Alzheimer's Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers.

BACKGROUND: Neurosyphilis-associated cognitive and behavioral impairment- historically coined as "general paralysis of the insane"- share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer's disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-ß deposition. Consequently, accurate classification and timely differential diagnosis may be challenging. OBJECTIVE: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy. METHODS: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases. RESULTS: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD. CONCLUSION: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.

Categorising a problem: alcohol and dementia.

Alcoholism is a chronic relapsing disorder that can include extended periods of abstinence followed by relapse to heavy drinking. Decades of evidence have clearly shown that long-term, chronic ethanol exposure produces brain damage in humans. The article aims to review the relationship between alcohol use and dementia. Medline and Google Scholar searches were conducted for relevant articles, chapters and books published until 2019. Search terms used included alcohol consumption, alcohol-related dementia, alcohol use disorders, chronic alcoholism, dementia. Publications found through this indexed search were reviewed for further relevant references. Alcohol acts on the central nervous system via both direct and indirect effects, frequently a combination of the two. There is consensus that alcohol contributes to the acquisition of cognitive deficits in late life. However, there are doubts regarding the aetiopathogenesis, nosological status and prevalence of alcohol-related dementia and still, there is much debate over how much alcohol consumption will lead to alcohol-related dementia.

A complication of coronavirus disease 2019: delirium.

COVID-19 is predominantly a respiratory disease. However, some cases exhibit other features including Central Nervous System symptoms. In the older adult, COVID-19 may present with atypical symptoms, including delirium and its complications. The objective of this study is to describe the relationship between the new type of coronavirus infection and delirium. Systematic research (Cochrane Library and PubMed) was carried out (only upper time limit: April 2020). Publications found through this indexed search were reviewed and manually screened to identify relevant studies. Search terms used included "COVID-19, Delirium, Dementia, Intensive Care Unit". We manually added articles identified through other sources (i.e., key journals). Older people are at the greatest risk from COVID-19. If infected, they may present delirium. Moreover, it is not exclusive to older people. Delirium is not inevitable; rather, it is preventable. Delirium prevention programs are even more crucial in the era of COVID-19 and cannot be allowed to wither despite the challenges of integrating delirium prevention with COVID-19 care. An acute change in condition, behaviour, or mental status should prompt a delirium screen. As regards the treatment, it is advisable to use non-pharmacological interventions first where possible. Medication may be needed for patients with agitation where there is intractable distress or high risk to self/others.

Daily functioning and dementia.

Dementia is characterized by a decline in memory, language, problem-solving and in other cognitive domains that affect a person's ability to perform everyday activities and social functioning. It is consistently agreed that cognitive impairment is an important risk factor for developing functional disabilities in patients with dementia. Functional status can be conceptualized as the ability to perform self-care, self- maintenance and physical activity. A person with dementia usually requires help with more complex tasks, such as managing bills and finances, or simply maintaining a household. Good functional performance is fundamental for elderly people to maintain independency and avoid institutionalization. The purpose of this review is to describe functional changes in demented patients, evaluating the variability in subgroups of dementias.

Demência é caracterizada por declínio na memória, linguagem, resolução de problemas e de outros domínios cognitivos que afetam a capacidade de realização de atividades cotidianas e atividades sociais. É consensual que o comprometimento cognitivo é um importante fator de risco para o desenvolvimento de incapacidades funcionais em pacientes com demência. O status funcional pode ser conceituado como a capacidade de realizar autocuidado, automanutenção e atividade física. Uma pessoa com demência geralmente requer ajuda para tarefas mais complexas, como gerenciar contas e finanças, ou simplesmente realizar atividades domésticas. Um bom desempenho funcional é fundamental para que os idosos mantenham a independência e evitem a institucionalização. O objetivo desta revisão é delinear alterações funcionais em pacientes com demência, valorizando os subgrupos variados de demências.

Daily functioning and dementia / Atividades da vida diária e demência

Abstract. Dementia is characterized by a decline in memory, language, problem-solving and in other cognitive domains that affect a person's ability to perform everyday activities and social functioning. It is consistently agreed that cognitive impairment is an important risk factor for developing functional disabilities in patients with dementia. Functional status can be conceptualized as the ability to perform self-care, self- maintenance and physical activity. A person with dementia usually requires help with more complex tasks, such as managing bills and finances, or simply maintaining a household. Good functional performance is fundamental for elderly people to maintain independency and avoid institutionalization. The purpose of this review is to describe functional changes in demented patients, evaluating the variability in subgroups of dementias.

Resumo. Demência é caracterizada por declínio na memória, linguagem, resolução de problemas e de outros domínios cognitivos que afetam a capacidade de realização de atividades cotidianas e atividades sociais. É consensual que o comprometimento cognitivo é um importante fator de risco para o desenvolvimento de incapacidades funcionais em pacientes com demência. O status funcional pode ser conceituado como a capacidade de realizar autocuidado, automanutenção e atividade física. Uma pessoa com demência geralmente requer ajuda para tarefas mais complexas, como gerenciar contas e finanças, ou simplesmente realizar atividades domésticas. Um bom desempenho funcional é fundamental para que os idosos mantenham a independência e evitem a institucionalização. O objetivo desta revisão é delinear alterações funcionais em pacientes com demência, valorizando os subgrupos variados de demências.

Is that schizophrenia or frontotemporal dementia? Supporting clinicians in making the right diagnosis.

Schizophrenia (SCH) and frontotemporal dementia (FTD) are neurobehavioral syndromes characterized by a profound alteration in personal and social conduct. Differential diagnosis between SCH and FTD remains a challenge. In this short narrative review, we summarize evidences regarding similarities and differences between these disorders to support clinicians in making the right diagnosis. Reports of FTD misdiagnosed as schizophrenia or schizophrenia-like psychosis are frequently reported in the literature. The behavioural variant of FTD (bvFTD) along with familial FTD characterized by delusions and hallucinations represent the medical conditions that best illustrate overlaps between psychiatry and neurology. Neuropsychological patterns of core deficits and anatomical and physiological brain alterations primarily concur in differencing such disorders while additional research on genetic alterations and their reflection on clinical phenotypes should be implemented in the near future. In some cases, a correct diagnosis should be made within an interdisciplinary clinical setting by complementary competences and follow-up visits to evaluate pathology evolution.

Uncommon and/or bizarre features of dementia: part IV.

It is well established that the clinical picture of dementias is not clinically homogeneous. For example, non-amnestic presentations of Alzheimer's disease have been referred to as a typical variant. Careful examination of clinical characteristics contributes to understanding the neurobiology of Alzheimer's disease and other dementias and may in turn enhance knowledge of the potential risk factors involved. This study aimed at describing uncommon or bizarre symptoms/syndromes observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published before 2019. Search terms used included dementia, déjà vu, zoophilia, pathological lying, and somatic symptom disorder. Publications found through this indexed search were reviewed for further relevant references. Uncommon/bizarre features of dementia were described as case reports and there were no systematic investigations.

'I am dead': Cotard syndrome and dementia.

Background: Cotard syndrome is a rare condition whose main feature is a nihilistic delusion ranging from the denial of body parts to that of the existence of one's own life or even the entire universe. Objectives: The aim of this article is to review the nosological significance of Cotard syndrome and to explore the disorder among patients with dementia. Methods: Medline and Google Scholar searches were conducted for relevant articles, chapters and books published before 2018. Search terms used included Cotard delusion, Cotard syndrome and dementia, nihilistic delusion. Publications found through this indexed search were reviewed for further relevant references. Results and conclusion: In this narrative review we emphasise the fact that cases of Cotard syndrome involving patients with dementia are reported quite infrequently. Published studies are limited to very short series or isolated cases. Clinicians are obliged to treat the disorder. They should be alert to the potential high risk inherent in this condition. Keypoints Cotard syndrome is a rare condition characterised by nihilistic delusions that may range from negation of existence of parts of the body to delusion of being dead. The prevalence and incidence of this rare syndrome are not known. Since Cotard's syndrome is conceptualised as part of an underlying disorder, several psychiatric and somatic diseases have been associated with the syndrome. The syndrome may occur in patients suffering from dementia.

Uncommon and/or bizarre features of dementia: Part III.

Clinical neurologists have long recognized that dementia can present as atypical or variant syndromes/symptoms. This study aimed at describing uncommon or bizarre symptoms/syndromes observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published before 2018. Search terms used included compulsion, dementia, extracampine hallucination, disordered gambling, humour, and obsession. Publications found through this indexed search were reviewed for further relevant references. The uncommon/bizarre feature of dementia was described as case reports and there were no systematic investigations.

Uncommon and/or bizarre features of dementia. Part II.

In the past decades, clinicians have recognized that dementia may appear as atypical or variant syndromes, as well as the typical form. This study aimed at describing uncommon or bizarre symptoms/syndromes observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published before 2017. Search terms used included delusional jealousy, delusion of pregnancy, dementia, erotomania, folie à deux, and lycanthropy. Publications found through this indexed search were reviewed for further relevant references. The uncommon symptoms/syndromes were described as case reports and there were no systematic investigations.

Eating Behaviors and Dietary Changes in Patients With Dementia.

BACKGROUND: Eating problems and dietary changes have been reported in patients with dementia. OBJECTIVES: The aim of this article is to explore the generalized problems with nutrition, diet, feeding, and eating reported among patients with dementia. METHODS: Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included behavioral and psychological symptoms of dementia, dementia, dietary changes, eating behavior. Publications found through this indexed search were reviewed for further relevant references. RESULTS: Abnormal eating behaviors, eating problems, and dietary changes are present in most people with dementia, especially in the later stages of the condition. CONCLUSION: Individuals with dementia frequently develop serious feeding difficulties and changes in eating and dietary habits. The changes may be secondary to cognitive impairment or apraxia, or the result of insufficient caregiving, or the consequence of metabolic or neurochemical abnormalities occurring as part of the dementing process.

Violent and criminal manifestations in dementia patients.

Although the older adults have been studied as victims of violence, geriatric patients can display violent behavior. The purpose of the present review was to explore the phenomenon of criminal violations and violent acts in people with dementia. The authors used PubMed to search the MEDLINE database and other sources for original research and review articles on criminal and violent manifestation in demented patients combining the terms "criminal manifestation," "violence, aggressive behavior," "homicide," "suicide" and "homicide-suicide" together with "dementia". Possible biomarkers of violence are considered. The present review highlights the risk factors for violence in patients suffering from dementia, and reviews the literature about criminal violations and homicidal/suicidal behavior in this patient group. Geriatr Gerontol Int 2016; 16: 541-549.

Sexual disinhibition and dementia.

To describe inappropriate sexual behaviour (ISB) observed in patients with dementia, we conducted searches using the Cochrane Library, PubMed, and Web of Science to find relevant articles, chapters, and books published from 1950 to 2014. Search terms used included 'hypersexuality', 'inappropriate sexual behaviors', and 'dementia'. Publications found through this indexed search were reviewed for further relevant references. Sexuality is a human's need to express intimacy, but persons with dementia may not know how to appropriately meet their needs for closeness and intimacy due to their decline in cognition. Generally, the interaction among brain, physical, psychological, and environmental factors can create what we call ISB. The most likely change in the sexual behaviour of a person with dementia is indifference. However, ISB in dementia appear to be of two types--intimacy-seeking and disinhibited--that differ in their association with dementia type, dementia severity and, possibly, other concurrent behavioural disorder. Tensions develop from uncertainties regarding which, or when, behaviours are to be considered 'inappropriate' (i.e. improper) or abnormal. While most ISB occur in the moderate to severe stages of Alzheimer's dementia, they may also be seen in early stages of frontotemporal dementia because of the lack of insight and disinhibition. ISB are often better managed by non-pharmacological means, as patients may be less responsive to psychoactive therapies, but non-pharmacological interventions do not always stop the behaviour.

Migraine features in migraineurs with and without anxiety-depression symptoms: a hospital-based study.

BACKGROUND: Migraine, anxiety and depression often coexist. A "neurolimbic" model of migraine has been recently proposed accounting for a dynamic influence of pain, mood and anxiety on the migraine disease. However, very few data exist concerning clinical migraine features in patients reporting anxiety-depression symptoms. OBJECTIVE: Aim of our study was to test differences in clinical migraine features between migraineurs with anxiety-depression symptoms and migraineurs without ones. MATERIALS AND METHODS: We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, triggers, allodynia. Anxiety and depression symptoms were evaluated in each patient by two brief self-reported scales: the generalized anxiety disorder 7-item scale (GAD-7) and the Patient Health Questionnaire 9-item scale (PHQ-9). A cut-off of 5 in both the GAD-7 and the PHQ-9 was considered positive for the presence of anxiety-depressive symptoms. RESULTS: One hundred and one patients (51.5%) had anxiety-depression symptoms (GAD-7 and PHQ-9 ≥ 5). They reported a more headaches/month (p = 0.004), higher number of triggers (p < 0.001), and were more allodynic (p = 0.005). In a binary logistic regression model triggers and allodynia made a unique statistical contribution on reporting anxiety-depression symptoms. CONCLUSION: Our results showed that the presence of anxiety-depression symptoms affects migraine clinical presentation. They are associated with enhanced migraine triggers susceptibility, more ictal allodynic symptoms as well as more headaches/month. An altered sensation in migraineurs with anxiety-depression symptoms could be a result of a lower pain threshold and an increased cortical excitability in a broader context of a neurolimbic dysfunction.

Clinical features associated with ictal osmophobia in migraine.

Olfactory hypersensitivity may occur during migraine attacks and has been found to be very specific for this form of headache. Aim of this study was to investigate if migraineurs with ictal osmophobia have particular clinical features comparing to patients without ictal osmophobia. We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, depression and anxiety symptoms. Migraine triggers both spontaneously and selecting from a specific list. Allodynia during the migraine attack was measured using the Allodynia symptoms check-list 12 (ASC-12). Eighty four (42 %) patients are non-osmophobic vs. 116 patients (58 %) who are osmophobic. After a logistic regression analysis, pain intensity (OR 1.391; p = 0.008) and anxiety (OR 1.099; p = 0.047) were significantly higher while aura (OR 0.421; p = 0.028) is less frequent in osmophobic migraineurs. We found significant differences in clinical features of osmophobic patients in respect to non-osmophobic ones. Ictal osmophobia seems being related to a broader sensorial hypersensitivity that could lead to a more florid clinical presentation.

Sleep disturbances and dementia.

Sleep is a complex behavioural state, the ultimate functions of which remain poorly understood. It becomes more fragmented as we age, with more night-time awakenings and greater tendency for daytime sleep. The magnitude of disordered sleep among individuals affected by dementia has been clearly demonstrated, and disturbed sleep is a major clinical problem in dementia. Comorbid insomnia and other sleep disturbances are common in patients with neurodegenerative disorders, such Alzheimer's disease and other dementing disorders. How and when sleep problems manifest themselves can depend on the type of dementia involved as well as the stage of the dementia. However, differences in sleep pattern presentation show more variation during the initial stages of dementias than they do during the later stages. Effective, pragmatic interventions are largely anecdotal and untested.

Uncommon and/or bizarre features of dementia.

This study aimed at describing uncommon or bizarre symptoms observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published since 1967. Search terms used included uncommon presentation, behavioural and psychological symptoms, dementia, Alzheimer's disease, and fronto-temporal dementia. Publications found through this indexed search were reviewed for further relevant references. The uncommon symptoms are described as case-reports and there are no systematic investigations. Bizarre behaviours arising late in life should be thoroughly investigated as symptoms of dementia.

Apathy and dementia. Nosology, assessment and management.

Apathy, characterized by lack of motivation and loss of initiative, is a non-cognitive symptom that affects a high proportion, but not all, of patients with all forms of dementia. To explore the phenomenon of apathy in people with dementia, we searched the PubMed and Google Scholar electronic databases for original research and review articles on apathetic behaviors in patients with dementia using the search terms "apathy, behavioral and psychological symptoms, dementia, Alzheimer's disease, Frontotemporal dementia, Dementia associated with Parkinson's disease, Huntington's disease, Vascular dementia". Some nosological aspects, neurobiological basis, and assessment of, as well as, potential benefits of non-pharmacologic and pharmacologic interventions for apathy in dementia are discussed. Greater understanding of apathy will improve the identification, intervention, and treatment of this ubiquitous and pernicious syndrome.

Wandering and dementia.

Wandering represents one of many behavioural problems occurring in people with dementia. To consider the phenomenon of wandering behaviour in demented patients, we conducted searches using Medline and Google Scholar to find relevant articles, chapters, and books published since 1975. Search terms used included 'wandering', 'behavioural and psychological symptoms', 'dementia', 'nursing', and 'elopements'. Publications found through this indexed search were reviewed for further relevant references. The term 'wandering' covers different types of behaviour, including aimless movement without a discernible purpose. It is associated with a variety of negatives outcomes. The aetiology of wandering is poorly understood and it remains an unsolved riddle. Wandering is an acutely distressing problem worldwide, both for the patients and caregivers, and it is a major reason for nursing home admission. Evidence on the effectiveness of pharmacological and non-pharmacological interventions is limited. It is possible that management of coexistent psychopathology would help to ameliorate this problematic behavioural disorder.