COVID‐19 leads to severe respiratory problems, but also to long‐COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long‐COVID syndrome symptoms, especially brain fog, are ...similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.
We investigated the potential of machine learning for diagnostic classification in late-life major depression based on an advanced whole brain white matter segmentation framework. Twenty-six ...late-life depression and 12 never depressed individuals aged > 55 years, matched for age, MMSE, and education underwent brain diffusion tensor imaging and a multi-contrast, multi-atlas segmentation in MRIcloud. Fractional anisotropy volume, mean fractional anisotropy, trace, axial and radial diffusivity (RD) extracted from 146 white matter parcels for each subject were used to train and test the AdaBoost classifier using stratified 12-fold cross validation. Performance was evaluated using various measures. The statistical power of the classifier was assessed using label permutation test. Statistical analysis did not yield significant differences in DTI measures between the groups. The classifier achieved a balanced accuracy of 71% and an Area Under the Receiver Operator Characteristic Curve (ROC-AUC) of 0.81 by trace, and a balanced accuracy of 70% and a ROC-AUC of 0.80 by RD, in limbic, cortico-basal ganglia-thalamo-cortical loop, brainstem, external and internal capsules, callosal and cerebellar structures. Both indices shared important structures for classification, while fornix was the most important structure for classification by both indices. The classifier proved statistically significant, as trace and RD ROC-AUC scores after permutation were lower than those obtained with the actual data (P = 0.022 and P = 0.024, respectively). Similar results were obtained with the Gradient Boosting classifier, whereas the RBF-kernel Support Vector Machine with k-best feature selection did not exceed the chance level. Finally, AdaBoost significantly predicted the class using all features together. Limitations are discussed. The results encourage further investigation of the implemented methods for computer aided diagnostics and anatomically informed therapeutics.
Background:
Apathy is one of the most prevalent neuropsychiatric symptoms encountered in Alzheimer’s disease (AD) and may be an early sign in the development of dementia persisting over the disease ...course. It has been associated with poor disease outcome, impaired daily functioning, and significant caregiver distress. Early diagnosis and timely treatment of apathy in AD are of great importance. However, approved agents for apathy are still missing.
Methods:
Within this context, we conducted an extensive electronic search in the databases included in the National Library of Medicine, PsychInfo, and Google Scholar for studies that have investigated the effect of pharmacological treatments in apathy in AD. There were no limitations regarding study design and all care settings were considered for inclusion. Structured measures for level of evidence and study quality were employed to evaluate the results.
Results:
A total of 1,607 records were identified; 1,483 records remained after the removal of duplicates and were screened; 166 full-text articles were selected and assessed for eligibility and a remaining 90 unique studies and relevant reviews were included in the qualitative synthesis. Acetylcholinesterase inhibitors, gingko biloba, and methylphenidate were found to be successful in reducing apathy in patients with AD. Methodological heterogeneity in the studies and the small amount of studies where apathy was the primary outcome are limiting factors to assess for group effects.
Conclusions:
Pharmacological treatment of apathy in AD is an underexplored field. Standardized and systematic efforts are needed to establish a possible treatment benefit. Elucidating the pathophysiology of apathy and its components or subtypes will inform disease models and mechanistic drug studies that can quantify a benefit from specific agents for specific AD groups.
Abstract Introduction Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the ...literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. Methods The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. Results Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. Discussion Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention.
Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological ...interventions for apathy is greatly needed.
A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised.
In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects.
Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.
Apathy is one of the most frequent "behavioral and psychological signs and symptoms of dementia" (BPSD) encountered in Alzheimer's disease (AD). There is a growing interest in the early diagnosis of ...apathetic elderly patients in the community since apathy has been associated with reduced daily functioning, caregiver distress, and poor outcome. The generalization of neuroimaging techniques might be able to offer help in this domain.
Within this context we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for neuroimaging findings of apathy in AD.
Neuroimaging findings lend support to the notion that frontal-subcortical networks are involved in the occurrence of apathy in AD.
Longitudinal studies comparing patients and normal individuals might allow us to infer on the association between apathy and neurodegenerative diseases and what can brain imaging markers tell us about the characterization of this association, thus revealing disease patterns, helping to distinguish clinically distinct cognitive syndromes, and allowing predictions.
Νocebo Effect is known to induce adverse symptoms after negative expectations which can be manifested on a physical and psychological level. As 6th year medical students often face a wide range of ...clinical challenges and may be prone to negative expectations or beliefs affecting their pre-clinical and clinical success, we want to investigate how they are affected by the Nocebo Effect.
To investigate whether a nocebo effect can be induced when exposing final-year students to the clinical context of their training.
We used verbal suggestions as a nocebo mechanism and by using three tools, the Illness Attitude Scales, the Symptom Checklist-90, and the State-Trait Anxiety Inventory, we examined the difference in scores on measures of psychometric parameters in 33 participants who were on their 6th year medical and attended three clinics for the first time during their education. The administrations were given before and after attending each clinic, and negative verbal suggestions were given prior to the first administration. We also measured whether the overall number of clinics, had an effect on psychometric parameters.
The results revealed a significant increase in second administration overall in the three clinics in specific psychometric parameters but no statistically significant difference was observed after attending consecutive clinics.
Students reported the occurrence of adverse symptoms in the investigated psychometric parameters, which should be noted in order to avoid potential educational clinical failure.
Recently, cognitive deficits occurring in rheumatic diseases have attracted scientific attention. Cognitive symptoms in patients with Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) have not ...been thoroughly studied. This study aimed to assess cognitive function and its relationship with depressive symptoms in RA and SSc and compare it to mild neurocognitive disorder due to Alzheimer's disease (MiND) and to individuals without cognitive impairment.
Cognitive function and depressive symptoms were tapped with the Cognitive Telephone Screening Instrument plus (COGTEL+), the Serial Seven Test (SST), the Mini-Mental State Examination (MMSE) and the Geriatric Depression scale-15 (GDS), respectively. Statistical analyses included between groups-, correlation- and regression analyses. Demographic characteristics were considered in the regression models.
The study included 30 individuals with RA, 24 with SSc, 26 adults without cognitive impairment and 33 individuals with MiND. Lower performance in verbal short-term memory, concentration/attention, verbal fluency and MMSE in patients with RA compared to individuals without cognitive impairment was detected. Of note, performance on verbal fluency, concentration/attention, inductive reasoning and MMSE was lower in RA compared to MiND. Individuals with SSc performed worse in verbal fluency and in MMSE in comparison to adults without cognitive deficits. Verbal fluency deficits in SSc exceeded that in MiND. Performance on MMSE, COGTEL+, prospective memory, working memory, verbal fluency and concentration/attention was related to GDS scores, which did not vary across the groups.
Patients with RA and SSc encountered cognitive dysfunction, which partially pertains to depressive symptoms. Of note, the severity of cognitive dysfunction in many cases exceeded that of MiND.
Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used ...in AD patients, there is no conclusive evidence about their impact on the inflammatory response.
This study investigates peripheral proinflammatory cytokines (interferon gamma IFN-γ, tumor necrosis factor alpha TNF-α, and interleukins 1β IL-1β and 6 IL-6) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls. A subset of those drug-naïve AD patients, who were prescribed the AChEI donepezil, was followed-up for 6 months to investigate if donepezil suppresses proinflammatory cell-derived cytokine secretion.
Patients with AD showed higher levels of PBMC-derived proinflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) in comparison with healthy controls. On reexamination, previously drug-naïve AD patients who received donepezil treatment for 6 months displayed a decrease in cell-derived IFN-γ, TNF-α, IL-1β, and IL-6.
Proinflammatory PBMC-derived cytokines were increased in patients with AD in comparison with healthy controls and donepezil-reduced proinflammatory cytokines when examining drug-naïve AD patients before and after AChEI treatment.
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