Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.

OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D). DESIGN, SETTING AND PARTICIPANTS: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively. RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57). CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.

Anosmia predicts memory impairment in post-COVID-19 syndrome: results of a neuropsychological cohort study.

Recovered COVID-19 patients frequently suffer of cognitive disorders. Several etiopathogenetic mechanisms have been considered for the brain complications in COVID-19 but results are uncertain. Amongst them, an olfactory route to SARS-CoV-2 brain infection might explain cognitive and memory disturbances in post-COVID-19 patients, given the cooccurrence of anosmia and possible underlying limbic involvement. The aims of the study are to investigate cognition of patients with post-COVID-19 syndrome, and to find clinical factors predicting cognitive and memory impairments. 18 patients with post-COVID-19 syndrome underwent neuropsychological assessment and evaluation of clinical parameters. Stepwise regression analysis was used between clinical parameters as factors and cognitive global scores as dependent variables. Since only anosmia predicted memory performances, repeated measures ANOVA of memory scores was conducted between anosmic and non-anosmic patients. We found lack of association between clinical parameters and cognitive performances. Only anosmia was a good predictor for memory performances, with anosmic subjects showing a temporo-mesial amnesic profile. Our study shows novel findings of causal association between transient anosmia during COVID-19 and memory disorders with temporo-mesial dysfunction, probably sharing a common pathophysiological mechanism, and suggesting a possible SARS-CoV 2 infection of the limbic brain via the olfactory route. In contrast to previous studies, cognitive dysfunctions were not associated with respiratory distress, comorbidity, and depression.

Late-onset obsessive-compulsive disorder as the initial manifestation of possible behavioural variant Alzheimer's disease.

INTRODUCTION: A late-onset obsessive-compulsive disorder (OCD) might be a challenging diagnostic issue because of the overlapping with the dementia conditions more related to frontal lobe pathology. We aim to describe and investigate how this condition might represent the isolated long-lasting symptomatology of a frontal Alzheimer's disease (AD). METHODS: An elderly woman with normal cognitive status showed a subacute onset of OCD with contamination obsession and washing compulsion. We conducted neuropsychological assessments and neuroimaging examinations at the onset and at 3-years follow-up. RESULTS: At 3-years follow-up, the patient developed cognitive deterioration, frontal behavioural disorders and improvement of OCD. Cognitive assessment showed impairments of executive functions, episodic memory, and constructional apraxia, according to the involvement of fronto-mesial, temporal and parietal regions at neuroimaging. A clinical diagnosis of possible behavioural variant AD was assigned. CONCLUSION: A typical OCD might be the long-lasting initial manifestation of a possible behavioural variant AD due to dysfunctions of the anterior cingulate network.

Gold-Etched Silver Nanowire Endoscopy: Toward a Widely Accessible Platform for Surface-Enhanced Raman Scattering-Based Analysis in Living Cells.

Recently, our group introduced the use of silver nanowires (AgNWs) as novel non-invasive endoscopic probes for detecting intracellular Raman signals. This method, although innovative and promising, relies exclusively on the plasmonic waveguiding effect for signal enhancement. It, therefore, requires sophisticated operational tools and protocols, drastically limiting its applicability. Herein, an advanced strategy is offered to significantly enhance the performance of these endoscopic probes, making this approach widely accessible and versatile for cellular studies. By uniformly forming gold structures on the smooth AgNW surface via a galvanic replacement reaction, the density of the light coupling points along the whole probe surface is drastically increased, enabling high surface-enhanced Raman scattering (SERS) efficiency upon solely focusing the excitation light on the gold-etched AgNW. The applicability of these gold-etched AgNW probes for molecular sensing in cells is demonstrated by detecting site-specific and high-resolved SERS spectra of cell compartment-labeling dyes, namely, 4',6-diamidino-2-phenylindole in the nucleus and 3,3'-dioctadecyloxacarbocyanine on the membrane. The remarkable spectral sensitivity achieved provides essential structural information of the analytes, indicating the overall potential of the proposed approach for cellular studies of drug interactions with biomolecular items.

Adhesive capsulitis: A review for clinicians.

ABSTRACT: Adhesive capsulitis, a common primary care and orthopedic diagnosis often referred to as frozen shoulder, is a painful inflammatory process that leads to a mechanical block in active and passive range of shoulder motion. Risk factors include diabetes and thyroid dysfunction. Diagnosis is made based on physical examination, but can be augmented by diagnostic imaging. Nonsurgical management is the mainstay of treatment because the disease is self-limiting. However, some patients may need surgical intervention.

Progressive aphasia, apraxia of speech and agraphia in corticobasal degeneration: A 12-case series clinical and neuropsychological descriptive study.

BACKGROUND: Despite initial underreporting of language dysfunctions in corticobasal syndrome (CBS), aphasia is now recognized as a frequent feature of this disease. Aphasia in CBS seems clinically overlying to a non-fluent/agrammatic primary progressive aphasia (nfaPPA), which is also a clinical phenotype associated with corticobasal degeneration (CBD) pathology. However, the clinical features of aphasia in CBS still remain poorly delineated, resulting in misjudgements in the differential diagnosis from a PPA presentation of the disease. AIMS: To investigate the language disorders of this syndrome, also through a systematic examination of recoding skills (reading, written spelling and repetition) and articulatory disturbances, which have been rarely examined in previous studies. METHODS & PROCEDURES: We present a clinical and neuropsychological descriptive study of the language impairments in a case series of 12 aphasic patients with a clinical diagnosis of CBS. Language assessment was conducted by means of the Esame NeuroPsicologico dell'Afasia, a comprehensive Italian battery for language functions, the Token Test, and the Apraxia of Speech Rating Scale. OUTCOMES & RESULTS: The language profile of the patients showed a severe expressive language disorder, characterized by non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding and defective sentence repetition. Severe limb apraxia, visual-spatial deficit and alien hand syndrome were also present. Neuroimaging showed bilateral left asymmetric atrophies and hypometabolism in the frontal premotor, parietal posterior and temporal areas. CONCLUSIONS & IMPLICATIONS: These findings suggest that aphasia in CBS might present as a 'mixed PPA', instead of an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA, associated with AoS, stuttering and agraphia, which might be additional important cognitive markers for the clinical diagnosis of CBS and discriminating features of an nfaPPA presentation of a CBD. These results might also suggest specific intervention areas in the rehabilitation of patients with CBS. What this paper adds What is already known on the subject Language disorders in CBS patients usually present clinically overlying to an nfaPPA, which is also a clinical phenotype associated with CBD pathology, according to recent diagnostic criteria. However, the clinical features of aphasia in CBS still remain poorly delineated, and this raises difficulties and misjudgements for clinicians in the differential diagnosis from a PPA presentation of the disease. What this paper adds to existing knowledge This study shows that the language profile of our CBS patients was characterized by severe expressive language disorders, with non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding, and defective sentence repetition. These findings suggest that aphasia in CBS might present as a 'mixed PPA', rather than an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA associated with AoS, stuttering and agraphia. What are the potential or actual clinical implications of this work? These results suggest that AoS, stuttering and agraphia might be important additional cognitive markers for the clinical diagnosis of CBS, and discriminating features of an nfaPPA presentation of a CBD. The language disorders exhibited in the present study might also support speech and language therapists in targeting specific intervention areas in the rehabilitation of patients with CBS.

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis-Deepening Heterogeneity for a Personalized Therapy.

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray-Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.

The impact of sleep characteristics and epilepsy variables on memory performance in patients with focal seizures.

Disturbed sleep can negatively affect overnight memory retention as well as new learning the subsequent day. In healthy participants, positive associations between memory performance and sleep characteristics (e.g., time spent in slow-wave sleep [SWS]) have been detected. In a previous study, we found that SWS was much reduced in patients with focal seizures, but when correlations between memory complaints and various sleep characteristics were considered, the only significant relationship was with the time to onset of rapid eye movement (REM) sleep (i.e., REM latency). In this study, we investigated the relationships between sleep, epilepsy, and objective memory performance variables. Twenty-five patients with focal seizures had their memory tested while undergoing a two-day ambulatory electroencephalography (EEG). The sleep variables of interest were the percentage of time spent in SWS (%SWS) and REM latency. Epilepsy variables included the presence of (1) seizures, (2) interictal epileptiform discharges, and/or (3) hippocampal lesions as well as site of seizure origin (temporal vs extratemporal). Overnight retention (of autobiographical events, a story, and a complex geometric figure) and the ability to learn a word list on day 2 were the measures of memory. A significant positive correlation was found between word-list learning and %SWS during the previous night. A significant negative correlation was observed between REM latency and overnight retention of autobiographical events. Overnight retention scores for the story and geometric figure were not related to sleep characteristics but were negatively affected by the presence of epileptiform activity. Story retention was also worse for temporal lobe epilepsy (TLE) than for patients with extratemporal epilepsy (ETE). Those with hippocampal lesions were more impaired than those without lesions on word-list learning, autobiographical events' retention, and story retention. When multiple contributing factors were entered into regression analyses, %SWS was found to be the best predictor of subsequent word-list learning, whereas the presence of a hippocampal lesion was the best predictor of overnight retention of autobiographical events and a story. These findings provide further evidence of the ways in which particular sleep characteristics are associated with memory and suggest that treatment of sleep disturbances in patients with epilepsy might be helpful for improving their performance.

The clock drawing test as a screening tool in mild cognitive impairment and very mild dementia: a new brief method of scoring and normative data in the elderly.

many studies sustained that the clock drawing test (CDT) was not able to accurately detect people with CDR = 0.5. Other researchers have promoted the use of scoring approaches with multiple scales that rate quantitative and qualitative features of the production. Nevertheless, these scoring systems are complex and time-consuming. We propose a new brief CDT' scoring system in order to find a good measure for mild cognitive decline which is at the same time easy to administer. we enrolled 719 subjects: n. 181 with mild Alzheimer's disease (AD); n. 200 with amnesic mild cognitive impairment (MCI) and n. 338 healthy elderly subjects (C). our CDT-three-cluster scoring system demonstrated a good sensitivity and an excellent specificity to discriminate MCI subjects from normal elderly (76 and 84 %, respectively) and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer disease (CDR: 1) from normal elderly (91 and 90 %, respectively). We found that CDT' score = 1.30 discriminate people with MCI, whereas a score = 4.38 discriminate AD patients. The three-cluster-scoring-system demonstrated a good diagnostic accuracy, taking into account those error-items more predictive of cognitive decline: omission of numbers or hands, writing numbers or hands in a wrong position and writing numbers or hands in a different code. Our CDT' scoring system is very short and easy method which can be used also by non-specialist.

Disruption of learning and long-term retention of prose passages in patients with focal epilepsy.

Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippocampus become important for recall.

Normative data for the ACE-R in an Italian population sample.

The Addenbrooke's Cognitive Examination Revised (ACE-R) is a brief cognitive screening instrument also proposed to detect mild cognitive impairment, a high-risk condition for Alzheimer's disease and other forms of dementia. In this study, we report normative data on the ACE-R-Italian version, collected on a sample of 264 Italian healthy subjects aging between 60 and 93 years, and with a formal education from 1 to 19 years. The global normal cognition was established in accordance with the Italian version of the Mini-Mental State Examination score and with exclusion criteria derived by a consensus process. Linear regression analysis was performed to evaluate the effect of age, gender, and education on the ACE-R total performance score. We provide correction grids to adjust raw scores and equivalent scores with cut-off value to allow comparison between ACE-R performance and others neuropsychological test scores that can be administered to the same subject.

Benefit from anthracyclines in relation to biological profiles in early breast cancer.

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N- or 1-3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER-, PgR-, HER2-), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17-0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10-0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER-, PgR-) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ (2) = 6.72, P = 0.009). In triple unfavorable (ER-, PgR-, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26-0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15-0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors.

Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity.

Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer's disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be "subjective," but rather a specific and defined clinical entity.

SERS Endoscopy for Monitoring Intracellular Drug Dynamics.

Understanding the dynamics and distribution of medicinal drugs in living cells is essential for the design and discovery of treatments. The tools available for revealing this information are, however, extremely limited. Here, we report the application of surface-enhanced Raman scattering (SERS) endoscopy, using plasmonic nanowires as SERS probes, to monitor the intracellular fate and dynamics of a common chemo-drug, doxorubicin, in A549 cancer cells. The unique spatio-temporal resolution of this technique reveals unprecedented information on the mode of action of doxorubicin: its localization in the nucleus, its complexation with medium components, and its intercalation with DNA as a function of time. Notably, we were able to discriminate these factors for the direct administration of doxorubicin or the use of a doxorubicin delivery system. The results reported here show that SERS endoscopy may have an important future role in medicinal chemistry for studying the dynamics and mechanism of action of drugs in cells.

Fetal variant of circle of the Willis and bilateral symmetrical parietal stroke.

We described a rare case in which a congenital abnormal vascular structure associated with mild hyperhomocysteinemia could have caused an ischemic stroke, with an unusual localization in the border-zone of MCA and PCA. We think that the lack of compensatory flow distribution from the right vertebral artery and the right posterior communicating artery probably determined the bilateral ischemic lesions in a patient, who possibly had hypotensive crisis.

Dural Arteriovenous Fistula as a Reversible Cause of Progressive Parkinsonism and Dementia: A Case Report.

A dural arteriovenous fistula (DAVF) is an abnormal direct connection between an intracranial artery and the dural venous sinus. In rare cases, DAVF might show rapidly progressive dementia onset with extrapyramidal signs, often misdiagnosed as Parkinson disease or vascular parkinsonism and, therefore, pharmacological treatments are ineffective. Here, we report the case of 84-year-old man with rapidly progressive parkinsonism and dementia who was initially treated with levodopa without any improvement. Approximately 8 months following the symptom onset, a magnetic resonance (MR) imaging of the brain revealed bilateral and symmetrical hyperintensity of the white matter on both cerebral hemispheres on T2-weighted images. Three-dimensional and post-contrast T1-weighted images showed a subtentorial ovalar area with venous drainage alteration, and hypertrophic left occipital artery direct to venous sac. The angiography study confirmed a diagnosis of DAVF. Endovascular treatment by cook pressure technique successfully provided fistula obliteration. The patient rapidly recovered after the endovascular treatment, with restitutio ad integrum of cognitive functioning and resolution of extrapyramidal syndrome. Approximately 1 year after the endovascular treatment, a brain MR scan with angiogram-MR sequences showed almost complete disappearance of white matter alterations on both cerebral hemispheres, and normal visualization of venous system.

Improving Amnesia Diagnostic Accuracy with RAVLT Single Scores and Composite Indices: Italian Normative Data.

OBJECTIVE: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used verbal memory measure that provides scores for different aspects of memory. It involves repeated auditory presentation and recall of a 15-item word list (List A) followed by presentation and recall of a distractor list (List B) and then un-cued immediate and delayed recalls (at 15 min and 1 week) of List A as well as recognition testing. Aims of this study are to provide Italian normative data for certain RAVLT Scores and Composite Indices to improve the diagnostic accuracy of the test in clinical settings and to provide further evidence on how RAVLT can differentiate different amnesia profiles due to focal lesions. METHODS: We enrolled 440 healthy participants and RAVLT Single Scores and Composite Indices have been analyzed by means of multiple regression to verify the influence of age, education, and gender. RESULTS: We computed the best linear models with RAVLT Single Scores and Composite Indices, as dependent variables, and the most suitable transformation of independent variables. By reversing the signs of the regression coefficients, the adjustment factors for each level of age and, if needed, education and gender have been computed and the adjusted scores have been standardized into Equivalent Scores. CONCLUSION: Using these standardized measures, we differentiate three profiles of amnesia due to selective hippocampal sclerosis with severe encoding deficit, fornix lesions with source memory problems, and temporal lobe epilepsy with consolidation failure.

Beyond the bipolar disorder diagnosis: Hypothalamus and its network damage in determining neuropsychiatric and Korsakoff-like memory disorders.

Craniopharyngiomas (CP's) are hypothalamic tumors often associated with psychological disorders. Nevertheless, its diagnosis is still challenging when psychiatric disorders are not associated with any other neurological symptoms. This single-case study describes a patient with a history of bipolar disorder before a diagnosis of a large CP arising the sellar and suprasellar region was posed. At the time of the present study the patient showed emotional/behavioral disorders and Korsakoff-like amnesia, that completely recovered after surgical resection of the tumor. This is one of those few cases described in literature, who presented cognitive/behavioral disorders because the compression of the diencephalic structures due to CP mass effect. This case offers further evidence on the functional neuroanatomy of the hypothalamus and its pathways.

Rotigotine effect in prolonged disturbance of consciousness. Brief report of two cases.

Two patients with post-coma reactivation deficiency who showed a "dramatic" response to rotigotine therapy are described. They had suffered from prolonged coma due to lesions in the mesencephalic ventral tegmental area. The authors believe that rotigotine effect in these cases could be due to restoration of dopaminergic transmission in medial frontal areas previously "de-afferented" from the lesions. Some comatous patients may experience a prolonged difficulty in recovering a normal state of consciousness. This phenomenon may be due to dysfunction of amynergic activating pathways connecting brainstem to the frontal cerebral cortex. In particular, dysfunction of dopaminergic pathways from the mesencephalon to the frontal cortical areas may be responsible for clinical pictures characterized by preserved alertness and total loss of interactions with the surrounding environment; the so called "waking coma" cases.