Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.

Adult attention-deficit/hyperactivity disorder symptoms, cognitive dysfunction and quality of life in high-dose use of benzodiazepine and Z-drug.

High-dose use of benzodiazepines (BZDs) and Z-drugs was found to be associated with adult attention deficit/hyperactivity disorder (ADHD) and multidomain cognitive deficits, but the interplay between these factors and its effect on quality of life (QoL) is unclear. We explored (a) whether cognitive dysfunction differs in high-dose BZD/Z-drug users with and without adult ADHD and (b) the impact of cognitive deficits and adult ADHD on QoL in this substance-use disorder (SUD). From January 2015 to December 2019, we recruited 207 high-dose BZD/Z-drug users seeking treatment. We assessed the presence of adult ADHD with a screening tool, which was validated in SUD patients, and collected demographic, clinical and QoL data from the 76 included patients. A neuropsychological battery explored five cognitive domains. We found that: (a) screening for adult ADHD was frequently positive; (b) Short Form-36 (SF-36), a self-administered QoL questionnaire, was worse than the general population and worse in patients positive (ADHD+) vs. those negative (ADHD-) to ADHD screening tool; (c) executive function was significantly worse in ADHD+ than ADHD- patients; (d) some SF-36 dimensions were negatively influenced by executive dysfunction; (e) multivariate analysis showed an interplay between adult ADHD and cognitive dysfunction in worsening QoL. We documented a complex interplay between adult ADHD, cognitive dysfunction and QoL in high-dose BZD/Z-drug users. Assessing adult ADHD, neuropsychological measures and QoL may offer a full scenario of these patients, who are frequently impaired in everyday activities. Future research should explore whether pharmacological treatment might improve cognitive dysfunction and QoL in this SUD.

Olfaction in patients with Parkinson's disease: a new threshold test analysis through turning points trajectories.

Olfactory deficit is a widely documented non-motor symptom in Parkinson's disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition. Sixty healthy subjects served as controls. Patients and controls underwent a comprehensive olfactory evaluation with the Sniffin' Sticks extended test assessing threshold, discrimination and identification and a full neuropsychological evaluation. Besides, threshold test data were analyzed examining all the turning points trajectories. PD patients showed a different olfactory threshold test pattern, i.e., faster olfactory adaptation, than controls with no effect of age. Normosmic PD patients showed different olfactory threshold test pattern, i.e., better threshold score, than normosmic controls. Visuospatial dysfunction was the only factor that significantly influenced this pattern. Olfactory threshold trajectories suggested a possible adaptation phenomenon in PD patients. Our data offered some new insights on normosmic PD patients, which appear to be a subset with a specific psychophysical profile. The analysis of the turning points trajectories, through an olfactory threshold test, could offer additional information on olfactory function in PD patients. Future larger studies should confirm these preliminary findings.

The Effectiveness of Cognitive Behavioral Therapy Techniques for the Treatment of Substance Use Disorders: A Narrative Review of Evidence.

ABSTRACT: Substance use disorders (SUDs) are characterized by a recurrent and maladaptive use of drugs and/or alcohol. Cognitive behavioral therapies (CBTs) comprise different types of interventions: traditional CBT and the more recent "third wave" behavior therapies, such as acceptance and commitment therapy (ACT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and schema therapy (ST). We searched English-language articles published between 2014 and present. This review includes randomized controlled trials (RCTs), quasi-RCTs, pilot studies, and reviews of CBTs for SUDs available on PubMed. Results seem to indicate that CBT and MBCT are effective interventions for SUDs; however, the studies showed a high degree of heterogeneity, so no exhaustive conclusions could be outlined at this time. ACT and DBT in SUD management are limited to few studies and results are therefore inconclusive.

Olfaction and taste in Parkinson's disease: the association with mild cognitive impairment and the single cognitive domain dysfunction.

Mild cognitive impairment (MCI) and chemosensory dysfunction are non-motor symptoms of Parkinson's disease (PD), but their association is unclear. We explored if MCI and the involvement of single cognitive domains influence olfaction and taste in PD. The role of demographic, clinical and neuropsychiatric variables was tested. We recruited 50 PD patients without dementia, no other reasons for cognitive impairment, no condition that could influence evaluation of cognition, olfaction and taste. They underwent a full neuropsychological and chemosensory (i.e., olfaction and taste) test with the Sniffin' Sticks Extended test (SSET), Whole Mouth test (WMT) and Taste Strips test (TST). Fifty age- and sex-matched healthy subjects served as controls. Olfactory function and sweet identification were worse in PD than controls. MCI negatively influenced odor identification. Factors associated with poor olfactory function were age, overall cognition, apathy, and visuospatial dysfunction. Sour identification was affected by MCI and executive dysfunction, and salty identification by executive dysfunction. MCI, age and executive dysfunction worsened TST score. Awareness of olfactory dysfunction was impaired in PD with MCI. Education positively influenced SSET and TST scores. Our data confirmed that olfaction is abnormal in PD, while taste was only slightly impaired. Olfaction was worse in PD patients with visuospatial dysfunction, while sour and salty identification was worse in those with MCI and executive dysfunction, suggesting different underlying anatomical abnormalities. Future studies should incorporate neuroimaging and cerebrospinal fluid data to confirm this hypothesis. SSET odor identification and TST sour identification could be explored as quick screening tests for PD-MCI.

Neuropsychological testing.

Neuropsychological testing is a key diagnostic tool for assessing people with dementia and mild cognitive impairment, but can also help in other neurological conditions such as Parkinson's disease, stroke, multiple sclerosis, traumatic brain injury and epilepsy. While cognitive screening tests offer gross information, detailed neuropsychological evaluation can provide data on different cognitive domains (visuospatial function, memory, attention, executive function, language and praxis) as well as neuropsychiatric and behavioural features. We should regard neuropsychological testing as an extension of the neurological examination applied to higher order cortical function, since each cognitive domain has an anatomical substrate. Ideally, neurologists should discuss the indications and results of neuropsychological assessment with a clinical neuropsychologist. This paper summarises the rationale, indications, main features, most common tests and pitfalls in neuropsychological evaluation.

Multifocal cognitive dysfunction in high-dose benzodiazepine users: a cross-sectional study.

Benzodiazepines (BZDs) are the most widely prescribed drug class in developed countries, but they have high potential for tolerance, dependence and abuse. Cognitive deficits in long-term BZD users have long been known, but previous results might have been biased by patients' old age, coexisting neurological or psychiatric conditions or concurrent alcohol or psychotropic drug dependence. The study was aimed to explore the neuropsychological effect of high-dose BZD dependence, which represents an emerging addiction phenomenon. We recruited a group of high-dose BZD users with neither neurological or psychiatric comorbidity except anxiety or depression nor concurrent alcohol or psychotropic drug dependence. They underwent a battery of cognitive tests to explore verbal, visuospatial memory, working memory, attention, and executive functions. All the neuropsychological measures were significantly worse in patients than controls, and some of them were influenced by the BZD cumulative dose. The severity of depression and anxiety had a minimal influence on cognitive tests. Patients with high-dose BZD intake show profound changes in cognitive function. The impact of cognition should be considered in this population of patients, who may be involved in risky activities or have high work responsibilities.

Diagnosing mild cognitive impairment in Parkinson's disease: which tests perform best in the Italian population?

Mild cognitive impairment (MCI) is common in patients with Parkinson's disease (PD) and should be recognized early because it represents a predictor of PD-related dementia and worse disease course. Diagnostic criteria for PD-related MCI (PD-MCI) have recently been defined by a Movement Disorders Society (MDS) task force. The present study explored which neuropsychological tests perform best for a level II (i.e., comprehensive neuropsychological assessment) diagnosis of PD-MCI according to the MDS task force criteria in Italian-speaking PD patients. To this aim, we assessed a comprehensive 23-item neuropsychological battery, derived the best-performing 10-test battery (i.e., two tests per domain for each of the five cognitive domains), and explored its accuracy for diagnosing PD-MCI in comparison to the full battery in a group of PD patients. A secondary aim was to explore the role of this battery for subtyping PD-MCI according to single-domain vs. multiple-domain involvement. The 10-test battery showed 73% sensitivity and 100% specificity for diagnosing PD-MCI, and 69% sensitivity and 100% specificity for PD-MCI subtyping. In patients older than 70 years, we derived a slightly different 10-test battery with 84% sensitivity and 100% specificity for PD-MCI diagnosis, and 86% sensitivity and 100% specificity for PD-MCI subtyping. These 10-item neuropsychological batteries might represent a good trade-off between diagnostic accuracy and time of application, and their role in PD-MCI diagnosis and subtyping should be further explored in future prospective studies.

Screening for adult attention deficit/hyperactivity disorder in high-dose benzodiazepine dependent patients.

BACKGROUND AND OBJECTIVES: Adult attention-deficit/hyperactivity disorder (ADHD) is frequent in patients with substance use disorders (SUD), but information on its prevalence in high-dose benzodiazepine (BZD) dependence is lacking. We estimated the prevalence of adult ADHD in a group of treatment-seeking high-dose BZD dependent patients according to a valid screening tool, and explored the demographic and clinical characteristics of patients that screened positive for ADHD (ADHD+) in comparison to those that screened negative (ADHD-). METHODS: We prospectively recruited 167 consecutive patients with high-dose BZD dependence and screened them for adult ADHD with the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS-v1.1) Symptom Checklist Part A. We compared demographic and clinical characteristics in ADHD+ and ADHD- groups. RESULTS: Fifty-three patients (31.7% of the sample) were positive to adult ADHD screening. ADHD+ patients showed a significantly larger prevalence of poly-drug abuse than ADHD- ones. BZD formulation and active principle significantly differed between the two groups. The other clinical variables, including psychiatric comorbidity, as well as the demographic ones, did not differ in ADHD+ versus ADHD- comparison. DISCUSSION AND CONCLUSIONS: Adult ADHD may be common in treatment-seeking high-dose BZD dependent patients according to ASRS-v1.1 Symptom Checklist Part A. SCIENTIFIC SIGNIFICANCE: Screening for ADHD in this type of SUD with this questionnaire is quick and may offer useful information for prognosis and treatment. (Am J Addict 2017;26:610-614).

The effects of virtual reality environmental enrichments on craving to food in healthy volunteers.

RATIONALE: Environmental enrichment (EE) is a non-pharmacological approach that has been shown to be effective in reducing food-taking in rats. Studies in human volunteers are still in their infancy, given the difficulty to translate the complexity of EE in clinical practice. Virtual reality (VR) is a promising methodological approach, but no study has yet applied it to model and test EE in humans. OBJECTIVES: The present study is the first to assess the effects of virtual EE on craving for palatable food. METHODS: Eighty-one healthy volunteers (43 women) were divided into three groups: (i) exposure to a virtual EE (VR-EE), (ii) exposure to a virtual neutral environment (VR-NoEE), and (iii) without exposure to VR (No VR). Craving for palatable food at basal level and evoked by neutral and palatable food images was assessed before and after the VR simulation. Behavior during VR exposure and subjective measures related to the experience were also collected. RESULTS: VR-EE group showed a significantly greater decrease in pre-post craving difference compared to No VR for all assessments and at basal level compared to VR-NoEE. Interestingly, an inverse correlation between craving and deambulation in the VR simulation emerged in VR-EE group only. CONCLUSIONS: The study highlighted the feasibility of exposing human subjects to an EE as a virtual simulation. Virtual EE induced effects on basal craving for food that suggest the potential for further improvements of the protocol to extend its efficacy to palatable food cues.

Impact of Cognitive Rehabilitation on Cognitive and Functional Outcomes in Adult Cancer Survivors: A Systematic Review.

OBJECTIVES: This systematic review (PROSPERO CRD42021275421) synthesized evidence on the efficacy of cognitive rehabilitation on cognitive and functional outcomes in adult cancer survivors. METHODS: Articles were identified though PubMed/MEDLINE, EMBASE, PsycINFO, and Web of Science from inception through June 30, 2023. Studies included participants ≥18 years old, diagnosed with cancer. Primary outcomes were validated measures of subjective and objective cognition. Articles were dual reviewed for eligibility and data extraction. Risk of bias was assessed with the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields. RESULTS: The search yielded 3,811 articles; 65 full-text articles were reviewed; 53 articles (15 cognitive training, 14 strategy-based, 21 combinations, three inpatient rehabilitation), representing 52 unique studies, were included. Positive effects were observed in at least one objective cognitive measure in 93% of strategy training, 81% of cognitive training, 79% of combination rehabilitation interventions. Positive effects were observed in subjective cognition in 100% of strategy training, 55% of cognitive training, and 92% of combination interventions. Among studies with comparator groups, processing speed improved in 60% of cognitive training studies, while strategy training did not improve processing speed; otherwise, cognitive domain effects were similar between intervention types. Impact on functional outcomes was inconclusive. CONCLUSIONS: Cognitive rehabilitation appear beneficial for cancer-related cognitive impairment (CRCI). Differential effects on specific cognitive domains (eg, processing speed) and subjective cognition may exist between intervention types. IMPLICATIONS FOR NURSING PRACTICE: Nurses should increase patient and provider awareness of the benefits of cognitive rehabilitation for CRCI.

Non-invasive Brain Stimulation for Gambling Disorder: A Systematic Review.

Background: Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD. Objective: This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling. Methods: A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded. Results: A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies. Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed.

High-Dose Dependence and Cognitive Side Effects to Medical Prescription of Etizolam.

Introduction: The use of novel designer drugs has increased worldwide over the years. Etizolam is a designer benzodiazepine (BZD) that has raised concern because of its growing non-medical use, liability to tolerance and dependence, and related harms. Studies exploring the abuse liability and cognitive effects of etizolam outside the therapeutic doses are lacking. Aims: To explore the abuse liability of etizolam and the characteristics of patients affected by etizolam high-dose dependence in a nationwide tertiary referral addiction unit. To document the cognitive changes to etizolam high-dose use. Design and Methods: Sociodemographic and clinical data on subjects with etizolam high-dose use were retrospectively collected from a database of 1,293 patients consecutively admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZDs or Z-drugs dependence. Thorough neuropsychological testing explored the cognitive side effects of high-dose etizolam use. Results: We found eleven etizolam high-dose users, of which eight used etizolam only, and three used etizolam with other BZDs/zolpidem. All the patients were prescribed etizolam for medical reasons, i.e., anxiety and/or insomnia. Neuropsychological evaluation showed deficits of working memory, visuospatial memory and executive function in a 27-year-old woman who used etizolam 15 mg daily. Discussion: Our findings suggest that abuse and dependence liability of etizolam should be considered a public health and social problem. They offer preliminary evidence on the cognitive side effects of etizolam high-dose use. Conclusions: This report offers new information on the potential harms of etizolam in patients who are prescribed this drug for medical reasons.

Telemedicine and Virtual Reality for Cognitive Rehabilitation: A Roadmap for the COVID-19 Pandemic.

The current COVID-19 pandemic presents unprecedented new challenges to public health and medical care delivery. To control viral transmission, social distancing measures have been implemented all over the world, interrupting the access to routine medical care for many individuals with neurological diseases. Cognitive disorders are common in many neurological conditions, e.g., stroke, traumatic brain injury, Alzheimer's disease, and other types of dementia, Parkinson's disease and parkinsonian syndromes, and multiple sclerosis, and should be addressed by cognitive rehabilitation interventions. To be effective, cognitive rehabilitation programs must be intensive and prolonged over time; however, the current virus containment measures are hampering their implementation. Moreover, the reduced access to cognitive rehabilitation might worsen the relationship between the patient and the healthcare professional. Urgent measures to address issues connected to COVID-19 pandemic are, therefore, needed. Remote communication technologies are increasingly regarded as potential effective options to support health care interventions, including neurorehabilitation and cognitive rehabilitation. Among them, telemedicine, virtual reality, augmented reality, and serious games could be in the forefront of these efforts. We will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic. In particular, we will discuss issues related to their diffusion and propose a roadmap to address them. Methodological and technological improvements might lead to a paradigm shift to promote the delivery of cognitive rehabilitation to people with reduced mobility and in remote regions.

Detoxification Improves Multidomain Cognitive Dysfunction in High-Dose Benzodiazepine Abusers.

PURPOSE: High-dose benzodiazepines (BZDs) abuse has been documented to cause multidomain cognitive dysfunction. We explored whether cognitive abnormalities to high-dose BZD abuse might be reversed by detoxification with slow subcutaneous infusion of flumazenil. METHODS: We recruited 96 patients consecutively admitted to the Department of Internal Medicine, Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. After selection for inclusion and exclusion criteria, 50 patients (23 men, 27 women; age 42.7 ± 10.3 years) were included. They underwent a comprehensive neuropsychological battery to explore verbal memory, visuospatial memory, working memory, attention, and executive functions 28-30 days prior to admission for detoxification (T0) and at the end of detoxification, i.e., 7 days after admission (T1). A group of 50 healthy adults (24 men, 26 women; mean age 44.5 ± 12.8 years) matched for age, sex, and education served as controls. RESULTS: At T0, patients scored significantly worse than healthy controls in all the neuropsychological tests. Depression and anxiety scores were associated with impaired verbal memory at T0 in patients. T1-T0 comparison showed improved performances in all neuropsychological tests after the end of detoxification in patients. CONCLUSION: We confirmed that all neuropsychological domains were significantly and profoundly impaired by high-dose BZD abuse and documented that cognitive abnormalities improved after detoxification with slow subcutaneous infusion of flumazenil.

Internet Addiction and Related Clinical Problems: A Study on Italian Young Adults.

The considerable prominence of internet addiction (IA) in adolescence is at least partly explained by the limited knowledge thus far available on this complex phenomenon. In discussing IA, it is necessary to be aware that this is a construct for which there is still no clear definition in the literature. Nonetheless, its important clinical implications, as emerging in recent years, justify the lively interest of researchers in this new form of behavioral addiction. Over the years, studies have associated IA with numerous clinical problems. However, fewer studies have investigated what factors might mediate the relationship between IA and the different problems associated with it. Ours is one such study. The Italian version of the SCL-90 and the IAT were administered to a sample of almost 800 adolescents aged between 16 and 22 years. We found the presence of a significant association between IA and two variables: somatization (ß = 7.80; p < 0.001) and obsessive-compulsive symptoms (ß = 2.18; p < 0.05). In line with our hypothesis, the results showed that somatization predicted the relationship between obsessive-compulsive symptoms and IA (ß = -2.75; t = -3.55; p < 0.001), explaining 24.5% of its variance (ΔR 2 = 1.2%; F = 12.78; p < 0.01). In addition, simple slopes analyses revealed that, on reaching clinical significance (+1 SD), somatization showed higher moderation effects in the relationship between obsessive-compulsive symptoms and IA (ß = 6.13; t = 7.83; p < 0.001). These results appear to be of great interest due to the absence of similar evidence in the literature, and may open the way for further research in the IA field. Although the absence of studies in the literature does not allow us to offer an exhaustive explanation of these results, our study supports current addiction theories which emphasize the important function performed by the enteroceptive system, alongside the more cited reflexive and impulsive systems.

QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations.

The QTc interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. This marker is often prolonged in acute and chronic neurological conditions. The cause of the cerebrogenic QT prolongation remains unclear. The aim of the study was to analyze the relation between QTc interval and the degree of cognitive impairment and structural brain imaging changes in patients with dementia and mild cognitive impairment (MCI). To this aim, 269 patients were screened, of whom 61 met one or more exclusion criteria. The remaining 208 patients (56 control subjects, 44 patients with MCI, and 108 with dementia) were recruited. Eighty-five patients using drugs causing prolongation of QT interval were further excluded. The QT interval was measured manually in all 12 leads by a single blinded observer, assuming the longest QT value adjusted for heart rate by using the Bazett's formula. All patients underwent a structural brain imaging and the following measures were obtained: the bicaudate ratio and the periventricular hyperintensity and deep white matter hyperintensity using the modified Fazekas scale. Prolonged QTc interval was prevalent in 1) patients with dementia, especially in those with moderate-severe degree; 2) subjects with impairment of praxis and attention, low functional status, and behavioral symptoms; 3) patients with global and temporal atrophy and with higher scores on the Fazekas or leukoaraiosis scales. Degenerative and vascular processes might play a main role in QTc interval prolongation because of the damage to brain areas involved in the control of the autonomic cardiac nervous system.

Comparison between physical and cognitive treatment in patients with MCI and Alzheimer's disease.

Cognitive and physical activity treatments (CT and PT) are two non-pharmacological approaches frequently used in patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). The aim of this study was to compare CT and PT in these diseases. Eighty-seven patients were randomly assigned to CT (n=30), PT (n=27) or control group (CTRL; n=30) for 6 months. The global cognitive function was measured by Mini Mental State Examination (MMSE). Specific neuropsychological tests explored attention, memory, executive functions, behavioral disorders. Cardiovascular risk factors (CVD) were collected. All measures were performed before (T0), after treatments (T1), and at three-months follow-up (T2). MMSE did not change from T0 to T1 and T2 in patients assigned to PT and CT, while CTRL patients showed a decline MCI: -11.8%, AD: -16.2%). Between group differences (MCI vs AD) were not found at T1 and T2. Significant worsening was found for CTRL in MCI (T0- T1: P=.039; T0-T2: P<.001) and AD (T0-T1: P<.001; T0-T2: P<.001), and amelioration was found for CT in AD (T0-T2: P<.001). Attention, executive functions and behavioral disorders were unaffected by either PT or CT. Memory was increased in patients with MCI assigned to PT (+6.9%) and CT (+8.5%).. CVD were ameliorated in the PT group. CTRL patients of both groups, revealed significant decline in all functions and no between groups differences were detected. PT appear to ameliorate CVD. Although between groups differences were not found, results suggest a major retention in MCI compared with AD, suggesting that the latter might benefit better of constant rather than periodic treatments. This study confirms the positive effects of CT and PT in mitigating the cognitive decline in MCI and AD patients, and it is the first to demonstrate their similar effectiveness on maintaining cognitive function.

The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment.

Background: Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia. Aim: To review, with a narrative approach, current evidence on main NPTs for AD and dementia. Methods: PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers. Results: The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden. Conclusions: Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia.