Apathy Syndrome Research Articles

Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia.

In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer’s disease (AD).AimsTo identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients.MethodsThis study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered.ResultsPatients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01).ConclusionsApathy is a distinct syndrome among patients with AD and increases with global deterioration.

Neuropsychiatric Disorders following Stroke

Can J Psychiatry. 2010;55(6):339-340. This issue contains 3 In Review articles,1-3 each dealing with different aspects of the mental and emotional disorders associated with stroke. Stroke produces a wide range of emotional disorders, to which I have devoted an entire book4 because of the diversity and complexity of these multiple disorders. The mental disorders associated with stroke are commonly seen in patients without brain injury. These disorders include depression, anxiety disorders, psychotic disorders, and apathy. In addition, however, there are other disorders that occur following stroke that are unique to patients with brain injury. These include disorders such as anosognosia, pathological laughing and crying, catastrophic reactions, and aprosody. I selected depression, apathy, and anosognosia for this In Review series to emphasize the breadth of neuropsychiatric disorders associated with focal brain infarcts. Although depression has been a focus of clinical care and research in psychiatry for many years, apathy, characterized by a lack of drive and motivation, is frequently one of the cardinal features of patients with longstanding schizophrenia and dementia, as well as a common phenomenon of patients with psychomotor retardation and depression. My article with Dr Gianfranco Spalletta1 demonstrates the large amount of research that has been devoted to the study of poststroke depression (PSD). Studies examining the prevalence of depression have included more than 7000 patients worldwide. Increasingly, geriatric psychiatrists are recognizing that a large percentage of late-life depressions are associated with ischemic events in the brain and that small vessel disease producing hyperintensities on a magnetic resonance imaging scan or large vessel disease producing strokes lead to most depressions that have late-life onset among patients without other severe debilitating illness. Psychiatrists are increasingly asked to treat patients with depressive disorders associated with vascular disease, and this In Review includes all of the randomized controlled studies that have been shown to be effective in the treatment of PSD. In addition, evidence is accumulating that depression has a significant influence on the long-term outcome of patients who survive an acute stroke. Recovery in cognitive impairment, physical impairment, and survival are all negatively affected by the existence of PSD. A few studies have shown that these negative consequences of PSD may be counteracted by the administration of antidepressants. However, the most recent clinical trial using antidepressant therapy demonstrated the effectiveness of escitalopram treatment in the prevention of PSD. The In Review article on apathy by Dr Ricardo E Jorge, Dr Sergio E Starkstein, and me2 emphasizes the progress that has been made in identifying and establishing diagnostic criteria for apathy in a wide variety of disorders including stroke. Numerous studies of apathy following stroke have established that this is a common condition occurring in about 1 in 4 or 1 in 5 survivors of acute stroke. The syndrome of apathy includes disturbances in goal-directed behaviour, cognition, and emotion. A general concensus - that apathy includes these 3 areas of amotivation - has led to an effort to include apathy as a disorder in the emerging Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, classification. Although there is no treatment trial that has established the efficacy of a medication that is available worldwide for treatment of apathy, many studies that reported the effectiveness of stimulant medications and (or) dopamine agonists in the treatment of this condition have been included in our article.2 Although apathy does not manifest itself in overt behavioural manifestations, it severely affects both patients and their families. …

Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment

Apathy is an increasingly recognized concomitant of a broad range of central nervous system disorders. Nevertheless, its nosology, pathogenesis and therapy remain shrouded in confusion and controversy. As yet, there is little consensus regarding methods for detecting apathy, or distinguishing it from depression, or for assessing its severity. Many now regard the apathy syndrome as primarily reflecting a lack of motivation that compromises emotional, cognitive, and overt behavioral function. Even though under-recognized and under-diagnosed, apathy hardly appears uncommon: current epidemiologic studies suggest over 10million Americans may be affected. Its reported frequency in various neurologic and psychiatric conditions varies widely, from less than 10 to over 80%, reflecting differences in population characteristics and assessment procedures. Often apathy has been associated with such neurodegenerative disorders as Alzheimer's disease, Parkinson's disease, and fronto-temporal dementia. But it also occurs in those with psychiatric disorders such as schizophrenia and major depression. Clinical, neuropathologic, and neuroimaging observations increasingly suggest that apathy reflects dysfunction of frontal-subcortical circuits, especially those linking the ventromedial prefrontal cortex to related regions in the basal ganglia. Therapeutically, numerous small studies suggest that psychostimulants, dopaminergics, and cholinesterase inhibitors may benefit those manifesting this syndrome. However, no adequately powered, randomized controlled trials have reported success and no medication have ever been approved for this disorder. The accelerating pace of current research nevertheless promises to improve our understanding of apathy and to better address the unmet medical needs of those suffering its consequences.

A Morphometric Analysis of Neuroanatomic Abnormalities in Traumatic Brain Injury

Cognitive and structural brain abnormalities are common following traumatic brain injury (TBI). The authors compared cognition and brain structure in 14 TBI survivors and 28 matched healthy comparison subjects. TBI survivors showed reduced cerebral volume, due mainly to white matter changes, and poorer attention, psychomotor speed, and memory. Severity of white matter abnormality correlated with worse performance on several cognitive measures that distinguished between groups. Using voxel-based morphometry, regions of reduced white matter concentration were found throughout the cerebrum along with more localized gray matter reductions. Findings suggest that diffuse rather than focal aspects of TBI contribute most to cognitive outcome.

Behavioral phenotype in the 9q subtelomeric deletion syndrome: A report about two adult patients

The 9q Subtelomeric Deletion Syndrome (9qSTDS) is clinically characterized by mental retardation, childhood hypotonia, and facial dysmorphisms. Haploinsufficiency of the EHMT1 gene has been demonstrated to be responsible for its core phenotype. In a significant number of patients behavioral abnormalities like aggression, impulsivity, and chaotic behaviors are present as well as epileptic phenomena. Reports about the developmental, behavioral, and neuropsychiatric aspects of 9qSTDS are scarce and mostly limited to young patients only. In this report, the behavioral and neuropsychiatric characteristics of one male and one female middle-aged patient are described in whom the genetic diagnosis, interstitial and telomeric 9q deletion, respectively, was established recently. In both patients a remarkable sleep disturbance, characterized by frequent awakenings and daytime sleepiness, was present as well as a prominent apathy syndrome. The observed motor signs such as rigid flexure of the arms and finger stereotypies persisted over a period of many years and could therefore not be viewed as symptoms of catatonia. It is concluded that the proposed behavioral phenotype of 9qSTDS comprises at least an erratic sleep pattern and an enduring severe apathy.

Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data

Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data

P02-233 - Acute paranoid psychosis due to past chronic mangenese exposure

A male patient aged 49 was referred for evaluation of an acute paranoid psychotic state followed by an apathy syndrome. Since his history, apart from hypertension, did not mention any somatic complaints or psychiatric symptoms, and he had been involved in an adequate professional career as metalworker and welder, MRI- scanning of the brain was performed. There appeared to be bilateral hyperdensity of the globus pallidus, suggestive for chronic manganese (Mn) intoxication. Subsequently, a Mn plasma level of 31 nmol/l (range: 7-20nmol/l) that confirmed the diagnosis.Mn is a trace element that regulates many enzymes and is essential for normal development and body function. Chronic Mn intoxication has an insidious and progressive course and usually starts with complaints of headache, fatigue, sleep disturbances, irritability and emotional instability. Later, several organ systems may be affected leading to increased heart rate and/or blood pressure, elevated total cholesterol levels, and lowered fertility in males. With respect to neurotoxicity, Mn primarily affects the globus pallidus and the striatum of the basal ganglia, and induces damage to the dopaminergic system. This may ultimately lead to dystonic movements and a parkinsonian syndrome that is dominated by generalized bradykinesia and rigidity.As to neuropsychiatry, an array of symptoms may develop up to 30 years after intoxication of which gait and speech abnormalities, cognitive and motor slowing, mood changes and hallucinations are the most common. Psychotic phenomena are rarely reported.In conclusion, subacute psychotic symptoms in the absence of a psychiatric history, may point towards rare occupational diseases.

Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Social disability in schizophrenic, schizoaffective and affective disorders 15 years after first admission

Background Interest in social functioning of people suffering from mental illnesses has been increasing over the last few years. Only few studies have investigated differences in social functioning in affective, schizoaffective and schizophrenic patients in the long-term and in a comparative approach. Method The present study is part of a 15 year follow-up study on patients suffering from severe mental illness. The here reported findings refer to the data of a sample of 177 patients with life-time diagnoses belonging to the schizophrenic, schizoaffective or affective spectrum according to the ICD-10 criteria. Psychopathological, socio-demographic and other illness-related variables were assessed at the index hospitalisation and at the 15 year follow-up evaluation by using the assessment system published by the Association for Methodology and Documentation in Psychiatry (AMDP-system). Information about patients' social disability was assessed by using a modified and further developed version of the WHO disability assessment scale, the (Mannheim) Disability Assessment Schedule (DAS-M scale). Prevalence rates of social disability and differences in the severity of social disability between different groups of mental illnesses were evaluated. And the association between social disability, diagnoses and psychopathology was analysed. Results Compared to affective and schizoaffective patients, schizophrenic patients showed significantly higher levels of social disability in almost all domains. Severe to very severe levels of disability were found in 64% of schizophrenic patients and only in 19% of schizoaffective patients and 5% of affective patients. However, on a descriptive level all three diagnostic groups presented with similar maxima and minima in their profiles of social disability. Multiple regression analyses revealed that the apathy syndrome had the highest impact on the presence of severe social disability with all other psychopathological syndromes, gender, age and diagnosis having no statistically significant influence. Conclusion Findings indicate that patients' disabilities in different diagnostic groups seem to be of a similar quality and nature despite differences in their severity. The impact of psychopathology on disability seems to be more important than the one of diagnosis per se.

Apathy Is Not Depression in Huntington's Disease

Apathy Is Not Depression in Huntington's Disease

Depression in Frontotemporal Dementia

The authors describe mood abnormalities seen in a case series of patients with frontotemporal dementia (FTD). Authors provide a structured review of outpatient and inpatient charts of FTD patients. Three distinct depressive syndromes were identified: The first corresponds to DSM-IV major depression. The second is a syndrome of mood lability with prominent responsiveness to the environment. The third is a syndrome of profound apathy, without other evidence of depression. A variety of mood disorders are seen in FTD, requiring careful attention to differential diagnosis. FTD should be included in the differential diagnosis during the evaluation of older patients with mood abnormalities.

Apathy Due to Cerebrovascular Accidents Successfully Treated With Methylphenidate: A Case Series

Apathy Due to Cerebrovascular Accidents Successfully Treated With Methylphenidate: A Case Series

Cessation of treatment in childhood acute lymphatic leukemia. Long-term observations after meningosis prevention with intrathecal gold colloid radioisotopes and methotrexate

Cytostatic long-term treatment for about 36 months was administered to 18 children with acute lymphatic leukaemia who were in long-term remission (43-98 months). Prophylaxis of meningosis involved intrathecal 198Au colloid and methotrexate. Seven recurrences occurred during the long-term remissions: the bone marrow was involved six times, leukaemic meningosis occurred once. Five out of seven recurrences occurred within one year of cessation of treatment. There were no complications induced by intrathecal radio-gold, such as the apathy syndrome or leukoencephalopathy. Intrathecal methotrexate led to side effects before administration of radio-gold: encephalopathy twice, paraplegia once. Symptoms regressed completely in two children, one child with encephalopathy continues to have symptoms. All three children were given 198Au colloid intrathecally thereafter which was tolerated very well. 198Au colloid represents an alternative for prophylaxis of meningosis with 60Co telecobalt irradiation in leukaemias and non-Hodgkin lymphomas in childhood.

Psychopathology in Verified Huntington's Disease Gene Carriers

Psychopathology in Verified Huntington's Disease Gene Carriers

Symptoms Overlap in Depression, Dementia

Symptoms Overlap in Depression, Dementia

Apathy Syndrome After Traumatic Brain Injury Compared With Deficits in Schizophrenia

The authors compared the severity and clinical profiles of patients with two etiologically different apathy syndromes: apathy after traumatic brain injury (TBI) and deficit schizophrenia (DSS). Patients from both groups were equally apathetic, but those with DSS had more severe anhedonia, blunted affect, and alogia, as measured by the Scale for Assessment of Negative Symptoms. These findings suggest that patients with DSS have a more complex presentation of apathy. Their differences may help to identify anatomical correlates of these apathy syndromes and aid in the design of more effective management strategies for both groups of patients.

Greater Impairment of Ability in the Divided Attention Task Is Seen in Alzheimer’s Disease Patients with Depression than in Those without Depression

Background: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer’s disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. Method: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n = 21) and without (n = 21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin’s group. Results: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. Conclusions: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin’s group, and an impaired capacity for divided attention in AD patients.

Modafinil Therapy for Apathy in an Elderly Patient

To present a case of successful treatment of apathy syndrome with modafinil. A 78-year-old man with dementia and depression was also experiencing apathy that did not respond to antidepressants including escitalopram, a selective serotonin-reuptake inhibitor (SSRI). Escitalopram was discontinued and modafinil, a novel vigilance-promoting agent pharmacologically distinct from stimulants, was used to successfully treat the apathy. The dosage regimen was initiated at 50 mg and titrated to 200 mg/day over 4 weeks. Apathy was assessed using the Apathy Evaluation Scale developed specifically to identify apathy and also to differentiate this from depression. Apathy, a common behavioral problem, is often mistaken for depression; however, apathy differs from depression in symptomatology, clinical presentation, and treatment options. SSRIs, a common treatment for depression, are known to cause or increase apathy. Deficits in the dopamine receptor system are involved in the etiology of apathy; modafinil's increased dopaminergic transmission is thought to help alleviate apathy. Due to its relative lack of drug interactions, modafinil is a good alternative for elderly patients, who often receive multiple medications. Apathy improved significantly after treatment with modafinil in this patient. To the best of our knowledge, as of January 22, 2007, this is the first report of modafinil treatment of apathy syndrome. Modafinil may be useful in treating apathy syndrome. Its role in the treatment of apathy requires further testing in clinical trials.

Lessons From Neuropsychiatry

Lessons From Neuropsychiatry

Can Cognition Survive Heart Surgery?

In this issue of Circulation , Jensen et al1 report that cognitive difficulties were no fewer when off-pump (OPCAB) versus conventional (CCAB) coronary artery bypass grafting was used. This important investigation, a substudy of the Best Bypass Surgery Trial, is a randomized prospective controlled trial that compares OPCAB with CCAB. Although the numbers seem relatively small (ie, 120 elderly patients with a men age of 76 years), the study was carefully powered to show differences in cognitive function at a mean of 103 days of follow-up. Although one could quibble with the details of the neuropsychological tests chosen (mini-mental state examination as a screening test for dementia after randomization but before inclusion, visual verbal learning, concept shifting, Stroop color word interference test, letter-digit coding), the main result is unequivocal. The incidence of cognitive decline was roughly 8%, and no difference between OPCAB and CCAB was found. This disappointing result raises important questions about the mechanisms of neurological injury caused by cardiac surgery and what future strategies might entail. Article p 2790 Early in the development of cardiac surgery, it was psychiatrists who first reported difficulties with thought content and process. Rizzo et al2 reported on 32 patients under the care of Lewis Dexter (cardiologist) and Dwight Harken (cardiac surgeon) who underwent “finger fracture” valvuloplasty surgery for rheumatic mitral valve disease at the Peter Bent Brigham Hospital in Boston. These psychiatrists applied analytical explanations (eg, hysterical fantasies as the heart as a sexual organ, transference to the surgeon, depersonalization, narcissism) to their findings of disordered thinking in many of their patients. Only 50 years later, these explanations sound amusingly antique, but they mark the first organized recognition that the brain could suffer serious damage as a result of cardiac surgery. The neurological complications of cardiac surgery fall into 2 …