Symptoms In Demented Patients Research Articles

Acute Clinical Impact of COVID-19 Quarantine on Patients with Alzheimer's Disease and Other Dementias: An Observational Study

Background: To control the spread of the new Coronavirus (SARS-CoV-2), several governments planned quarantine. The effects of quarantine on patients with dementia and caregivers are unknown. We aimed to describe the clinical changes in patients with different dementias through a detailed caregivers’ interview. Besides, we evaluated caregivers’ psychological symptoms and the impact on public health services. Methods: Family caregivers of patients with dementia, followed at 87 Italian Dementia Centres, were interviewed 45 days after quarantine declaration. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Main outcomes were patients’ changes in cognitive, behavioural, and motor symptoms. Secondary outcomes were changes in caregivers’ burden, and reorganization of health services. Findings: Between April 14 and April 27, 2020, we screened 4913 patients with dementia. An acute worsening in cognitive functions (+55·1%) and in behavioural symptoms (+51·9%) was reported. Patients with DLB and AD showed the greatest worsening. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioural worsening (odds ratio 1·85 [95% CI 1·42-2·39]; and 1·84 [1·43-2·38], respectively). During the quarantine period, 25·9% of patients showed the onset of new behavioural symptoms. A worsening in motor function was reported by 36·7% of patients. Awareness of the pandemic was negatively associated with increase in cognitive and behavioural symptoms (odds ratio 0·74 [0·65-0·85]; and 0·72 [0·63-0·82], respectively). Finally, an increase of caregiver’s anxiety and depression was reported. Interpretation: Our study shows, for the first time, that quarantine is associated with an acute and dramatic worsening of clinical symptoms in demented patients as well as increase of caregiver’s burden. Primary care physicians and health services need to implement new strategies in order to mitigate the effects of quarantine in patients with dementia. Funding Statement: Italian Society for the Study of Dementias, SINdem. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: The study was initially approved by the Ethics Committee of the Coordinating Centre (University of Torino on April 7, 2020, n.00150/2020) and then by the local ethics boards. Participants gave first oral and then written fully informed consent to the study.

Sharing Transnational Experiences of Psychogeriatric Units Dedicated to the Management of Behavioral and Psychological Symptoms in Demented Patients

The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) is one of the major problems associated with dementia, affecting not only the patient’s outcomes but also the caregiver’s health status and quality of life. Despite the progress in the knowledge of dementia, the management of BPSD continues to be a challenge for physicians and health workers in their everyday clinical practice. Indeed, nonpharmacological approaches are often insufficient to control the manifestation of BPSD if used alone. Nonetheless, studies demonstrated that the pharmacological treatment of BPSD with antipsychotic drugs is burdened by a high risk of adverse events, including extrapyramidal signs, falls, cerebrovascular events, and deaths, and, in this context, models of care attempting to combine nonpharmacological approaches with a careful use of drugs are obviously needed to improve assistance for people with BPSD. Consistent with this approach, the French Government has recently developed a project, the “Plan Alzheimer” 2008 to 2012, in which newly designed intermediate-term care units, Cognitive and Behavioral Units (CBUs), have been created in addition to the traditional referral units, the so-called Acute Psychogeriatric Units (APUs), for the management of patients with BPSD. In a recent issue of Alzheimer disease and associated disorders, Koskas et al reported the results of a pilot study of CBUs, comparing data with those from APUs. The authors found that, in comparison with APUs, patients from CBUs are significantly more cognitively impaired and have more specific BPSD (ie, nighttime and aberrant motor behavior and agitation), while they are less impaired in nutritional and health status. The authors conclude that the 2 programs serve populations with different clinical needs, and, therefore, the 2 settings (ie, CBU and APU) do not act competitively. Another relevant finding is that, according to the physician’s impression, the majority of patients served by either CBUs or APUs showed a marked improvement in their overall condition at discharge. Despite these positive outcomes, however, the findings of the Koskas’ study should be interpreted with caution. The small sample size and the lack of a control group among nonhospitalized patients with dementia limit their conclusions. Moreover, the authors do not address the crucial question of how CBUs and APUs might coordinate their activities in an integrated network of care for patients with dementia and their caregivers. Indeed, a health care delivery system is most efficient if it is able to fulfill its proper aims using all the available resources at a given condition. Therefore, the principle of efficiency requires that the system’s resources be allocated in a synergistic manner to maximize this capacity. In the case of dementia services, this means that each unit of the network not only take care of patients with different clinical needs, but also that the sources of admission and the destinations at discharge from these units are not the same, but the efforts of the different programs remain coordinated. In fact, if sources of patient’s admission and destination at discharge overlap within the 2 settings, the risk of duplicates significantly increases. An Italian experience with the “Plan Alzheimer” of the Lombardia region (8 million inhabitants) addresses this issue of coordination and efficiency. This program was initiated in March of 1995 with the aim to improve the care of patients with dementia, promoting the creation of both Special Care Units (SCU), and Geriatric Evaluation and Rehabilitation Units for Dementia (GERU-D). In addition, in September 2000, 71 Alzheimer’s Evaluation Units (AEUs) were created in the Lombardia region, as a part of a project financed by the

Clinico-pathological correlations in neurodegeneration

During the last years, Acta Neuropathologica has published a number of cluster fascicles focused on special neuropathological subjects, e.g., Alzheimer, Lewy body and prion diseases, brain tumor diagnosis, and animal models of nervous system diseases. Knowledge about clinicopathological correlations in neurodegenerative disorders has been widened, but also obscured by the rapid progress of clinical and basic sciences in detecting essential molecular and genetic backgrounds of these devastating disorders, leading to considerable changes in their traditional classifications and demonstrating multiple, often clinically similar, but biologically different subgroups. The classification of neurodegenerative diseases, previously based on the anatomical systems involved, has progressively been replaced by biologically and genetically defined groups, both promoting and obscuring the clinicians’ views and making exact clinical diagnoses occasionally difficult without molecular pathological background. Neuropathologists as clinical neuroscientists are at the forefront of correlating histological and molecular changes in the brain with neurological features. Accordingly, the idea of reviewing the clinico-pathological correlations of the major neurodegenerative diseases, which should be of interest to both clinicians and basic neuroscientists, was born at the XVIIth International Congress of Neuropathology in Salzburg, Austria, in September 2010. Manuel F. Casanova and colleagues present a critical review of the neuroimaging and morphological correlates of behavioral and psychological symptoms in dementia (BPSD), a subject hitherto rarely discussed in this global form. The review of the literature indicates that BPSD are the expression of regional rather than diffuse brain pathology: psychotic symptoms in demented patients are preferentially associated with the involvement of frontal and/or limbic regions, visual hallucinations with damage to the occipital lobes, apathy with the anterior cingulate gyrus, while white matter lesions appear to be significant for depression. However, BPSD may not be explained by neuropathological findings alone, but are influenced by genetic, neurochemical, environmental, personality, social, and other factors that need further elucidation. Keith A. Josephs and coworkers, based on the pooled data from a number of large clinico-pathological studies, review the neuropathological background of phenotypical variability in frontotemporal dementias (FTD) that currently are classified into three main groups based on the major protein deposits in the brain; frontotemporal lobar degeneration (FTLD)-tau, -TDP, and -FUS. These groups and their specific pathology underly a number of clinical syndromes and the relationships of which are critically discussed. Although strong relationships were identified between FTD with motor neuron disease and FTLD-TDP; semantic dementia and FTLD-TDP, FTLD-tau, and progressive supranuclear palsy (PSP); and the corticobasal syndrome with FTLD-tau, other clinico-pathological relationships are still not clear, although there are some associations between clinical phenotypes and FTLD pathologies. While there remain diagnostic challenges, clinical diagnosis may often predict molecular pathology. Richard Reynolds’ group, based on the broad experience of the UKMS Tissue Bank, present a profound and critical K. A. Jellinger (&) Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria e-mail: kurt.jellinger@univie.ac.at

Clinicopathological correlates of behavioral and psychological symptoms of dementia

Behavioral and psychological symptoms are commonly observed in a majority of demented patients at some time during the course of their illness. Many of these psychiatric manifestations, especially those related to mood, may be early expressions of dementia and/or mild cognitive impairment. The literature suggests that behavioral and psychological symptoms of dementia (BPSD) are an integral part of the disease process. The dissociation, in many cases, between BPSD and the rather linear decline in cognitive functions suggests that independent pathophysiological mechanisms give rise to these symptoms. A review of the neuroimaging and neuropathology literature indicates that BPSD are the expression of regional rather than diffuse brain pathology. Psychotic symptoms in demented patients usually demonstrate preferential involvement of the frontal lobe and/or limbic regions. Visual hallucinations differentiate themselves from other psychotic symptoms by their tendency to involve the occipital lobes. There is a significant association between apathy and structural changes of the anterior cingulate gyrus. White matter hyperintensities occur in a significant number of depressed patients; otherwise, there is lack of association between depression and either specific brain changes or affected regions. Strictly neuropathological explanations are likely to be insufficient to explain BPSD. Environmental changes, neurochemical abnormalities, past psychiatric history (including premorbid personality), social history (e.g., intellectual achievement and life-long learning), family history, and genetic susceptibility are factors, among others, that influence BPSD.

The Pharmacotherapy of Neuropsychiatric Symptoms of Dementia

The neuropsychiatric symptoms of dementia, including aggressiveness, agitation, depression, and apathy are often treated with psychotropic drugs and are a frequent reason for hospitalization, placing an economic burden on the health care system. International guidelines recommend syndrome-specific pharmacotherapy. We studied the question whether drug-prescribing practices are, in fact, syndrome-specific. In a cross-sectional study in 18 homes for the elderly in Berlin, we used syndrome-specific scales to determine the prevalence of apathy, depression, and aggressiveness and the quantity of psychotropic drugs prescribed, in defined daily dosages (DDD), among 304 demented inhabitants. The diagnosis of dementia was ascertained by chart review and confirmed by administration of a mini mental status test. More than 90% of the demented patients had neuropsychiatric symptoms, most commonly apathy (78%). 52% were treated with neuroleptic drugs, 30% with antidepressants and 17% with anti-dementia agents. There was no significant difference between the frequency of neuroleptic treatment given to apathetic and depressed patients and that given to aggressive patients (chi(2) = 7.03; p = 0.32). Although our sample of patients was not representative, these findings suggest that neuropsychiatric symptoms in demented patients are not being treated in syndrome-specific fashion. This is troubling, because neuroleptic medications administered to demented patients can have serious adverse effects, including an elevated mortality. The German guidelines for the treatment of neuropsychiatric disturbances were recently published; the findings presented here suggest that their implementation would be advantageous.

Therapie psychischer Störungen bei Morbus Parkinson

Patients with Parkinson's disease (PD) have a high risk of psychiatric complications, like depressive or psychotic syndromes, dementia and sleep disorders. Although these disorders may even precede the onset of motor symptoms, they are often not recognized and therefore not adequately treated. This article provides a comprehensive overview of the therapeutic options of the most commonly observed psychopathological syndromes in PD. In the case of depressive syndromes medication could be optimized by making use of dopamine agonists that have been proven to have antidepressant properties. In recent studies tricyclic antidepressants showed stronger effects than SSRI. Psychotic symptoms are most often evoked by dopaminergic therapy or are seen in the course of cognitive decline. The therapeutic regimen should be built mainly on L-Dopa medication in the lowest tolerated dose, if required in combinations with COMT-Inhibitors. When antipsychotic medication is indicated, clozapine is the first choice. Quetiapine might also be useful in many patients. Psychotic symptoms in demented patients may respond to cholinesterase-inhibitors, that also delay cognitive decline. Patients with PD require an individually optimized therapeutic regimen not only for motor symptoms, but also for frequently occurring psychiatric syndromes since these strongly influence the patients' and their caregivers' quality of life, are predictors for hospitalization and therefore have great economic importance for health care systems.

Assessing depression outcome in patients with moderate dementia: Sensitivity of the HoNOS65+ scale

To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) “depressive mood” item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F “depressive symptoms” item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, “behavioural disturbance”, “depressive symptoms”, “activities of daily life” and “drug management” items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F “depressive symptoms” item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F “depressive symptoms” item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: A 12-week open-label pilot study

Agitation is one of the most devastating behavioral symptoms in demented patients but there is little evidence about effective and safe pharmacotherapy. We aimed to determine the effectiveness and safety of mirtazapine in treatment of agitated patients with Alzheimer's disease (AD). The consecutive patients with AD who have significant agitation were assigned to a 12-week open-label, prospective study. Patients received mirtazapine 15-30 mg/day. The changes in Cohen-Mansfield Agitation Inventory-Short form (CMAI-SF) scores were primary outcome measurement. The change in Clinical Global Impression-Severity scale (CGI-S) scores and tolerability-safety profile were the secondary efficacy variables. Thirteen of 16 (81.25%) patients completed the study. There was a significant reduction in CMAI-SF and CGI-S between the pre- and post-treatment with mirtzapaine (p < 0.001). The mean baseline score was 26.54 ( +/- 5.4) and mean reduction was 10.6 ( +/- 7.5) in CMAI-SF. There was no significant side effect and cognitive deterioration. The results of this open-label pilot study suggest that mirtazapine may be an effective choice for treatment of agitated patients with AD.

Efficacy of perospirone in the management of aggressive behavior associated with dementia

We assessed the efficacy of the serotonin dopamine antagonist, perospirone (PER) on aggressive and agitated behavior in demented patients. Eighteen outpatients with dementia diagnosed according to the DSM-IV were enrolled in this study, and their behavioral symptoms and cognitive impairments were assessed with the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and Mini-Mental State Examination (MMSE) instruments for a period of 6 weeks. The maximum benefit of PER was achieved at a mean dose of 7.4 mg/day. Post-hoc analysis showed significant improvement in verbal outbursts after 4 weeks and in agitation scores after 4 and 6 weeks. Only 2 patients dropped out of the study, because of adverse effects, and no serious adverse effect was observed. The data suggest that PER is effective in improving aggressive and agitated behavioral symptoms in demented patients and that it is safe to use in elderly patients.

Beneficial effects of perospirone on aggressive behavior associated with dementia

The aim of this study was to assess the efficacy of the serotonin-dopamine antagonist perospirone in treating aggressive and agitated behavior in patients with dementia. Six patients were referred to the outpatient clinic of Ishizaki Hospital and were followed for 6 weeks. Their psychiatric diagnoses were made using the DSM-IV. Their behavioral symptoms and degrees of cognitive impairment were measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and the Mini-Mental Examination State. The changes in BEHAVE-AD scores were investigated. Maximum benefit was achieved at a mean perospirone dose of 9.0 mg/day. No patient experienced severe adverse effects. Post-hoc analysis showed significant improvement in the total BEHAVE-AD and aggressiveness subscale scores within 2 weeks. This study suggests that perospirone is effective in improving aggressive and agitated behavioral symptoms in demented patients and is safe to use in elderly patients.

Depressive symptoms and white matter changes in patients with dementia

The aim of the present study was to investigate if depressive symptoms in demented patients are associated with white matter changes (WMCs) in the brain. WMCs are frequently found in patients with dementia, as well as among elderly nondemented patients with depressive symptoms. However, it is less established whether or not WMCs are related to depressive symptoms in demented patients. 67 (26 men, 41 women) patients with primary degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The patients were young-old (mean 68.1, SD 7.3). All patients underwent a standardized examination procedure and MRI of the brain. The degree of WMCs was visually rated, blindly. Depressive symptoms were rated according to the Gottfries-Bråne-Steen scale (anxiety, fear-panic, depressed mood). No significant relationship was found between WMCs and depressive symptoms in the demented patients. The possible involvement of WMCs in the pathogenesis of depressive symptoms in dementia is unclear. A link between disruptions of frontal-subcortical pathways, due to WMCs, and depressive symptomatology in dementia has been hypothesised from earlier findings, which would imply common elements of pathogenesis for depressive symptomatology and cognitive impairment in dementia. However, the results of the present study do not add further support to this hypothesis.

Hospital admissions for acute onset of behavioral symptoms in demented patients: what do they want to say?

Hospital admissions for acute onset of behavioral symptoms in demented patients: what do they want to say?

Neuropsychiatric inventory. Propiedades psicométricas de su adaptación al español

The purpose of this study was to examine the reliability and validity of the Spanish (Spain) version of the Neuropsychiatric Inventory. The Neuropsychiatric Inventory was administered to the caregivers of 63 subjects from the Dementia Unit, Hospital Santa Caterina, Girona. All patients had detailed neuropsychological assessment, and their non-cognitive symptoms were also examined with the CAMDEX. There was a high level of internal consistency reliability. The Neuropsychiatric Inventory subscores correlated with those of the CAMDEX, indicating an acceptable level of validity. The most frequent symptom was apathy (56%), followed by irritability (38%), depression/dysphoria (35%), aberrant motor behavior (30%), agitation/aggression (29%), anxiety (27%), disinhibition (24%), delusions (19%), hallucinations (14%) and euphoria (3%). This study showed that the Spanish version of the Neuropsychiatric Inventory is a reliable instrument, which can briefly assess non-cognitive symptoms in demented patients. The Neuropsychiatric Inventory is a useful instrument for research and clinical practice in different culture around the world.

How should a group living unit for demented elderly be designed to decrease psychiatric symptoms?

The main objectives were to study relationships between the design of group living (GL) units and psychiatric symptoms in demented patients before, 6 months after, and 1 year after admission to GL units. The study population comprised 105 demented elderly (83 +/- 6 years), 37% with dementia of Alzheimer's type and 58% with vascular dementia. The patients were relocated by the municipal care planning team after clinical examination. An observational scale (the Organic Brain Syndrome scale) was used to assess confusional symptoms and disorientation. The physical environment was assessed by an architect using the Therapeutic Environment Screening Scale, which evaluates general design, space, lighting, noise, communication area, floor plan, and related factors. Less than 15% of the patients had no signs of dyspraxia, hallucinosis, dysphasia, or depression at admission, whereas 66% or more reported lack of vitality, aggressiveness, or restlessness. Fourteen out of 18 units had a corridor-like design (group A), one unit an L-shaped design (group B), and the others a square or H-shaped design (group C). Patients living in the B unit had less disorientation than the others at the 6-month follow-up. After 1 year, the patients in the A units had more dyspraxia, lack of vitality, and disorientation of identity. The communication areas in the units were negatively associated with "disorientation for recent memory" and "lack of vitality," adjusted for type of dementia (r = -0.13 to -0.16). The size of the activity area, indoor public rooms in square meters, was not correlated to confusional reactions and disorientation. In conclusion, a GL unit design that facilitates perception without reducing the communication area is to be preferred.

The Use of Benzodiazepines in the Management of Behavioral Symptoms in Demented Patients

Hard data on the efficacy of benzodiazepines in the treatment of behavioral disturbances in Alzheimer's disease are not available. Short-acting benzodiazepines, such as oxazepam, appear safer than long-acting benzodiazepines and more efficient than placebo in the short-term (4-8 weeks) treatment of behavioral disturbances in geriatric, psychogeriatric, and demented patients. It is unknown whether oxazepam is superior to neuroleptic drugs or other commonly prescribed sedatives in this context. To some extent these findings may apply to patients with Alzheimer's disease as well, but there are several arguments against an uncritical extrapolation of conclusions drawn from other geriatric populations to patients with Alzheimer's disease. When, despite the lack of well-founded knowledge in this field, such a treatment modality is chosen, short-acting benzodiazepines should be preferred over long-acting agents. Drug interactions and pharmacokinetic aspects of the specific agent in the individual patient should always be considered carefully. Future studies on the treatment of behavioral disturbances in Alzheimer's disease need to clarify which specific behavioral symptoms should be treated pharmacologically, which therapeutic agents have the most advantageous risk-benefit ratio in this context, and what is the optimal treatment duration.

Standardised Psychiatric Interview in elderly demented patients.

Twenty patients with dementia were assessed by two raters, using the Standardised Psychiatric Interview of Goldberg et al (1970). Inter-rater reliability was good or fair for many items, but test-retest reliability and validity were less good. A single interview does not appear to provide a full picture of psychiatric (excluding cognitive) symptoms in demented patients.