. In addition, ratings of depression were independent of ratings of apathy. These findings suggest that apathy does not co-vary with a proxy measure of active disease status, but apathy does relate to several measures of cognitive dysfunction in patients with HIV. As such, the increased prevalence of apathy among HIV-infected adults may reflect HIV-associated neurologic dysfunction.     

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.     

Frontal-lobe mediated behavioral dysfunction in amyotrophic lateral sclerosis

Background:  Cognitive impairment secondary to frontal lobe atrophy exists in 40–60% of Amyotrophic Lateral Sclerosis (ALS) cases. We aimed to determine the prevalence of frontal-lobe mediated behavioral impairment in (ALS) and to ascertain its relationship to cognitive impairment.
Methods:  Two-hundred and twenty five patients diagnosed with sporadic ALS were evaluated for behavioral dysfunction using the Frontal Systems Behavior Scale (FrSBe), a validated measure used to examine frontal-lobe mediated behaviors, specifically apathy , executive dysfunction and disinhibition ; a total behavior score is also provided. Additionally, a subset of patients also underwent a comprehensive neuropsychological evaluation.
Results:  Changes in the total FrSBe scores were observed in 24.4% of the patients and 39.6% of the patients had impairment in at least one behavioral domain with symptoms of Apathy being the most common (31.1%). Cognitively impaired ALS patients had worse total ( P  = 0.05) and apathy scores ( P  < 0.01); however, behavioral dysfunction was also present in 16% of the cognitively intact patients. Half of the behaviorally intact patients exhibited cognitive impairment. Significant correlations were observed for performance on certain neuropsychological tests (Animal fluency, Block Design, Logical Memory I and Verbal Series Attention Test) and severity of behavioral dysfunction on certain FrSBe sub scores.
Conclusions:  Frontal-lobe mediated behavioral dysfunction appears to be common in ALS. Cognitively impaired ALS patients had greater behavioral dysfunction. Recognition of behavioral and cognitive dysfunction may assist health-care providers and care-givers recognize changes in decision-making capacity and treatment compliance of patients with ALS.     

Depressive symptom quality and neuropsychological performance in dementia

BACKGROUND: It is unknown to what extent depression and cognitive dysfunction are related in subjects with dementia. A limitation of earlier studies is that only general measures of depression have been studied. METHODS: In a sample of 60 subjects with dementia according to DSM-III-R criteria depressive symptoms were divided into factors of mood and motivation disturbance according to a principal components analysis. Correlations were computed between the factor scores and the performance on a number of specific neuropsychological tests. As the symptom content of motivation disturbance suggests subcorticofrontal dysfunction it was hypothesized that this factor is related to impaired executive functions. RESULTS: 77% of the depressive symptoms contributed to the dimension of motivation disturbance and most of these symptoms occurred outside the context of a major depressive episode. Our hypothesis was supported by a significant negative correlation between motivation symptoms and semantic verbal fluency. This relationship seems to have specificity, as both the dimensions of mood symptoms and of general depressive symptoms did not correlate significantly with specific neuropsychological test scores. CONCLUSIONS: The division of depressive symptoms in factors of mood and motivation disturbance contributes to insight into the relationship between depression and cognitive dysfunction in dementia. An advantage of the motivation disturbance factor compared to the regular apathy scales is that it consists of depressive symptoms. Therefore, it becomes evident that apathy or impaired motivation may occur in patients with dementia both in and outside the context of a depressive syndrome.     

Frontal behavioral syndromes and functional status in probable Alzheimer disease.

OBJECTIVE:/Method: The authors used the Frontal Systems Behavior Scale (FrSBe) to determine the frequency of frontal behavioral syndromes in 49 subjects with mild-to-moderate dementia and 23 subjects with severe dementia of Alzheimer disease (AD) and 23 healthy control (HC) participants. RESULTS:/Conclusions: Frontal behavior syndromes occurred with higher frequency in AD. Apathy and executive dysfunction were elevated both in mild-to-moderate and severe AD. Disinhibition was elevated only in severe AD. In AD, apathy was associated with difficulty in basic activities of daily living (ADL), whereas executive dysfunction was related to impairment in instrumental ADLs.     

Prevalence of apathy, dysphoria, and depression in relation to dementia severity in Alzheimer's disease

Apathy is common in Alzheimer's disease (AD) but may be confused with depression due to overlap in symptoms queried in depression assessments. Depression and dysphoria appear to occur less frequently in AD but are better researched. This study examined the relative frequency of these syndromes and their relation to disease characteristics in 131 research participants with probable or possible AD. Apathy was more prevalent than dysphoria or major depression and was more strongly associated with global disease severity, cognitive impairment, and functional deficits. Accurate differential diagnosis of apathy and depression is key to appropriate family education and effective treatment.     

Neuropsychological deficits associated with Alzheimer's disease in the very-old: discrepancies in raw vs. standardized scores.

The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age and 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; Very-Old: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions. Young-Old AD and Very-Old AD groups were comparable in education, gender, dementia severity, and disease duration. Results showed that both AD groups achieved comparable raw scores on all the neuropsychological measures. However, when scores were standardized on the basis of performance of their respective NC groups (i.e., age-corrected z scores), Very-Old AD patients significantly outperformed Young-Old AD patients on tests of executive functions, visuospatial skills, and delayed memory. Furthermore, the relationship between age and memory and executive function deficits in AD was modified by APOE genotype. These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old.     

Executive hypercontrol in obsessive-compulsive disorder: electrophysiological and neuropsychological indices.

OBJECTIVE: Neuropsychological, brain imaging and electrophysiological research have consistently shown a dysfunction of fronto-striato-thalamic pathways in subjects with obsessive-compulsive disorder (OCD). The functional meaning of the observed dysfunction in the pathogenesis of OCD is still debated. In the present study the hypothesis that it might be related to a hyperactive executive control is explored by means of neuropsychological and electrophysiological measures. METHODS: Multilead quantitative EEG (QEEG) characteristics and neuropsychological performance on tests exploring executive functions, attention, short-term memory and the ability to learn supraspan recurring sequences were investigated in 32 drug-free patients with DSM-IV OCD. Multilead QEEG characteristics were also investigated in 32 healthy controls, matched with patients for age, gender and handedness. RESULTS: A decrease of the slow alpha-band power in OCD as compared to healthy subjects was observed. A significant negative correlation between the slow alpha-band power and the time to complete a neuropsychological test exploring executive functions was found: the more reduced the slow alpha-band power, the slower the performance on this test. CONCLUSIONS: The topographic distribution of the observed QEEG abnormalities, as well as their correlations with neuropsychological indices, suggest an increased activation of frontal networks in OC patients. SIGNIFICANCE: Study findings support the presence of a hyperactivity of attention/executive control mechanisms in obsessive-compulsive patients.     

Apathy in drug-naïve patients with incident Parkinson’s disease: the Norwegian ParkWest study

Apathy is a common behavioural problem in Parkinson’s disease (PD), with important clinical consequences for patients and their families. However, little is known about apathy in early PD. We examined the frequency and clinical characteristics of apathy in 175 nondemented, drug-naïve patients with newly diagnosed PD and 165 control subjects matched for age, sex and education level in Western and Southern Norway. All participants underwent a comprehensive neurological, psychiatric and neuropsychological evaluation. Apathy was diagnosed based on Neuropsychiatric Inventory assessment and recently proposed consensus criteria. Apathy was found in 22.9% of the PD patients, of whom 37.5% had significant depressive symptoms, whereas none of the control subjects were apathetic. Apathy was significantly associated with male gender, higher depression scores and more severe motor symptoms, but was not associated with greater cognitive impairment. When excluding patients with significant depressive symptoms, apathy remained significantly associated with motor severity. Approximately 50% of the caregivers of patients with apathy reported the apathetic behaviour to be at least moderately distressing. The association between apathy and motor severity in our PD cohort suggests a common underlying pathophysiological mechanism. Future studies should explore the longitudinal effect of dopamine replacement therapy on apathetic behaviour in early PD. The relationship between apathy and male gender needs further study to be fully evaluated.     

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.     

Executive dysfunction and loss of capacity to consent to medical treatment in patients with Alzheimer's disease

Loss of medical decision making capacity (competency) is an inevitable consequence of Alzheimer's disease (AD) and is an important subject for neuropsychological investigation. Consent capacity involves a complex set of comprehension, encoding, information processing, decision making, and communication abilities, which ultimately must have an explicit neurological basis. This article examines the role of executive dysfunction in loss of consent capacity in patients with AD. The authors first describe a cognitive neuropsychological model for understanding loss of consent capacity in AD. The article also reviews neuropsychological studies that have used a psychometric instrument to test consent capacity under different legal standards (Capacity to Consent to Treatment Instrument). These studies indicate that when multiple cognitive functions are associated with declining competency of AD patients on the Capacity to Consent to Treatment Instrument legal standards, measures of simple executive function are the predominant predictors. These empirical findings are discussed and related to the conceptual model. The findings support the growing body of literature linking frontal neural systems and executive cognitive functions to competency and to higher order functional capacities.     

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.