Behavioral Disorders of Spatial Cognition in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease (The BDSC-MCI Project): Ecological Validity of the Corsi Learning Suvra-Span Test.

BACKGROUND: Spatial navigation deficits are reported as early symptoms of Alzheimer's disease (AD) alongside episodic memory ones. The aim of the present study was to ascertain whether neuropsychological deficits of visuospatial long-term memory can predict behavioral alterations during the navigation of older adults in novel urban environments along the normal aging-dementia continuum of the Alzheimer's type. METHODS: A total of 24 community-dwelling patients with Mild Cognitive Impairment (MCI) due to AD, 27 individuals with subjective cognitive decline (SCD), and 21 healthy controls were assessed in terms of their sequential egocentric and allocentric navigation abilities by using a modified version of the Detour Navigation Test, and neuropsychologically tested by the Corsi learning suvra-span (CLSS) test. Generalized linear models were adopted to verify whether the scores obtained by the three groups in the CLSS test predicted wrong turns and moments of hesitation during the navigation task, with the results presented as topographical disorientation scores. RESULTS: Higher scores in the CLSS test predicted fewer wrong turns (b = -0.05; z = -2.91; p = 0.004; net of between-groups differences) and moments of hesitation for patients with MCI due to AD (b = -0.14; z = -2.43; p = 0.015), and individuals with SCD (b = -0.17; z = -3.85; p < 0.001). CONCLUSIONS: Since the CLSS test has been reported to be a reliable measure of ecological navigational abilities in the progression towards AD dementia, we recommend its use in clinical practice and highlight implications for future research.

Verbal learning in frontal patients: area 9 is critical for employing semantic strategies.

INTRODUCTION: Learning is a long-term memory process heavily influenced by the control processes implemented by working memory, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. AIM: The aim of this study is to investigate the verbal learning strategies of patients affected by a tumor in the left frontal lobe to highlight the role of area 9. METHOD: Ten patients with frontal low-grade gliomas and ten healthy control subjects, matched for age, sex and education, were recruited and then evaluated with a two-part verbal learning test: multi-trial word list learning in free recall, and multi-trial word list learning preceded by an explicit semantic strategy cue. Frontal patients were divided into two groups: those either with frontal lesions involving or sparing area 9. RESULTS: In comparison to healthy control subjects, frontal patients with lesions involving area 9 memorized fewer words and displayed difficulty in using semantic strategies. When the strategy was suggested by the examiner, their performance improved, but to a lesser extent than the healthy control. Conversely, frontal patients with lesions sparing area 9 showed similar results to healthy control subjects. CONCLUSION: The results suggested that, while the identification of the categorical criterion requires the integrity of the entire dorsolateral prefrontal area, only area 9, and not the surrounding areas, could be responsible for the effective use of semantic strategies in learning tasks.

Psychometrics and diagnostics of the Italian version of the Alternate Verbal Fluency Battery (AVFB) in non-demented Parkinson's disease patients.

BACKGROUND: Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. METHODS: N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB-which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. RESULTS: The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. DISCUSSION: In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research.

One-Dimensional and Two-Dimensional Zn(II) Coordination Polymers with Ditopic Imidazo[1,5-a]pyridine: A Structural and Computational Study.

Zn(II) coordination polymers are being increasingly studied for their stability and properties. Similarly, there is a growing interest in imidazo[1,5-a]pyridine derivatives, which show great potential in luminescence and pharmaceutical applications. In this work, we successfully synthesized and crystallized three new coordination polymers, using Zn(II) as the metallic node, dicarboxylic acids of different length and nature as linkers, and a linear ditopic imidazo[1,5-a]pyridine derivative, to explore the role of this molecule as a propagator of the dimensionality of the structure or as an ancillary ligand. Our work demonstrates the structural capability of imidazo[1,5-a]pyridines in an unexplored domain for this family of ligands. Notably, we observed a pronounced ability of this heterocyclic scaffold to establish π···π interactions in the solid state. The supramolecular π-stacked assemblies were theoretically analyzed using DFT calculations based on model structures.

Exploring the Remediation of Behavioral Disturbances of Spatial Cognition in Community-Dwelling Senior Citizens with Mild Cognitive Impairment via Innovative Technological Apparatus (BDSC-MCI Project): Protocol for a Prospective, Multi-Center Observational Study.

Spatial navigation (SN) has been reported to be one of the first cognitive domains to be affected in Alzheimer's disease (AD), which occurs as a result of progressive neuropathology involving specific brain areas. Moreover, the epsilon 4 isoform of apolipoprotein-E (APOE-ε4) has been associated with both sporadic and familial late-onset AD, and patients with mild cognitive impairment (MCI) due to AD are more likely to progressively deteriorate. Spatial navigation performance will be examined on a sample of 76 community-dwelling senior citizens (25 healthy controls; 25 individuals with subjective cognitive decline (SCD); and 26 patients with MCI due to AD) via a virtual computer-based task (i.e., the AppleGame) and a naturalistic task (i.e., the Detour Navigation Test-modified version) for which a wearable device with sensors will be used for recording gait data and revealing physiological parameters that may be associated with spatial disorientation. We expect that patients with MCI due to AD and APOE-ε4 carriers will show altered SN performances compared to individuals with SCD and healthy controls in the experimental tasks, and that VR testing may predict ecological performance. Impaired SN performances in people at increased risk of developing AD may inform future cognitive rehabilitation protocols for counteracting spatial disorientation that may occur during elders' traveling to unfamiliar locations. The research protocol has been approved by the Ethics Committee of the Istituto Auxologico Italiano. Findings will be published in peer-reviewed medical journals and discussed in national and international congresses.

The Telephone Language Screener (TLS): standardization of a novel telephone-based screening test for language impairment.

BACKGROUND: This study aimed at developing and standardizing the Telephone Language Screener (TLS), a novel, disease-nonspecific, telephone-based screening test for language disorders. METHODS: The TLS was developed in strict pursuance to the current psycholinguistic standards. It comprises nine tasks assessing phonological, lexical-semantic and morpho-syntactic components, as well as an extra Backward Digit Span task. The TLS was administered to 480 healthy participants (HPs), along with the Telephone-based Semantic Verbal Fluency (t-SVF) test and a Telephone-based Composite Language Index (TBCLI), as well as to 37 cerebrovascular/neurodegenerative patients-who also underwent the language subscale of the Telephone Interview for Cognitive Status (TICS-L). An HP subsample was also administered an in-person language battery. Construct validity, factorial structure, internal consistency, test-retest and inter-rater reliability were tested. Norms were derived via Equivalent Scores. The capability of the TLS to discriminate patients from HPs and to identify, among the patient cohort, those with a defective TICS-L, was also examined. RESULTS: The TLS was underpinned by a mono-component structure and converged with the t-SVF (p < .001), the TBCLI (p < .001) and the in-person language battery (p = .002). It was internally consistent (McDonald's ω = 0.67) and reliable between raters (ICC = 0.99) and at retest (ICC = 0.83). Age and education, but not sex, were predictors of TLS scores. The TLS optimally discriminated patients from HPs (AUC = 0.80) and successfully identified patients with an impaired TICS-L (AUC = 0.92). In patients, the TLS converged with TICS-L scores (p = 0.016). DISCUSSION: The TLS is a valid, reliable, normed and clinically feasible telephone-based screener for language impairment.

Verbal Learning Impairment in Parkinson's Disease: Role of the Frontostriatal System in Working and Strategic Memory.

INTRODUCTION: Learning is a long-term memory process, influenced by working memory control processes, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of the study was to investigate the verbal learning strategies of individuals with Parkinson's disease (PD). METHODS: Thirty individuals with idiopathic PD and healthy control (HC) subjects were tested with a multi-trial word list learning, under two conditions: without cue and then with an explicit cue suggesting the categories in the list, respectively. RESULTS: In comparison to HC subjects, individuals with PD recalled fewer words and achieved a reduced number of categorical clusters; the strategical cue did not improve their performance. CONCLUSION: This suggests, besides a difficulty in identifying the correct learning strategy, a deficit in working memory, which undermines the strategy implementation.

Does cognitive decline influence signing?

OBJECTIVE: The study explored the change in handwritten signature in neurodegenerative diseases by using of a rater-based approach. METHODS: Four independent observers were required to compare a pair of signatures (on average, 5 years elapsed between the two signatures) made by 103 patients (mean age 72 years) with Alzheimer's disease (AD) or frontotemporal dementia (FTD) and by 31 healthy participants (HC; mean age 73 years), judging their change according to a 0-1 rating scale (0 = similar or 1 = different). If a signature change was detected, the rater had also to report which signature features (spatial layout, omitted/added/switched letters or names, shape of letter, pen-flow) changed on the same 0-1 scale. For the AD and FTD groups, one signature was collected prior to the diagnosis of dementia, the other subsequent. RESULTS: A signature change was reported by raters in 36% of AD patients, 44% of FTD, and 17% of HC, with significant differences between both clinical groups and HC (vs. AD, p = .01; vs. FTD, p = .001). There was not a distinctive marker of the signature change (i.e., feature change) in patients with dementia. Moreover, the signature changes in neurological patients were unrelated to their clinical and demographic characteristics (age, sex, education, time elapsed between the two signatures, Mini-mental State Examination score). CONCLUSION: The findings suggest a resistance of handwritten signature in neurodegenerative diseases and in physiological aging, also suggesting that the signature may be an unreliable indicator of the cognitive status in AD and FTD, at least if subjectively evaluated.

Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer's Disease: Case Report and Review of the Literature.

We describe a case of amyotrophic lateral sclerosis (ALS) associated with Alzheimer's disease (AD) and review the literature about the coexistence of the two entities, highlighting the following: mean age at onset is 63.8 years, with slight female predominance; ALS tends to manifest after cognitive impairment and often begins in the bulbar region; average disease duration is 3 years; cognitive phenotype is mostly amnestic; the pattern of brain involvement is, in most cases, consistent with AD. Our case and the reviewed ones suggest that patients with ALS and dementia lacking unequivocal features of FTD should undergo additional examinations in order to recognize AD.

Two Cases of Malingered Crime-Related Amnesia.

Amnesia is a frequent claim in major crimes, and it is estimated that the complete or partial absence of memory following a crime ranges from 25% to 50% of total cases. Although some cases may constitute a genuine form of amnesia, due to organic-neurological defects or psychological causes, and possibly combined with a dissociative or repressive coping style after an extreme experience, malingering is still fairly common in offenders. Therefore, one of the main goals in medico-legal proceedings is to find methods to determine the credibility of crime-related amnesia. At present, a number of lie and memory detection techniques can assist the forensic assessment of the reliability of declarative proof, and have been devised and improved over the past century: for example, modern polygraphs, event-related potentials, thermal imaging, functional magnetic resonance imaging, kinematic, and facial analysis. Other ad hoc psychological tests, such as the so-called Symptom Validity Test (SVT) and Performance Validity Test (PVT), as well as the autobiographical Implicit Association Test (aIAT), can also be used. To date, however, there is little evidence or case reports that document their real usefulness in forensic practice. Here, we report two cases of crime-related amnesia, whereby both defendants, who were found guilty of homicide, appeared to exhibit dissociative amnesia but where the application of SVTs, PVTs, and aIAT detected a malingered amnesia.

Cognitive and behavioral involvement in ALS has been known for more than a century.

BACKGROUND: Among clinicians and researchers, it is common knowledge that, in ALS, cognitive and behavioral involvement within the spectrum of frontotemporal degenerations (FTDs) begun to be regarded as a fact in the late 1990s of the twentieth century. By contrast, a considerable body of evidence on cognitive/behavioral changes in ALS can be traced in the literature dating from the late nineteenth century. METHODS: Worldwide reports on cognitive/behavioral involvement in ALS dating from 1886 to 1981 were retrieved thanks to Biblioteca di Area Medica "Adolfo Ferrate," Sistema Bibliotecario di Ateneo, University of Pavia, Pavia, Italy and qualitatively synthetized. RESULTS: One-hundred and seventy-four cases of ALS with co-occurring FTD-like cognitive/behavioral changes, described in Europe, America, and Asia, were detected. Neuropsychological phenotypes were consistent with the revised Strong et al.'s consensus criteria. Clinical observations were not infrequently supported by histopathological, post-mortem verifications of extra-motor, cortical/sub-cortical alterations, as well as by in vivo instrumental exams-i.e., assessments of brain morphology/physiology and psychometric testing. In this regard, as earlier as 1907, the notion of motor and cognitive/behavioral features in ALS yielding from the same underlying pathology was acknowledged. Hereditary occurrences of ALS with cognitive/behavioral dysfunctions were reported, as well as familial associations with ALS-unrelated brain disorders. Neuropsychological symptoms often occurred before motor ones. Bulbar involvement was at times acknowledged as a risk factor for cognitive/behavioral changes in ALS. DISCUSSION: Historical observations herewith delivered can be regarded as the antecedents of current knowledge on cognitive/behavioral impairment in the ALS-FTD spectrum.

The Italian telephone-based Verbal Fluency Battery (t-VFB): standardization and preliminary clinical usability evidence.

Background: This study aimed at standardizing and providing preliminary evidence on the clinical usability of the Italian telephone-based Verbal Fluency Battery (t-VFB), which includes phonemic (t-PVF), semantic (t-SVF) and alternate (t-AVF) verbal fluency tasks. Methods: Three-hundred and thirty-five Italian healthy participants (HPs; 140 males; age range = 18-96 years; education range = 4-23 years) and 27 individuals with neurodegenerative or cerebrovascular diseases were administered the t-VFB. Switch number and cluster size were computed via latent semantic analyses. HPs underwent the telephone-based Mental State Examination (MMSE) and Backward Digit Span (BDS). Construct validity, factorial structure, internal consistency, test-retest and inter-rater reliability and equivalence with the in-person Verbal Fluency tasks were assessed. Norms were derived via Equivalent Scores. Diagnostic accuracy against clinical populations was assessed. Results: The majority of t-VFB scores correlated among each other and with the BDS, but not with the MMSE. Switch number correlated with t-PVF, t-SVF, t-AVF scores, whilst cluster size with the t-SVF and t-AVF scores only. The t-VFB was underpinned by a mono-component structure and was internally consistent (Cronbach's α = 0.91). Test-retest (ICC = 0.69-0.95) and inter-rater reliability (ICC = 0.98-1) were optimal. Each t-VFB test was statistically equivalent to its in-person version (equivalence bounds yielding a p < 0.05). Education predicted all t-VFB scores, whereas age t-SVF and t-AVF scores and sex only some t-SVF scores. Diagnostic accuracy against clinical samples was optimal (AUC = 0.81-0.86). Discussion: The t-VFB is a valid, reliable and normed telephone-based assessment tool for language and executive functioning, equivalent to the in-person version; results show promising evidence of its diagnostic accuracy in neurological populations.

Telephone-based Frontal Assessment Battery (t-FAB): standardization for the Italian population and clinical usability in neurological diseases.

BACKGROUND: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB). METHODS: The t-FAB (ranging 0-12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18-96 years; education range = 4-23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test-retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores. RESULTS: In HPs, t-FAB measures yielded high inter-rater/test-retest reliability (ICC = .78-.94), were internally related (p ≤ .005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤ .0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds < .001). Education predicted all t-FAB scores (p < .001), whereas age only the t-FAB-M score (p ≤ .004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (rs = .43-.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC = .73-.76). DISCUSSION: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice.