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Background: The effect of hearing and vision difficulties on the risk of developing dementia and worsening outcomes in people already living with dementia is well established. We evaluated the clinical impact of a hearing and vision rehabilitation and support programme on quality of life in people with mild-to-moderate dementia and concurrent sensory difficulties., Methods: We conducted a parallel-group, multicentre, observer-blind, superiority randomised controlled trial in seven older adult clinics in five European countries (Cyprus, France, Greece, Ireland, and the UK). People with mild-to-moderate dementia with adult-acquired hearing difficulties, vision difficulties, or both were randomly assigned (1:1) along with their care partner to an 18-week home-basedsensory support intervention (SSI) of tailored hearing and vision rehabilitation and support, or to care as usual. Randomisation was blocked (block size of four, six, or eight) and stratified by country, with allocation assigned via a remote web-based system. The SSI included: full hearing assessment, vision assessment, or both; fitting of hearing aids, glasses, or other sensory aids; and home-based support from a sensory support therapist to assist adherence and uptake of sensory aids, foster social networking, and optimise the home sensory environment. Care as usual involved no additional intervention beyond services normally available to people with dementia at the respective sites. The primary outcome was health-related quality of life (Dementia Quality of Life Instrument [DEMQoL]) score at 36 weeks, reported as an adjusted mean difference. Analyses were done according to the intention-to-treat principle. This trial is registered with the ISRCTN Registry, ISRCTN17056211., Findings: Between May 4, 2018, and May 6, 2021, 252 people with mild-to-moderate dementia were randomly assigned, of whom 251 (n=126 in the SSI group and n=125 in the care as usual group) were included in the analysis. The mean age of participants was 79·6 years (SD 5·8), and 132 (53%) were women. After a median follow-up time of 37·7 weeks (IQR 36·2-39·0), the mean DEMQoL score was 92·8 (SD 15·2) in the SSI group and 92·8 (14·0) in the care as usual group (adjusted difference 0·18, 95% CI -2·13 to 2·30, p=0·87). Among 114 adverse events reported for 56 (44%) participants in the SSI group, ten events in nine participants were related or possibly related to the intervention (medical device pain or discomfort n=6, ear pain n=1, scratch to the ear n=1, sore eye n=1, redness n=1; all of grade 1). Serious adverse events were reported for 25 (20%) participants in the SSI group and 16 (13%) in the care as usual group. Six (5%) participants in the SSI group and five (4%) in the care as usual group died. None of the serious adverse events or deaths were related to the study intervention or procedures., Interpretation: This study showed no improvement in quality in life in participants who received the intervention in the longer term. Sensory difficulties are common in people with dementia and interventions aimed at improving sensory-cognitive health should be explored further., Funding: EU Horizon 2020., Competing Interests: Declaration of interests IL declares membership of advisory boards for Biogen, NovoNordisk, and Eisai; honorarium for a lecture and support for attending meetings or travel from Biogen; and membership of the Board of Directors for Lewy Body Ireland (unpaid, charity). CJA and PD were supported by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre under grant BRC-1215-20007. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., (© 2022 The British Psychological Society.)

Objectives: Written text contains verbal immediacy cues-word form or grammatical cues that indicate positive attitude or liking towards an object, action, or person. We asked if adults with moderate-severe traumatic brain injury (TBI) would respond to these cues, given evidence of TBI-related social communication impairments., Methods: Sixty-nine adults with TBI and 74 healthy comparison (HC) peers read pairs of sentences containing different types of immediacy cues (e.g., speaker A said "these Canadians" vs. B said "those Canadians.") and identified which speaker (A or B) had a more positive attitude towards the underlined entity (Task 1); and pairs of sentences comprised of a context sentence (e.g., Fred is asked, "Did you visit Joan and Sue?") and a statement sentence (Fred says, "I visited Sue and Joan.") and were asked to indicate how much Fred liked or disliked the underlined words (Task 2)., Results: HC group scores were significantly higher on Task 1, indicating more sensitivity to cues. On Task 2, TBI and HC group ratings differed across cue types and immediacy types, and the TBI group appeared to have less sensitivity to these cues., Conclusions: Findings suggest that TBI-related impairments may reduce sensitivity to subtle social cues in text.

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 1β [IL-1β] 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-1β, 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-1β, 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.

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., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss. The presence of inflammatory process seems to be playing important role in the progression of the disease. This process is directed by the activated glial cells and it leads to the overproduction of acute phase proteins, complement factors activation and induction of inflammatory enzyme systems. These inflammatory factors can contribute to neuronal dysfunction and cell death. Cytokines belong to the acute phase proteins, which are secreted from glial cells. They can either strengthen the inflammatory reaction or suppress it, adjusting the intensity and duration of the immune response. In the category of cytokines belong several interleukins (ILs) and various factors (TNF-α, TGF-β). Interleukins are involved in complex intercellular interactions among neurons, microglia and astrocytes, as well as intracellular signal transduction events, which are necessary to promote the inflammatory cascade characteristic of AD neuropathology. It has been observed that increased levels of pro- inflammatory cytokines, including tumor necrosis factor (TNF), interleukin 1β (IL-1β), interleukin 6 (IL-6) and interferon γ (IFN-γ), may suspend phagocytosis of amyloid Aβ in brains of patients with AD. Thus, it may interfere with the effective removal of plaque from microglia, promote astrogliosis and neural death. Normally, during immune surveillance, a balance is maintained between pro- and antiinflammatory influences. Yet, during AD, the abnormal accumulation of soluble amyloid oligomers triggers excessive release of pro inflammatory factors, such as cytokines and other acute-phase reactants, out of proportion to the regulatory components, such as IL-4, IL-10, receptor antagonists, interleukin inhibitors and others, ultimately leading to neuronal and synaptic injury and loss and cognitive decline. These changes in the brain parenchyma are often accompanied by changes in levels of these inflammatory proteins in peripheral blood. Even though literature is presenting conflicting studies, efforts are being made for the detection of cytokines in peripheral blood and association of their levels with the progression of AD. Inflammatory pathways, involving the signaling of cytokines, could be potential targets for the prevention of AD and the development of new therapies. The aim of the present work is to review studies indicating a correlation between these inflammatory agents and AD pathogenesis.

Children with moderate to severe traumatic brain injury (TBI) are at risk of developing cognitive-communication disorders that have devastating effects on their school life, family life, and social life. These problems can be difficult for families to describe and may be overlooked by community-based providers who are unfamiliar with TBI sequelae. To support the identification and management of cognitive-communication disorders, we review the common signs and symptoms of these disorders in children with TBI and discuss principles of assessment and intervention., (© 2014 Mac Keith Press.)

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.

In elderly patients, exposure to antipsychotic medication and subsequent withdrawal may lead to the development of persistent extrapyramidal symptoms, possibly including a syndrome suggested to be tardive parkinsonism. We describe a case in which withdrawal of antipsychotics was unexpectedly associated with progressive deterioration, rather than improvement, of extrapyramidal parkinsonian symptoms. Abnormal imaging of presynaptic dopamine transporters (DaTs) using single-photon emission computed tomography (SPECT) with ioflupane I 123 (DaTscan) substantially contributed to the differential diagnosis, suggesting it was likely that the patient had an underlying neurodegenerative disorder that preceded the onset of medicationinduced parkinsonian symptoms. Our report illustrates how novel findings from DaTscan may assist with diagnosing the cause of persistent parkinsonian symptoms after antipsychotic withdrawal and provide insight into the controversial concept of tardive parkinsonism.

Introduction: Apathy has been repeatedly highlighted as a core component of negative symptoms especially with regard to functional outcome of schizophrenia. The purpose of this study was to explore the relationships between apathy, cognitive deficits, and psychosocial functioning in chronic patients with schizophrenia., Methods: Thirty-six chronic patients with schizophrenia and an equal number of matched healthy participants were assessed with the clinician version of Apathy Evaluation Scale (AES-C) along with a comprehensive battery of neuropsychological measures. Functioning was assessed with the Personal and Social Performance scale (PSP) and other symptoms were measured with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia., Results: Apathy was strongly and specifically associated with poorer performance on executive tests in patient group. AES-C was significantly correlated with PSP total score as well as its subscales for social useful activities, personal and social relationships, and self-care. Multiple regression analysis revealed that apathy was the most robust predictor of current psychosocial functioning, accounting for 70% of the variance in functioning, independently of co-existent cognitive deficits. Moreover, executive dysfunction did not predict functional impairment, independently of the effect of apathy., Conclusion: Our findings confirm that apathy has a stronger relationship to functional impairment than cognitive deficits on a cross-sectional basis in schizophrenia. Moreover, they suggest that apathy and executive dysfunction might represent different manifestations of the same syndrome, probably sharing a common neural substrate., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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.

The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years. To date, more than six-hundred genes have been linked to the disorder. However, only a minority of them are supported by a sufficient level of evidence. This review focused on such genes and analyzed shared biological pathways. Genetic markers were selected from a web-based collection (Alzgene). For each SNP in the database, it was possible to perform a meta-analysis. The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias. This produced a list of 15 top-rated genes: APOE, CLU, PICALM, EXOC3L2, BIN1, CR1, SORL1, TNK1, IL8, LDLR, CST3, CHRNB2, SORCS1, TNF, and CCR2. A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles. Moreover, the impact of these genes on complement cascade and cytokine production highlights the role of inflammatory response in AD pathogenesis. Gene-gene and gene-environment interactions are prominent issues in AD genetics, but they are not specifically featured in the Alzgene database.

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., ((c) 2008 John Wiley & Sons, Ltd.)

Psychotic depression is classified as a clinical subtype of major depressive disorder. The combination of an antidepressant with an antipsychotic agent has been demonstrated to be efficacious for the treatment of psychotic depression. However, in elderly patients with psychotic depression, little information is available on the efficacy of such combinations. Therefore, we have evaluated combination treatment for 5 weeks with amisulpride and antidepressants in non-demented elderly patients with psychotic depression. Eleven patients were treated with either citalopram 20-40 mg/day (n=5) or mirtazapine 30-60 mg/day (n=6), and amisulpride 75-100 mg/day for 5 weeks. Clinical status was evaluated at baseline and after 3 and 5 weeks using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale--17 items (HDRS) and the Clinical Global Impression Scale (CGI-S). In 5 of the 11 patients there was remission of depression, while in another 5 patients there was partial remission of depression and in one patient there was no remission. Finally, there was resolution of psychotic symptoms in all the patients involved. One patient developed tremor and rigidity but insisted on continuing with the drug since her psychopathology has improved considerably after the addition of amisulpride to antidepressant treatment. In conclusion, some of the elderly patients with psychotic depression may benefit from the combination of amisulpride and antidepressant pharmacotherapy.

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., (Copyright 2004 John Wiley & Sons, Ltd.)

Context: No rating scales of the neuropsychiatric symptoms of patients with dementia and Alzheimer's disease (AD) have previously been developed or translated., Objectives: To develop a Hellenic translation of the Neuropsychiatric Inventory (NPI), to evaluate it's reliability and validity, and to compare NPI results in Greek patients referred to a neuropsychiatry clinic for either of two reasons: disturbing behaviors evoking embarrassment and disturbing behaviors evoking fear in the caregiver., Methods: The Hellenic translations of the NPI, Brief Psychiatric Rating Scale (BPRS), and Emotional Distress Scale (EDS) were compared in evaluating 29 consecutive referrals of patients with AD., Results: The Hellenic NPI (H-NPI) demonstrated a high degree of internal consistency reliability, and of concurrent validity when compared to the BPRS or the EDS. Patients referred for behaviors evoking embarrassment presented with higher scores on NPI ratings of apathy. However, patients referred for behaviors evoking fear presented with higher scores on NPI ratings of aggression and irritability., Conclusions: These results indicate that the H-NPI is a reliable instrument, able to detect differences in clinically referred groups of AD patients., (Copyright 2004 John Wiley & Sons, Ltd.)