Comorbid cerebral amyloid angiopathy in dementia and prodromal stages-Prevalence and effects on cognition.

OBJECTIVES: To determine the contribution of cerebral amyloid angiopathy to cognitive impairment in MCI and dementia. METHODS: Patients with subjective memory impairment (SMI), amnestic and non-amnestic mild cognitive impairment ((n)aMCI), Alzheimer's disease (AD), mixed and vascular dementia (MD/VD) from our memory clinic were included in this retrospective analysis. Patients underwent neuropsychological testing and cranial magnetic resonance imaging (MRI). Magnetic resonance imaging data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. ANOVAs were used to investigate the contribution of CAA to cognitive impairment within diagnostic groups and to determine whether differences in cognitive test performance between the diagnostic groups are mediated by total CAA burden. RESULTS: 475 patients (222 male, 253 female) with SMI (n = 47), naMCI (n = 41), aMCI (n = 189), early AD (n = 9), AD (n = 114), MD (n = 71) and VD (n = 4) were included. Mean age was 73.2 (9.9) years. CAA prevalence was 14.9% in SMI, 14.6% in naMCI, 24.3% in aMCI, 22.2% in early onset AD, 18.4% in late onset AD, 46.5% in MD and 25% in VD. Patients with possible and probable CAA were older than patients without CAA. In particular, diagnosis of aMCI, early onset AD, MD and VD showed high CAA prevalence. In AD but not in aMCI, CAA diagnosis significantly influenced test performance in the CERAD word list recall (F (1,78) = 4505; p = 0.037; partial eta-square = 0.055). Differences in cognitive test performance between the diagnostic groups of naMCI, aMCI, AD and MD were mediated by total CAA burden within AAT simply nouns subtest (F (2,39) = 4059; p = 0.025; partial eta-square = 0.172) and in CERAD verbal fluency test (F (3,129) = 3533; p = 0.017; partial eta-square = 0.076). CONCLUSION: This retrospective analysis demonstrates high prevalence rates of CAA in cognitive diagnoses. Our data suggest that comorbid CAA independently impacts cognitive test performance in the course of AD with presumably stage-dependent effects. Especially in patients with AD comorbid CAA additionally impairs memory function. Total CAA small vessel disease burden further modulates psychometric differences in cognitive test performance between diagnostic groups regarding word finding and word fluency capabilities.

[Coincidence of normal pressure hydrocephalus and Alzheimer`s disease: therapeutic implications and open questions]. / Zur Koinzidenz von Normaldruckhydrocephalus und Alzheimer-Demenz: therapeutische Implikationen und offene Fragen.

Normal pressure hydrocephalus (NPH) is prevalent in aging patient populations. Despite its clinical relevance, many patients with NPH may not receive adequate treatment. Because of the frequency of Alzheimer`s disease in these patients, there could be overlapping pathophysiological mechanisms that are as yet incompletely understood. Cerebral comorbidities seem to have negative effects on therapeutic response to ventriculoperitoneal shunting. In order to avoid unnecessary and unsuccessful surgery in highly vulnerable elderly patients, they have to be taken into consideration in the diagnostic process.

[Chronobiological interventions for prevention and treatment of delirium in critically ill patients]. / Chronobiologische Interventionen zur Prävention und Therapie von Delirien bei Intensivpatienten.

Circadian body and behavior rhythms serve to coordinate and maintain the physiological processes in the human body. A disruption of these rhythms frequently occurs in intensive care patients and can be the cause for the development of delirium. This review article discusses the underlying pathophysiological mechanisms and develops a chronobiologically oriented prevention and treatment approach for delirium in the context of intensive care medicine.

Predictors of subjective cognitive deficits in patients with mild cognitive impairment.

BACKGROUND: Detailed examination of cognitive deficits in patients with mild cognitive impairment (MCI) yields substantial diagnostic and prognostic value, specifically with respect to memory. Magnitude and characteristics of subjective cognitive deficits, however, often receive less attention in this population at risk for developing dementia. METHODS: We investigated predictors of subjective cognitive deficits in patients with MCI, using a detailed assessment for such impairments associated with different cognitive domains, as well as demographic and clinical variables including magnetic resonance imaging data. RESULTS: The strongest predictor for subjective memory deficits was depressed mood, whereas subjective performance issues associated with attention or executive functions also corresponded to measurable impairments in the respective cognitive domains. Reduced hippocampal thickness and hemispheric entorhinal cortex thickness asymmetry were associated with objective memory impairment but not with subjective deficits or symptoms of depression. CONCLUSIONS: Whereas low objective memory performance and reduced cortical thickness within medial temporal lobe subregions could be associated with neurodegeneration, greater subjective memory deficits in patients with MCI may indicate psychological burden.

[Consequences of the COVID-19 pandemic for people with schizophrenia, dementia and substance use disorders]. / Folgen der COVID-19-Pandemie für Menschen mit Schizophrenie, Demenz und Abhängigkeitserkrankungen.

The coronavirus disease 2019 (COVID-19) pandemic poses unexpected challenges to social and healthcare systems worldwide. The direct and indirect medical consequences of infection with the novel coronavirus bring healthcare systems to their limits of their capabilities in many places. The neurotropic effects of COVID-19 can result not only in neurological but also in acute and long-term psychological sequelae. In the psychiatric context, the psychological and psychosocial consequences of contact restrictions and lockdowns as well as the effects of daily reports in the media on people with mental disorders must also be taken into consideration. In this article the consequences of the COVID-19 pandemic for people with mental illnesses, especially those with schizophrenia, dementia, and addictive diseases are discussed.

Case of Severe Acute-on-Chronic Lithium Intoxication with 8.6 mmol/l and Prompt Hemodialysis.

Lithium has been the gold standard in the long-term treatment of bipolar disorder for more than 40 years 1. Due to a narrow therapeutic index lithium intoxication still is a common but potentially avoidable clinical problem 2. The possibility of SILENT-syndrome (syndrome of irreversible lithium-effectuated neurotoxicity) illustrates that prevention and optimal treatment of lithium intoxication is vitally important 3.

[Analysis of risk factors, etiology and treatment standard of lithium poisoning]. / Analyse zu Risikofaktoren, Ätiologie und Behandlungsstandard der Lithiumintoxikation.

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning.

Impact of cognitive reserve on clinical and neuropsychological measures in patients with mild cognitive impairment.

OBJECTIVE: Cognitive reserve influences age of onset, speed of progression, and clinical manifestations of Alzheimer's disease. We investigated whether cognitive reserve interacts with clinical and neuropsychological parameters in mild cognitive impairment (MCI). METHODS: In this cross-sectional study, we recruited 273 people (70.6 ± 10.1 years, 54.6% women) suffering from subjective memory complaints (n = 65), MCI (n = 121), or dementia (n = 87). Patients underwent neuropsychological evaluation, laboratory testing, and brain imaging. Additionally, we obtained information on years of education and help-seeking motivation. RESULTS: MCI patients with a university degree were significantly older than those without (71.6 ± 9.6 vs. 66.9 ± 10.3, p = 0.02). University-educated MCI patients demonstrated superior performance in verbal fluency. Intrinsic help-seeking motivation (self-referral) was associated with higher cognitive reserve. Female MCI patients presented with greater intrinsic motivation. CONCLUSION: Cognitive reserve modulates clinical and neuropsychological measures in patients with MCI.

[Folic acid and vitamin B12 determination in the assessment of cognitive disorders : Overview and data analysis from a university outpatient memory clinic]. / Folsäure- und Vitamin-B12-Bestimmung in der Diagnostik kognitiver Störungen : Übersicht und Datenanalyse einer universitären Gedächtnisambulanz.

Vitamin B12 and folic acid deficiencies are particularly frequent conditions in older people. Since these metabolic disorders represent relevant dyscognitive factors, the assessment of vitamin B12 and folic acid levels is essential in the diagnostic approach of cognitive disorders, such as mild cognitive impairment and dementia in an outpatient memory clinic. This article summarizes the relevant diagnostic and therapeutic aspects of vitamin B12 and folic acid deficiencies and their effects on cognition. The literature review is supplemented by a data analysis of a naturalistic cohort of 250 patients from this outpatient memory clinic.

Driving Problems in the Elderly and Cognitively Impaired.

Driving ability in the elderly and cognitively impaired is of growing demographic relevance. Driving represents a complex task for which multiple central resources are needed. In mild cognitive impairment and dementia, we need to closely monitor driving ability, as it gets irrecoverably lost in the course of the disease. In normal aging, people are often able to self-regulate driving behavior with respect to their medical conditions. Some studies demonstrated that older drivers perform well compared with younger drivers. Others suggest a decline of driving ability in the process of normal aging and an increasing involvement of older drivers in car crashes. However, these findings have been questioned because of several possible biases. Therefore, unnecessary driving restrictions need to be avoided. The reliable evaluation of driving ability requires a specialist assessment with detailed neurocognitive evaluation, investigation of medical history and medical history by proxy, as well as on-the-the-road tests. Highlighting current knowledge in this field, we would like to increase our readers' awareness for the complexity of driving-associated challenges in an aging population.

MAPT mutation associated with frontotemporal dementia and parkinsonism (FTDP-17).

We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis.

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management. OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.

Pharmacologic treatment of depression in Alzheimer's disease.

Major depressive disorder and Alzheimer's disease are common among older people, frequently co-occur and severely impact the quality of life. Unfortunately, data on the efficacy of pharmacologic treatment of depressive symptoms in patients with the neurodegenerative disease remain inconclusive. The heterogeneity of treatment study designs, from varying diagnostic specificity to diverse outcome measures, contributes to conflicting evidence across single trials and meta-analyses. In this literature review, we focus on commercially available products for antidepressant treatment in demented individuals and show how insights from randomized controlled trials could still guide and be aligned with common clinical practice.

The effects of mortality salience and conceptual focus in CISM providers: implications for mental health response to mass fatality disasters.

On the basis of terror management theory (TMT) and cognitive-experiential self-theory (CEST), research has demonstrated that when individuals are experientially (rather than rationally)focused, mortality salience (MS) can engender world view defense in the form of increased in-group bias, increased favoritism toward others who uphold cultural values, and greater derogation of those who threaten them. The goal of the present study was to replicate previously observed effects of mortality salience on world view defense in a sample of disaster responders, specifically Criticallncident Stress Management (CISM) providers, and to examine the potential moderating effect of conceptual mode (rational versus experiential) on these effects. Sixty-two participants at the International Critical Incident Stress Foundation's 2011 World Congress were selected for participation in the study. Subsequent manipulation checks revealed that neither,manipulation (mortality salience: MS versus non-MS or conceptual mode: rational versus experiential) was effective. This failure is discussed in terms of the potentially mortality salient nature of conference proceedings that preceded data collection, the depletion of self-control resources required to maintain a rational focus on conference presentations, participants 'need to maintain their focus during future conference presentations, and profession-related practice effects that may have made it easier for some participants to maintain a rational focus.

The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment.

BACKGROUND: The olfactory system is affected very early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD. OBJECTIVE: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors. METHODS: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and a passive odor perception task based on magnetic resonance imaging were performed before and after training. RESULTS: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. Additionally, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation. CONCLUSION: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.