A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders.

OBJECTIVE: Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed. DESIGN: A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised. RESULTS: In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects. CONCLUSIONS: Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.

Preserved visuospatial abilities in absence of the right hemisphere: A case of cerebral hemiatrophy with minimal cognitive impairment.

Cerebral hemiatrophy is a rare neurological condition, usually resulting in severe and diffuse cognitive impairment. In this paper we present a 69-year old woman with notable congenital hemiatrophy with strikingly preserved cognitive functions. Cognitive assessment indicated that although her executive functions were found impaired, the remaining cognitive domains were relatively unaffected. We argue that this unexpected cognitive profile may be explained by anomalous hemispheric lateralization, driven by neuroplasticity along the developmental course.

Unmet Needs in Pharmacological Treatment of Apathy in Alzheimer's Disease: A Systematic Review.

Background: Apathy is one of the most prevalent neuropsychiatric symptoms encountered in Alzheimer's disease (AD) and may be an early sign in the development of dementia persisting over the disease course. It has been associated with poor disease outcome, impaired daily functioning, and significant caregiver distress. Early diagnosis and timely treatment of apathy in AD are of great importance. However, approved agents for apathy are still missing. Methods: Within this context, we conducted an extensive electronic search in the databases included in the National Library of Medicine, PsychInfo, and Google Scholar for studies that have investigated the effect of pharmacological treatments in apathy in AD. There were no limitations regarding study design and all care settings were considered for inclusion. Structured measures for level of evidence and study quality were employed to evaluate the results. Results: A total of 1,607 records were identified; 1,483 records remained after the removal of duplicates and were screened; 166 full-text articles were selected and assessed for eligibility and a remaining 90 unique studies and relevant reviews were included in the qualitative synthesis. Acetylcholinesterase inhibitors, gingko biloba, and methylphenidate were found to be successful in reducing apathy in patients with AD. Methodological heterogeneity in the studies and the small amount of studies where apathy was the primary outcome are limiting factors to assess for group effects. Conclusions: Pharmacological treatment of apathy in AD is an underexplored field. Standardized and systematic efforts are needed to establish a possible treatment benefit. Elucidating the pathophysiology of apathy and its components or subtypes will inform disease models and mechanistic drug studies that can quantify a benefit from specific agents for specific AD groups.

Acetyl Cholinesterase Inhibitors and Cell-Derived Peripheral Inflammatory Cytokines in Early Stages of Alzheimer's Disease.

BACKGROUND: Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response. METHODS: This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukins 1ß [IL-1ß] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls. A subset of those drug-naïve AD patients, who were prescribed the AChEI donepezil, was followed-up for 6 months to investigate if donepezil suppresses proinflammatory cell-derived cytokine secretion. RESULTS: Patients with AD showed higher levels of PBMC-derived proinflammatory cytokines (IFN-γ, TNF-α, IL-1ß, and IL-6) in comparison with healthy controls. On reexamination, previously drug-naïve AD patients who received donepezil treatment for 6 months displayed a decrease in cell-derived IFN-γ, TNF-α, IL-1ß, and IL-6. CONCLUSIONS: Proinflammatory PBMC-derived cytokines were increased in patients with AD in comparison with healthy controls and donepezil-reduced proinflammatory cytokines when examining drug-naïve AD patients before and after AChEI treatment.

Apathy associated with neurocognitive disorders: Recent progress and future directions.

INTRODUCTION: Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. METHODS: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. RESULTS: Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. DISCUSSION: Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention.

A Review of Pharmacological Treatments for Depression in Alzheimer's Disease.

Depression in Alzheimer's disease (dAD) is one of the most common behavioral and psychological symptoms of dementia, with devastating consequences not only for the affected individuals, but for caregivers as well. So far, pharmacological treatment of dAD has been based on the "monoamine hypothesis". However, the reported moderate effects of approved antidepressants, as well as an increasing body of research evidence, suggest a more complex pathophysiologic mechanism. In the present paper, a systematic review of different treatments for dAD is presented that can inform the study of alternative neuropathological and neurobiological aspects of the disease aimed at the development of more effective treatment targets.

Cardiac rhythm management devices and electroconvulsive therapy: a critical review apropos of a depressed patient with a pacemaker.

Electroconvulsive therapy (ECT) is an effective treatment and, with the proper risk-minimizing strategies, is relatively safe even in depressed patients with cardiovascular diseases. Specifically, patients with cardiac rhythm management devices (CRMDs) require particular attention because no controlled trials exist to support current empirical recommendations. We present a depressed patient with a pacemaker successfully treated with ECT, and we critically review the relevant literature. Pooled results from 63 patients and 821 ECT sessions showed that 90% of ECT sessions have been performed on depressed patients with their pacemakers in sensing mode and rate adaptation, where available, activated as well. Only 4% of sessions were performed with those functions disabled, whereas no data was available for 6% of ECT sessions. Pooled results from case series and reports highlight a discrepancy between current clinical practice and many guidelines. Electroconvulsive therapy is probably safe in depressed patients with asynchronous fixed-rate pacemakers, although there is a risk of ventricular tachycardia and fibrillation. A larger body of case series and reports suggests that there might be no need to convert synchronous demand pacemakers to asynchronous fixed-rate pacing. Regarding patients with implantable cardioverter defibrillators, antitachycardia treatment was deactivated during most ECT sessions. In depressed patients with CRMDs anticholinergics might be best avoided. In all cases, proper ECT procedures, namely, patient and pacemaker electrical isolation, strict grounding and adequate muscle relaxation along with interrogation and monitoring of CRMDs before and after each session should ensure uncomplicated electroconvulsive treatments.

Amisulpride for the treatment of very-late-onset schizophrenia-like psychosis.

BACKGROUND: Although schizophrenia affects all age groups, late or very-late-onset schizophrenia-like psychosis has not been well studied and various treatment issues remain unresolved. The objective of the present study was to evaluate the efficacy and safety of amisulpride monotherapy in a diagnostically homogeneous group of elderly patients without cognitive impairment suffering from very-late-onset schizophrenia. METHODS: Twenty-six patients of mean age 76.2 +/- 5.8 years, fulfilling both the recent consensus criteria for very late-onset schizophrenia-like psychosis and the DSM-IV-TR criteria for schizophrenia, were assessed by the Brief Psychiatric Rating Scale, the Clinical Global Impression Scale and the Positive and Negative Syndrome Scale at baseline and five weeks following amisulpride (50-200 mg/day) administration; also, the presence of abnormal movements was evaluated with the Simpson-Angus Scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale. RESULTS: A highly significant (p < 0.001) improvement on all measures of psychotic symptomatology was observed in all patients. Amisulpride was very well tolerated by the patients and no clinically significant adverse effects were observed. Scores on all abnormal movement scales did not differ significantly prior to and after amisulpride treatment. CONCLUSION: Preliminary results indicate that amisulpride appears to be an efficacious and safe atypical antipsychotic for the treatment of very-late-onset schizophrenia-like psychosis.

A randomized, controlled, clinical trial of activity therapy for apathy in patients with dementia residing in long-term care.

BACKGROUND: Apathy is a common symptom in patients with dementia and has adverse consequences for patients and caregivers. Most treatments for apathy, particularly non-pharmacologic interventions, have not been evaluated in controlled trials. OBJECTIVES: This study evaluated the efficacy of a kit-based activity intervention, compared to a time and attention control (one-on-one meetings with an activity therapist) in reducing apathy and improving quality of life in 37 patients with dementia. METHODS: The design was a randomized, controlled, partially masked clinical trial. All outcome measures were administered at baseline and follow-up. The primary outcome measure was the apathy score of the Neuropsychiatric Inventory (NPI). Other outcome measures were the NPI total score, the Alzheimer Disease Related Quality of Life scale(ADQRL), and the Copper Ridge Activity Index (CRAI). RESULTS: There was a significant reduction in NPI apathy scores in both treatment groups. The only significant difference between the two treatment groups was a modest advantage for the control intervention on the CRAI cueing subscale (p = 0.027), but not on the other CRAI subscales. There was also a greater within group improvement in quality of life ratings in the control intervention (p=0.03). CONCLUSIONS: Despite the substantial improvement in apathy scores during the course of the study, there was no clear advantage to the reminiscence-based intervention over the time and attention, one-on-one control intervention. More research is needed to develop specific behavioral interventions for apathy in patients with dementia.