Functional Disorders Research Articles

The Spectrum Between Catatonia and Functional Neurologic Disorder Superimposed on Post-Infectious Encephalitis in a Marine Recruit.

Catatonia, a neuropsychiatric condition characterized by abnormal speech, volition, and movement, is primarily thought of as a symptom of a primary psychiatric pathology, but there are a variety of non-psychiatric medical conditions that must be considered. As a result of symptomatic complexity and the wide range of differential diagnoses, catatonia-like symptoms can cloud the clinical evaluation and complicate treatment regimens. Within the realm of catatonic-like diagnoses is functional neurological disorder because of its vast range of potential presentations. Functional neurologic disorder can be diagnosed by evidence of incompatibility between neurologic symptoms and recognized neurological or medical conditions. Clinical uncertainty is further intensified in the presence of co-morbid medical etiologies because of inability to neatly delegate symptoms to a specific diagnosis. The blurred spectrum between catatonia and functional neurologic disorder is highlighted in this patient's complex clinical presentation while being further obscured in the setting of a possible overlying encephalitis exacerbating the presentation. This case report presents a unique case of a Marine recruit whose inconsistent catatonic symptoms caused diagnostic uncertainty and were ultimately decided to have neurologic and psychiatric contributions, highlighting that diagnoses are not mutually exclusive and should be continually re-assessed as new data become available. This report also showcases the distinctiveness of U.S. Marine culture and possible physical manifestations because of imposed psychological stress.

Exploring the Role of Homeopathic Intervention in Post-COVID Functional Gastrointestinal Disorders: A Case Series of 12 Patient Profiles.

In the last 2 years of the pandemic, a wide range of cases of post-COVID functional gastrointestinal disorders (PC-FGIDs) has been reported. This case series aimed to investigate the role of homeopathic intervention in the treatment of PC-FGIDs. This is a retrospective analysis of the clinical data of individuals who had suffered from PC-FGIDs that were diagnosed based on clinical symptoms using the Gastrointestinal Symptoms Rating Scale (GSRS) and treated exclusively with individualized homeopathic medicines. Cases that had undergone regular monthly assessment using the GSRS and had a Post-COVID-19 Functional Status (PCFS) score for up to 3 months were considered. Thirty cases were screened and twelve were included according to the study criteria. The mean age of seven women and five men was 36 years. GSRS and PCFS scores showed marked improvement in each of 10 cases within the 3-month treatment period. Homeopathic intervention proved beneficial in 10 of 12 patients with PC-FGIDs. The findings may help researchers plan future controlled clinical studies in this field.

Novel approaches to psoriatic onychopathy diagnostics and treatment

Psoriasis is one of the most important problems in the clinical practice of a dermatovenereologist. In addition to damage of the skin and joints, the nail involvement is often seen in psoriatic patients. Despite its wide prevalence and significant impact on the quality of life, psoriatic onychopathy is discussed relatively rare. A change in the nails may indicate early alterations in the small joints of the palms, еthat foster to suspect psoriatic arthritis at an earlier time. Besides, the severity of nails lesions determined on the base of the NAPSI index correlates directly with the severity of pain in enthesitis. Nails damage in psoriasis does not entail persistent functional disorders, but significantly affects the patient’s quality of life due to a visible cosmetic defect. In addition, psoriatic onychopathy is difficult to treat. The use of topical agents is impractical, and systemic therapy gives a weak clinical response over a longer period. Even in the absence of a pathological process on the skin, nail psoriasis may persist much longer, which causes significant discomfort to patients. The study of pathomorphological aspects and mechanisms of nail psoriasis development will allow to disover a new methods for the effective treatment of psoriatic onychopathy.

'Positive' inter-ictal clinical signs of functional neurological disorders are found in patients with functional dissociative seizures.

Prior studies highlighted the high diagnostic specificity (ranging from 92% to 100%) of clinical signs observed in functional neurological disorders (FNDs). However, these signs are rarely looked for by epileptologists when trying to distinguish between functional dissociative seizure (FDS) and epileptic seizure. The aim of this study was to determine the prevalence of inter-ictal clinical signs of FND in a cohort of patients with probable FDS. The secondary objective was to compare the prevalence of inter-ictal FND clinical signs in FDS patients with age- and gender-matched epileptic patients without FDS. Patients diagnosed with FDS seen at two tertiary care centres and epileptic outpatients were included in the study. Each patient underwent a physical examination, searching for inter-ictal clinical signs of FND. In the FDS group, 79% of patients presented at least one sign of FND, compared to 16.6% of patients with epilepsy (p < 0.001). Moreover, 66.6% of FDS patients presented three or more FND signs, whereas only 4.1% of epileptic patients did (p < 0.001). The median number of FND clinical signs in the FDS group was four (SD 1.7; 5.5). Using the threshold of three signs or more, the specificity of detecting three or more FND signs was 83.3%, with a sensitivity of 79.2%. Inter-ictal clinical signs of FND are present in patients with FDS and should be looked for during neurological examination.

A systematic review of preclinical studies targeted toward the management of co-existing functional gastrointestinal disorders, stress, and gut dysbiosis.

Modern dietary habits and stressed lifestyle have escalated the tendency to develop functional gastrointestinal disorders (FGIDs) through alteration in the gut-brain-microbiome axis. Clinical practices use symptomatic treatments, neglect root causes, and prolong distress in patients. The past decade has seen the evolution of various interventions to attenuate FGIDs. But clinical translation of such studies is very rare mostly due to lack of awareness. The aim of this review is to meticulously integrate different studies and bridge this knowledge gap. Literature between 2013 and 2023 was retrieved from PubMed, ProQuest, and Web of Science. The data was extracted based on the PRISMA guidelines and using the SYRCLE's risk of bias and the Cochrane Risk of Bias tools, quality assessment was performed. The review has highlighted molecular insights into the coexistence of FGIDs, stress, and gut dysbiosis. Furthermore, novel interventions focusing on diet, probiotics, herbal formulations, and phytoconstituents were explored which mostly had a multitargeted approach for the management of the diseases. Scientific literature implied positive interactions between the interventions and the gut microbiome by increasing the relative abundance of beneficial bacteria and reducing stress-related hormones. Moreover, the interventions reduced intestinal inflammation and regulated the expression of epithelial tight junction proteins in different in vivo models. This systematic review delves deep into the preclinical interventions to manage coexisting FGIDs, stress, and gut dysbiosis. However, in most of the discussed studies, long-term risks and toxicity profile of the interventions are lacking. So, it is necessary to highlight them for improved clinical outcomes.

Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy

BackgroundAdvanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients.Materials and methodsThis study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared.ResultsThe median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05).ConclusionGEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment.Trial registration numberNCT02635971.Date of registration21/12/2015.

Beyond movement: Headache in patients with functional movement disorders.

To evaluate headache comorbidity in a cohort of patients with functional movement disorders by assessing the prevalence, clinical characteristics, and temporal relationship of headache with the onset of functional symptoms. Functional movement disorders are common and potentially treatable. Although headache is frequent in these patients, few studies have evaluated their headache features. This observational cohort study included consecutive patients with functional movement disorders evaluated in our Functional Movement Disorders Unit between October 2021 and November 2022. Clinical and demographic features from clinical charts were reviewed, and patients completed a self-administered questionnaire designed by the authors that included headache characteristics, disease duration, treatments received, and the Headache Impact Test-6. Headache type was classified as per the Classification of Headache Disorders, third edition (ICHD-3). A total of 51 patients with functional movement disorders were included. Of those, 40 (78%) reported having recurrent headache. Headache intensity was moderate-severe in 33/40 (83%), and about two-thirds experienced headache >9 days/month. Disability secondary to headache was high (median [interquartile range] Headache Impact Test-6 score 62 [49-66]). Based on the ICHD-3, 23/40 (58%) of patients with headache met the criteria for migraine or probable migraine, 11/40 (27%) for tension-type headache, two of 40 (5%) for new daily persistent headache, and one of 40 (3%) for primary exercise headache, while three of 40 (7%) were unclassifiable. The onset of headache occurred before the functional movement disorder in 28/40 (70%), after the functional movement disorder in five of 40 (12%), and simultaneously in six of 40 (15%). In this last group, four of the six (67%) patients described a daily headache from the onset, and two met the criteria for new daily persistent headache. Headache is a frequent condition in patients with functional movement disorders and an additional burden of disability beyond their motor symptoms. We found that, besides migraine and tension-type headache, new daily persistent headache may be a comorbid phenotype in patients with functional movement disorders and should be further studied in larger prospective studies.

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

Peripherally induced movement disorders in the stomatognathic system after oral surgical or dental procedures.

Peripherally induced movement disorders (PIMD) are hyperkinetic movement disorders that can occur after injury to a part of the body. This study aimed to identify PIMD in the stomatognathic system following dental or oral surgical procedures. A total of 229 patients with PIMD (144 women and 85 men; mean age: 53.4 years) triggered by oral surgical or dental interventions were evaluated retrospectively. The average latency between the procedures and onset of PIMD was 14.3 days. Oral surgery (40.2%), including tooth extraction, trauma treatment, and other surgical procedures, was the most frequent trigger of PIMD. This was followed by general dental treatment, including periodontal, endodontic, and restorative procedures (36.7%), prosthetic treatment (19.7%), and orthodontic treatment (3.5%). PIMD consisted of oromandibular dystonia (73.8%), functional (psychogenic) movement disorders (11.4%), orolingual dyskinesia (7.9%), and hemimasticatory spasms (5.7%). These results suggest that even minor alterations in normal anatomy or physiology after dental procedures may result in PIMD in predisposing patients. Dental professionals should be aware that although infrequently, PIMD can develop after various dental treatments. If such symptoms precipitate, the attending physician should properly explain them to the patient and provide appropriate treatment or consultation with a movement disorder specialist.

Translation process of the tested Rome IV diagnostic questionnaire for functional gastrointestinal disorders into Saudi-Arabian Arabic: A mixed-methods approach

Translation process of the tested Rome IV diagnostic questionnaire for functional gastrointestinal disorders into Saudi-Arabian Arabic: A mixed-methods approach

Thyroid scintigraphy: establishing a clinically useful normal range for 99mTc pertechnetate uptake.

This study aims to establish a normal range for the thyroid uptake derived from 99mTc pertechnetate scans. In particular, variations of uptake with TSH stimulation and other factors such as urinary iodine concentration are taken into account and compared with the calculation of a raw uptake value. Clinical multicentric (center A, B and C) prospective study on 125 consecutive healthy patients undergoing thyroid scans for thyroid nodules. Normal functional thyroid status was assured by normal TSH, normal thyroid size, no thyroid antibodies and no symptoms of thyroid functional disorders. Calculations of raw Tc-uptake (uptake) and modified uptake values regarding current TSH value (uptakeTSH1), urinary iodine concentration (uptakeTSH1&uic), gland volume, age, smoking status, weight and tissue thickness ventral to the thyroid were performed. There is a positive correlation of thyroid uptake with TSH allowing for the calculation of a normalized uptake value (uptakeTSH1). The normal range for uptakeTSH1 compares favourable to that for raw uptake in that it yields a clear distinction from thyroid functional disorders. The additional normalization for urinary iodine concentration (uptakeTSH1&uic) may even improve the distinctive power whereas further normalizations such as for gland volume, age and others are not warranted by this study. The 95% CI of uptakeTSH1 for sites A, A&B, and A&B&C were 0.21%-2.06%, 0.22%-2.38% and 0.24%-2.40%. A normal range for the thyroid uptake can be established with respect to the current TSH stimulation. This normalization (uptakeTSH1) overcomes the drawback of raw uptake by yielding a clinically useful parameter with obviously high distinctive power against functional thyroid disorders.

Making meaning: The experience of Shared Individual Formulation Therapy in adults with functional neurological disorder

Making meaning: The experience of Shared Individual Formulation Therapy in adults with functional neurological disorder

Lactiplantibacillus plantarum Regulates Intestinal Physiology and Enteric Neurons in IBS through Microbial Tryptophan Metabolites.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by visceral pain and gut dysmotility. However, the specific mechanisms by which Lactobacillus strains relieve IBS remain unclear. Here, we screened Lactobacillus strains from traditional Chinese fermented foods with potential IBS-alleviating properties through in vitro and in vivo experiments. We demonstrated that Lactiplantibacillus plantarum D266 (Lp D266) administration effectively modulates intestinal peristalsis, enteric neurons, visceral hypersensitivity, colonic inflammation, gut barrier function, and mast cell activation. Additionally, Lp D266 shapes gut microbiota and enhances tryptophan (Trp) metabolism, thus activating the aryl hydrocarbon receptor (AhR) and subsequently enhancing IL-22 production to maintain gut homeostasis. Mechanistically, Lp D266 potentially modulates colonic physiology and enteric neurons by microbial tryptophan metabolites. Further, our study indicates that combining Lp D266 with Trp synergistically ameliorates IBS symptoms. Together, our experiments identify the therapeutic efficacy of tryptophan-catabolizing Lp D266 in regulating gut physiology and enteric neurons, providing new insights into the development of probiotic-mediated nutritional intervention for IBS management.

Diagnosis and Treatment of Temporomandibular Disorders

Temporomandibulr disorders(TMDs) is a comprehensive term that encompasses functional disorders affecting the masticatory system, including the temporomandibular joint and masticatory muscles. This term contains various diseases, and the presence of multiple etiologies makes the diagnosis and treatment of TMDs more complex. Therefore, this paper aims to explore the classification and diagnosis of TMDs, with a focus on the DC/TMD. Additionally, this paper investigated the definitive treatment and supportive therapy for TMDs.

PENGARUH DZIKIR TERHADAP KECEMASAN DAN KOPING RELIGIUS PASIEN HEMODIALISIS

Chronic Kidney Failure is a progressive and irreversible kidney function disorder where the body is unable to maintain fluid and electrolyte balance, resulting in uremia. In general, cases of chronic kidney failure undergoing hemodialysis are increasing every year, especially in developing countries. The anxiety and decreased coping experienced by patients suffering from chronic kidney failure undergoing hemodialysis is due to a lack of support and enthusiasm from the family, funding for treatment and costs to meet living needs.A literature search was carried out based on articles published between 2018-2023 according to the inclusion and exclusion criteria that had been determined using 1 data base, namely Google Schoolar. This literature search uses the PRISMA guideline in carrying out the screening process. From the search results, 200 articles were obtained. After carrying out the screening process, there were 8 articles that met the criteria and will be analyzed.Based on a study of 8 pieces of literature, it was found that the hemodialysis process affects clients' religious anxiety and coping.From the results of a literature review of 8 journals, it was found that dhikr was able to reduce anxiety levels because the client felt calmer Keywords: Dhikr, anxiety, religious coping

Clinical Characteristics of Patients with Primary and Secondary Fibromyalgia in Bulgaria

Fibromyalgia (FM) is characterized by a chronic widespread pain, general fatigue, anxiety, depression, sleep disturbances and functional disorders. FM affects both women and men in 9:1 to 20:1 ratio. The purpose of this clinical study is to analyze clinical manifestations in patients with primary and secondary fibromyalgia. Eighty-three patients with primary FM, 39 patients with FM and osteoarthritis (OA), 23 patients with FM and systemic lupus erythematosus (SLE), 27 patients with SLE, and 36 healthy subjects were included. The present study compared chronic pain, fatigue, depression and anxiety in patients with primary FM, patients with SLE, FM + OA, FM + SLE and healthy subjects. Based on the 2016 criteria for number of chronic widespread pain areas, there is a statistically significant difference of the control group compared to the patients with primary FM (p = 0.001), FM + OA (p = 0.001), FM + SLE (p = 0.001), SLE (p = 0.001). Based on the MFIS fatigue scale, the chronic fatigue is a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.004), FM + OA (p = 0.02), FM + SLE (p = 0.001). Based on the HADS clinical parameter, anxiety and depression are a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.01), FM + OA (p = 0.01), FM + SLE (p = 0.01), and no difference in patients with SLE (p = 0.77). The comparison between the patient groups is important to evaluate the disease activity and the treatment to be recommended.

Long COVID Is Not a Functional Neurologic Disorder

Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID. The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID. We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.

The effect of neurotransmitters on the course of functional gastrointestinal disorders associated with emotional volitional disturbances caused by stress in children

Background. The medico-social significance of functional gastrointestinal disorders (FGID) in children is due to their prevalence and impact on the quality of life of patients. According to the biopsychosocial model, FGID are heterogeneous diseases that arise as a result of a complex interaction of biological, psychoemotional, and psychosocial factors. Objective: based on the gene­ralization of available literature data, to highlight the influence of serotonin and melatonin neurotransmitters on the course of FGIR associated with emotional volitional disturbances caused by stress in children. Materials and methods. Modern domestic and international scientific literature on the influence of serotonin and melatonin on the course of FGIR associated with emotional volitional disturbances caused by stress in children was reviewed and analyzed. To search for literary sources, the Scopus, PubMed, ResearchGate, Wiley Online Library, and Google Scholar databases were studied for 2016–2024, a total of 98 sources. Results. Modern etiopathogenetic factors for the occurrence of FGIR in children are described, with the key components of their biopsychosocial model highligh­ted. The influence of stressors on the development of mental disorders in children with FGIR, in particular emotional and volitional changes, is considered. We have demonstrated the role of serotonin and melatonin in the regulation of mood, emotions, sleep, beha­vior, anxiety, depression, etc. The importance of these neurotransmitters in the occurrence of gastrointestinal symptoms in FGIR is highlighted with modern approaches to the management of children with FGIR associated with emotional volitional disturbances caused by stress being considered. A promising therapeutic direction is identified — the use of supplements of certain neurotransmitters (in particular, serotonin and melatonin) in children with this pathology. Conclusions. The analyzed literature data demonstrate the heterogeneity of FGIR in children and the importance of stressors in their development. Neurotransmitters play a significant role in the formation of the response to stress and the course of FGIR associated with emotional volitional disturbances caused by stress in children. Data on the effectiveness of serotonin and melatonin supplementation in children with FGIR are few, so there is a need for further research on this issue in order to improve the effectiveness of treatment and the quality of life of these patients.

The combination of L-menthol and caraway oil does not affect gastric function but increases hunger in healthy subjects.

The heterogeneous character of functional gastrointestinal disorders, recently renamed into disorders of gut-brain interaction, makes finding effective treatment options challenging. Compared to synthetic drugs, phytotherapy can have broader pharmacological effects and is often better tolerated. This study aimed to investigate the effect of peppermint oil and caraway oil (POCO) on gastric function and symptom levels in 32 healthy subjects in a single-blinded, placebo-controlled, randomized, parallel design. Gastric emptying rate was assessed using a 13C-breath test. Intragastric pressure was measured using high-resolution manometry in fasted state and during intragastric infusion of a nutrient drink (350 mL or until full satiation). GI symptoms were rated on a 100 mm VAS. Data were analyzed using linear mixed models. POCO had no effect on intragastric pressure in fasted or fed state (p > 0.08 for all). No significant differences in gastric emptying rate were observed (p = 0.54). In the fasted state, a stronger increase in hunger and decrease in satiety were observed following POCO (p = 0.016 and p = 0.008, respectively). No differences in hunger and satiety were observed in the fed state (p > 0.31 for all). POCO induced less epigastric burning, bloating, and fullness (p < 0.05 for all). Acute POCO administration did not affect gastric function in healthy subjects, but increased fasted hunger ratings. The effects of POCO on gastric function and hunger sensations in patients with disorders of gut-brain interaction, and the contribution to symptom improvement, needs to be elucidated in future studies.

Subjective cognitive decline: Memory complaints, cognitive awareness, and metacognition.

Cognitive complaints are common in elderly subjects and are a frequent reason for referral to memory clinics. If the complaints are not associated with objective cognitive impairment, the condition is labelled subjective cognitive decline (SCD). SCD is often considered as a stage antedating objective impairment, and an at-risk condition for subsequent dementia. Recent large-scale studies indicate that a significantly increased risk of clinical progression in subjects with SCD is associated with positivity for Alzheimer's disease (AD) biomarkers, a finding supporting the notion that SCD can be due to different mechanisms not associated with neurodegeneration, including functional cognitive disorders. In this paper we present a selective review of research on the relations among SCD, cognitive awareness, and metacognitive abilities. We propose that longitudinal studies of metacognitive efficiency in SCD may provide useful cues about the risk of progression to dementia and the possible presence of a functional cognitive disorder, with different implications for the management of this prevalent aging-related condition. HIGHLIGHTS: Subjective cognitive decline (SCD), a common cause of referral to memory clinics, can be due to multiple conditions. The predictive value of SCD for progression to Alzheimer's disease (AD) dementia is high in association with AD biomarker positivity. The awareness of cognitive decline is the mechanism responsible for the emergence of SCD and metacognition is the underlying neuropsychological function. The awareness of cognitive decline in clinical patients is usually assessed comparing an informant rating to the patient self-assessment, a method that can be affected by informant bias. While there is strong evidence that awareness starts to decline with the onset of objective cognitive impairment, progressively leading to the anosognosia of AD, the status of metacognitive efficiency in SCD needs to be further investigated. Quantitative, performance-based indexes of metacognitive efficiency may contribute both to the assessment of progression risk and to the management of subjects with functional cognitive disorders.