Heterogeneity and overlap in the continuum of linguistic profile of logopenic and semantic variants of primary progressive aphasia: a Profile Analysis based on Multidimensional Scaling study.

BACKGROUND: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce. METHODS: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [18F] FDG-PET. Correlations were performed between metabolic and behavioral data. RESULTS: Patients' profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space. DISCUSSION: Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups.

Diagnostic Performance of Socio-Emotional Informant-Based Questionnaires for the Clinical Detection of the Behavioral Variant of Frontotemporal Dementia.

BACKGROUND: Although social cognitive dysfunction is a major feature of the behavioral variant of frontotemporal dementia (bvFTD), quantitative measurement of social behavior changes is poorly available in clinical settings. OBJECTIVE: The aim of the study is to evaluate diagnostic accuracy of social-emotional questionnaires in distinguishing bvFTD from healthy control (HC) subjects and Alzheimer's disease (AD) patients. METHODS: We enrolled 29 bvFTD, 24 AD, and 18 HC subjects matched for age, sex, and education. Two informant-based measures of socio-emotional sensitivity and empathy (i.e., revised Self-Monitoring Scale (rSMS) and Interpersonal Reactivity Index (IRI)) were administered. One-way ANOVA was performed to compare groups, whereas Receiver Operating Characteristics (ROC) curve analysis tested questionnaire ability in distinguishing groups. A short version of IRI (sIRI) was obtained by excluding the non-contributing subscale (i.e., personal distress). RESULTS: Compared to HC and AD, bvFTD showed significantly lower scores in rSMS and IRI scores, except for IRI personal distress subscale. The sIRI showed an excellent performance in early diagnosis (bvFTD versus HC = AUC 0.95). Both sIRI and rSMS showed good performance in distinguishing bvFTD from AD (AUC 0.83). CONCLUSIONS: ROC analyses support the usefulness of informant social questionnaires in memory clinics and their potential value in screening procedures for research eligibility in forthcoming trials. In the timely diagnosis of bvFTD patients, IRI and rSMS may supply crucial information for the early detection of signs and symptoms affecting social-emotional skills, which might otherwise be underrecognized.

Effects of an educational planetary plate graphic on meat consumption in a Stanford University dining hall: a randomized controlled trial.

BACKGROUND: Assess the impact of an educational Planetary Health Plate (PHP) graphic on meat-related dietary choices of Stanford University dining hall patrons using a randomized controlled trial crossover design. All patrons entering the dining hall during study periods were enrolled as participants. Control, n = 631; PHP, n = 547. METHODS: Compare dietary behavior without signage to behavior while exposed to PHP during four equivalent dinner meals. The primary outcome was total meat-dish weight adjusted for the number of people entering the dining hall. Secondary outcomes included the number of meat-dish servings and average meat-dish serving weight. Analysis using T-tests, Poisson generalized linear model. RESULTS: Differences in total meat-dish weight, (1.54 kg; 95% Confidence Interval [CI] = -4.41,1.33; P = .19) and average meat-dish serving weight (0.03 kg; 95% CI = 0.00, 0.06; P = .07) between PHP and control patrons did not reach significance. The rate at which PHP patrons took meat was significantly lower (Incidence Rate Ratio 0.80; 95% CI = 0.71, 0.91; P < .001). CONCLUSION: Exposure to an educational plate graphic decreased the proportion of patrons taking meat but had no impact on total meat consumption or meat-dish serving weight. Statistical methods used in this study may inform future investigations on dietary change in the dining hall setting. Further research on the role of educational signage in influencing dietary behavior is warranted, with an aim to improve human health and environmental sustainability. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05565859, registered 4 October 2022.

Comparing two picture naming tasks in primary progressive aphasia: Insights from behavioural and neural results.

Picture naming tests are widely used to evaluate language impairments in neurodegenerative diseases, especially in Primary Progressive Aphasia (PPA). The available tests differ for many factors affecting the performance, e.g. format of stimuli and their psycholinguistic properties. We aim to identify the most appropriate naming test to be used on PPA according to the clinical and research demands. We investigated the behavioural characteristics, i.e. proportion of correct responses and error type, and their neural correlates in two Italian naming tests, CaGi naming (CaGi) and naming subtest of the Screening for Aphasia in NeuroDegeneration battery (SAND), administered to 52 PPA patients who underwent an FDG-PET scan. We analysed the effectiveness of the tests in distinguishing PPA versus controls and among PPA variants, considering the psycholinguistic variables affecting performance. We explored the brain metabolic correlates of behavioural performance in the tests. SAND, differently from CaGi, has time limits for the response and its items are less frequent and acquired later. SAND and CaGi differed in terms of number of correct responses and error profile, suggesting a higher difficulty to name SAND items compared to CaGi. Semantic errors predominated in CaGi, while anomic and semantic errors were equally frequent in SAND. Both tests distinguished PPA from controls, but SAND outperformed CaGi in discriminating among PPA variants. FDG-PET imaging revealed a shared metabolic involvement of temporal areas associated with lexico-semantic processing, encompassing anterior fusiform, temporal pole, and extending to posterior fusiform in sv-PPA. Concluding, a picture naming test with response time limit and items which are less frequent and acquired later in life, as SAND, may be effective at highlighting subtle distinctions between PPA variants, improving the diagnosis. Conversely, a naming test without time limit for the response, as CaGi, may be useful for a better characterization of the nature of the naming impairment at the behavioural level, eliciting more naming errors than anomia, possibly helping in the development of rehabilitation protocols.

Comprehensive qualitative characterization of linguistic performance profiles in primary progressive aphasia: a multivariate study with FDG-PET.

Primary progressive aphasia (PPA) classification relies on profile characterization of quantitatively impaired/spared performance in language tasks. In this study, we coextracted 8 qualitative types of errors in 67 PPA patients submitted to a comprehensive language assessment. Canonical correlation analysis was applied to simultaneously correlate qualitative errors and brain metabolism, collected with FDG-PET. Results showed the contribution of semantic, syntactic and working memory errors associated with specific correlates of regional metabolic changes. Reduced metabolism in the left fusiform gyrus, anterior-middle and inferior-temporal gyri and middle-temporal pole correlated with an increase of semantic errors. Hypometabolism in the left inferior, middle, and superior frontal gyri, insula and right middle-occipital gyrus was related to syntactic errors. Higher metabolism in the bilateral pallidum, putamen, and left thalamus, as well as hypometabolism in the left angular and supramarginal gyri, inferior-parietal lobule, posterior-middle and inferior-temporal gyri and posterior cingulum predicted the increase of working memory errors. A relevant role of working memory subcomponents was associated with distinct neural systems. Patients' profiles are easily represented in a qualitative multidimensional space, in which mixed PPA overlapped with different phenotypes.

Early Identification of Different Behavioral Phenotypes in the Behavioral Variant of Frontotemporal Dementia with the Aid of the Mini-Frontal Behavioral Inventory (mini-FBI).

BACKGROUND: The Frontal Behavioral Inventory (FBI) is a questionnaire designed to quantify behavioral changes in frontotemporal dementia (FTD). Literature showed heterogeneous FBI profiles in FTD versus Alzheimer's disease (AD) with variable occurrence of positive and negative symptoms. OBJECTIVE: In this study, we constructed a short FBI version (i.e., mini-FBI) with the aim to provide clinicians with a brief tool for the identification of early behavioral changes in behavioral variant of FTD (bvFTD), also facilitating the differential diagnosis with AD. METHODS: 40 bvFTD and 33 AD patients were enrolled. FBI items were selected based on internal consistency and exploratory factor analysis. Convergent validity of mini-FBI was also assessed. A behavioral index (i.e., B-index) representing the balance between positive and negative mini-FBI symptoms was computed in order to analyze its distribution in bvFTD through a cluster analysis and to compare performance among patient groups. RESULTS: The final version of the mini-FBI included 12 items, showing a significant convergent validity with the Neuropsychiatric Inventory scores (rp = 0.61, p < 0.001). Cluster analysis split patients in four clusters. bvFTD were included in three different clusters characterized by prevalent positive symptoms, both positive and negative symptoms, or prevalent negative behavioral alterations, similar to a subset of AD patients. A fourth cluster included only AD patients showing no positive symptoms. CONCLUSION: The mini-FBI is a valuable easily administrable questionnaire able to early identify symptoms effectively contributing to the bvFTD behavioral syndrome, aiding clinician in diagnosis and management.

Emotion Recognition Deficits in the Differential Diagnosis of Amnestic Mild Cognitive Impairment: A Cognitive Marker for the Limbic-Predominant Phenotype.

OBJECTIVE: Late-onset amnestic mild cognitive impairment (aMCI) with long disease course and slow progression has been recently recognized as a possible phenotypical expression of a limbic-predominant neurodegenerative disorder. Basic emotion recognition ability crucially depending on temporo-limbic integrity is supposed to be impaired in this group of MCI subjects presenting a selective vulnerability of medio-temporal and limbic regions. However, no study specifically investigated this issue. METHODS: Hereby, we enrolled 30 aMCI with a biomarker-based diagnosis of Alzheimer's disease (i.e., aMCI-AD, n = 16) or a biomarker evidence of selective medio-temporal and limbic degeneration (aMCI-mTLD, n = 14). Ekman-60 Faces Test (Ek-60F) was administered to each subject, comparing the performance with that of 20 healthy controls (HCs). RESULTS: aMCI-mTLD subjects showed significantly lower Ek-60F global scores compared to HC (p = 0.001), whose performance was comparable to aMCI-AD. Fear (p = 0.02), surprise (p = 0.005), and anger (p = 0.01) recognition deficits characterized the aMCI-mTLD performance. Fear recognition scores were significantly lower in aMCI-mTLD compared to aMCI-AD (p = 0.04), while no differences were found in other emotions. CONCLUSIONS: Impaired social cognition, suggested by defective performance in emotion recognition tasks, may be a useful cognitive marker to detect limbic-predominant aMCI subjects among the heterogeneous aMCI population.

Changes in Ultra-Processed Food Consumption and Lifestyle Behaviors Following COVID-19 Shelter-in-Place: A Retrospective Study.

Ultra-processed food (UPF) consumption poses a potential risk to public health and may be related to shelter-in-place orders. This study utilized the level of food processing as a lens by which to examine the relationships between diet, weight change, and lifestyle changes (including cooking, snacking, and sedentary activity) that occurred during regional shelter-in-place orders. This study used a cross-sectional, retrospective survey (n = 589) to assess baseline demographics, changes in lifestyle behaviors using a Likert scale, and changes in dietary behaviors using a modified food frequency questionnaire from mid-March to May 2020; data were collected in the California Bay Area from August to October 2020. Foods were categorized by level of processing (minimally processed, processed, and ultra-processed) using the NOVA scale. Stepwise multiple linear regression and univariate linear regression models were used to determine the associations between these factors. Increased snacking was positively associated with a change in the percent of the calories derived from UPF and weight gain (ß = 1.0, p < 0.001; ß = 0.8 kg, p < 0.001) and negatively associated with the share of MPF calories consumed (ß = -0.9, p < 0.001). These relationships have public health implications as interventions designed around decreased snacking may positively impact diet and weight management and thereby mitigate negative health outcomes.

Diagnostic Accuracy of Affective Social Tasks in the Clinical Classification Between the Behavioral Variant of Frontotemporal Dementia and Other Neurodegenerative Disease.

BACKGROUND: Severe socio-emotional impairments characterize the behavioral variant of frontotemporal dementia (bvFTD). However, literature reports social cognition disorders in other dementias. OBJECTIVE: In this study, we investigated the accuracy of social cognition performances in the early and differential diagnosis of bvFTD. METHODS: We included 131 subjects: 32 bvFTD, 26 Alzheimer's disease (AD), 16 primary progressive aphasia (PPA), 17 corticobasal syndrome (CBS), and 40 healthy control (HC). Each subject completed the Ekman 60 faces (Ek-60F) test assessing basic emotion recognition and the Story-based Empathy Task (SET) assessing attribution of intentions/emotions. A combined social measure (i.e., Emotion Recognition and Attribution (ERA) index) was calculated. One-way ANOVA has been used to compare performances among groups, while receiver operating characteristic (ROC) curve tested measures ability to distinguish subjects with and without bvFTD. RESULTS: Ek-60F and ERA index scores were significantly lower in bvFTD versus HC, AD, and PPA groups. ROC analyses significantly distinguished bvFTD from HC (AUC 0.82-0.92), with the Ek-60F test showing the highest performance, followed by the ERA index. These two social measures showed the best accuracy in detecting bvFTD from AD (AUC 0.78-0.74) and PPA (AUC 0.80-0.76). Investigated measures failed in detecting bvFTD from CBS. CONCLUSION: Accuracy analyses support the advantage of using social cognition tests for bvFTD diagnosis. Short social battery may reduce uncertainties and improve disease identification in clinical settings. We recommend a revision of current clinical criteria considering neuropsychological deficits in emotion recognition and processing tasks as key cognitive markers of this neurodegenerative syndrome.

Individual Brain Metabolic Signatures in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is the usual clinical presentation of patients with corticobasal degeneration pathology. Nevertheless, there are CBS individuals with postmortem neuropathology typical of Alzheimer's disease (AD). OBJECTIVE: In this study, we aim to detect FDG-PET metabolic signatures at the single-subject level in a CBS sample, also evaluated with cerebrospinal fluid (CSF) markers for AD pathology. METHODS: 21 patients (68.9±6.4 years; MMSE score = 21.7±6.3) fulfilling current criteria for CBS were enrolled. All underwent a clinical-neuropsychological assessment and an instrumental evaluation for biomarkers of neurodegeneration, amyloid and tau pathology (i.e., FDG-PET imaging and CSF Aß42 and tau levels) at close intervals. CBS subjects were classified according to the presence or absence of CSF markers of AD pathology (i.e., low Aß42 and high phosphorylated tau levels). Optimized voxel-based SPM procedures provided FDG-PET metabolic patterns at the single-subject and group levels. RESULTS: Eight CBS had an AD-like CSF profile (CBS-AD), while thirteen were negative (CBS-noAD). The two subgroups did not differ in demographic characteristics or global cognitive impairment. FDG-PET SPM t-maps identified different metabolic signatures. Namely, all CBS-AD patients showed the typical AD-like hypometabolic pattern involving posterior cingulate cortex, precuneus and temporo-parietal cortex, whereas CBS-noAD cases showed bilateral hypometabolism in fronto-insular cortex and basal ganglia that is typical of the frontotemporal lobar degeneration spectrum. DISCUSSION: These results strongly suggest the inclusion of FDG-PET imaging in the diagnostic algorithm of individuals with CBS clinical phenotype in order to early identify functional metabolic signatures due to different neuropathological substrates, thus improving the diagnostic accuracy.

Diffusion tensor imaging evidence of corticospinal pathway involvement in frontotemporal lobar degeneration.

Motor neuron dysfunctions (MNDys) in Frontotemporal Lobar Degeneration (FTLD) have been consistently reported. Clinical and neurophysiological findings proved a variable range of pathological changes, also affecting the corticospinal tract (CST). This study aims to assess white-matter microstructural alterations in a sample of patients with FTLD, and to evaluate the relationship with MNDys. Fifty-four FTLD patients (21 bvFTD, 16 PPA, 17 CBS) and 36 healthy controls participated in a Diffusion Tensor Imaging (DTI) study. We analyzed distinctive and common microstructural alteration patterns across FTLD subtypes, including those affecting the CST, and performed an association analysis between CST integrity and the presence of clinical and/or neurophysiological signs of MNDys. The majority of FTLD patients showed microstructural changes in the motor pathway with a high prevalence of CST alterations also in patients not displaying clinical and/or neurophysiological signs of MNDys. Our results suggest that subtle CST alterations characterize FTLD patients regardless to the subtype. This may be due to the spread of the pathological process to the motor system, even without a clear clinical manifestation of MNDys.

Randomized controlled trial on the efficacy of a multilevel non-pharmacologic intervention in older adults with subjective memory decline: design and baseline findings of the E.Mu.N.I. study.

BACKGROUND: Alzheimer's Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults. OBJECTIVES: The E.Mu.N.I study is a randomized controlled trial investigating the effect of multilevel non-pharmacologic interventions on cognitive performances (primary outcome) and structural and vascular brain MRI markers (secondary outcome), as well as markers of brain functional connectivity change (exploratory outcome), in older adults with subjective memory decline (SMD). Here, we present the study design and the baseline features of the sample. METHODS: Cognitively intact older adults with SMD, enrolled between February 2016 and June 2017, were randomly assigned to one of the 3 interventions for 1 year: Active Control Intervention (ACI), i.e., educational lessons; Partial Intervention (PI), i.e., homotaurine administration (100 mg/die) and lessons on the Mediterranean diet; Multilevel Intervention (MI), i.e., PI plus computerized cognitive training and physical exercise training. RESULTS: One-hundred and twenty-eight eligible participants were enrolled (66% female; age: 68 ± 5 years). Eighty-two percent of the sample was composed of volunteers with SMD from the community. Participants were randomly allocated to the interventions as follows: ACI (N = 40), PI (N = 44), MI (N = 44). No significant differences among groups emerged on socio-demographic, clinical-neuropsychological variables and MRI markers at baseline. CONCLUSIONS: The outcomes obtained from the E.Mu.N.I. study will clarify the efficacy of multilevel non-pharmacologic interventions on cognitive and neuroimaging markers in SMD individuals. This is a crucial step forward for the development of cost-effective non-pharmacologic primary prevention initiatives for AD.

The clinico-metabolic correlates of language impairment in corticobasal syndrome and progressive supranuclear palsy.

PURPOSE: To assess the clinical-metabolic correlates of language impairment in a large sample of patients clinically diagnosed as corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPs). METHODS: We included 70 patients fulfilling current criteria for CBS (n = 33) or PSPs (n = 37). All subjects underwent clinical-neuropsychological and FDG-PET assessments at the time of diagnosis. The whole patient's cohort was grouped into three subgroups according to the language characteristics, i.e., (a) nfv-PPA; (b) subtle language impairments, LANG-; (c) no language deficits, NOL-. FDG-PET data were analysed using an optimized voxel-based SPM method at the single-subject and group levels in order to evaluate specific hypometabolic patterns and regional dysfunctional FDG-PET commonalities in subgroups. RESULTS: 21 patients had a nfvPPA diagnosis (i.e., nfv-PPA/CBS = 12 and nfv-PPA/PSPs = 9), while 20 patients had a subtle language impairment LANG- (i.e., CBS = 12 and PSPs = 8), not fulfilling the criteria for a nfv-PPA diagnosis. The remaining sample (i.e., 9/33 CBS and 20/37 PSPs patients) did not show any language deficit. FDG-PET results in individuals with a nfv-PPA diagnosis were consistent with the typical nfv-PPA pattern of hypometabolism (i.e., left fronto-insular and superior medial frontal cortex involvement), both in CBS and PSPs. The LANG-CBS and LANG-PSPs subjects had different FDG-PET hypometabolic patterns involving, respectively, parietal and frontal regions. As expected, NOL-CBS and NOL-PSPs showed a predominant right hemisphere involvement, with selective functional metabolic signatures typical of the two syndromes. CONCLUSIONS: Language impairments, fulfilling the nfv-PPA criteria, are associated with both CBS and PSPs clinical presentations early in the disease course. Subtle language deficits may be present in an additional proportion of patients not fulfilling the nfv-PPA criteria. The topography of brain hypometabolism is a major dysfunctional signature of language deficits in CBS and PSPs clinical phenotypes.

Variant-specific vulnerability in metabolic connectivity and resting-state networks in behavioural variant of frontotemporal dementia.

Brain connectivity measures represent candidate biomarkers of neuronal dysfunction in neurodegenerative diseases. Previous findings suggest that the behavioural variant of frontotemporal dementia (bvFTD) and its variants (i.e., frontal and temporo-limbic) may be related to the vulnerability of distinct functional connectivity networks. In this study, 82 bvFTD patients were included, and two patient groups were identified as frontal and temporo-limbic bvFTD variants. Two advanced multivariate analytical approaches were applied to FDG-PET data, i.e., sparse inverse covariance estimation (SICE) method and seed-based interregional correlation analysis (IRCA). These advanced methods allowed the assessment of (i) the whole-brain metabolic connectivity, without any a priori assumption, and (ii) the main brain resting-state networks of crucial relevance for cognitive and behavioural functions. In the whole bvFTD group, we found dysfunctional connectivity patterns in frontal and limbic regions and in all major brain resting-state networks as compared to healthy controls (HC N = 82). In the two bvFTD variants, SICE and IRCA analyses identified variant-specific reconfigurations of whole-brain connectivity and resting-state networks. Specifically, the frontal bvFTD variant was characterised by metabolic connectivity alterations in orbitofrontal regions and anterior resting-state networks, while the temporo-limbic bvFTD variant was characterised by connectivity alterations in the limbic and salience networks. These results highlight different neural vulnerabilities in the two bvFTD variants, as shown by the dysfunctional connectivity patterns, with relevance for the different neuropsychological profiles. This new evidence provides further insight in the variability of bvFTD and may contribute to a more accurate classification of these patients.

A biomarker study in long-lasting amnestic mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer's disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup. METHODS: Thirty consecutive subjects with aMCI who had long-lasting memory impairment (more than 4 years from symptom onset) and a very slow rate of cognitive progression were included. All subjects underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) metabolic imaging. A measure of cerebral amyloid load, by PET and/or CSF, was obtained in 26 of 30 subjects. The mean clinical follow-up was 58.3 ± 10.1 months. RESULTS: No patient progressed to dementia during the follow-up. The typical AD FDG-PET pattern of temporoparietal hypometabolism was not present in any of the subjects. In contrast, a selective medial temporal lobe hypometabolism was present in all subjects, with an extension to frontolimbic regions in some subjects. PET imaging showed absent or low amyloid load in the majority of samples. The values were well below those reported in prodromal AD, and they were slightly elevated in only two subjects, consistent with the CSF ß-amyloid (1-42) protein values. Notably, no amyloid load was present in the hippocampal structures. CONCLUSIONS: FDG-PET and amyloid-PET together with CSF findings questioned AD pathology as a unique neuropathological substrate in this aMCI subgroup with long-lasting disease course. The possibility of alternative pathological conditions, such as argyrophilic grain disease, primary age-related tauopathy or age-related TDP-43 proteinopathy, known to spread throughout the medial temporal lobe and limbic system structures should be considered in these patients with MCI.

Combined Socio-Behavioral Evaluation Improves the Differential Diagnosis Between the Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: In Search of Neuropsychological Markers.

BACKGROUND: Current diagnostic criteria for behavioral variant of frontotemporal dementia (bvFTD) and typical Alzheimer's disease (AD) include a differential pattern of neuropsychological impairments (episodic memory deficit in typical AD and dysexecutive syndrome in bvFTD). There is, however, large evidence of a frequent overlap in neuropsychological features, making the differential diagnosis extremely difficult. OBJECTIVES: In this retrospective study, we evaluated the diagnostic value of different cognitive and neurobehavioral markers in bvFTD and AD patient groups. METHODS: We included 95 dementia patients with a clinical and biomarker evidence of bvFTD (n = 48) or typical AD (n = 47) pathology. A clinical 2-year follow-up confirmed clinical classification. Performances at basic cognitive tasks (memory, executive functions, visuo-spatial, language) as well as social cognition skills and neurobehavioral profiles have been recorded. A stepwise logistic regression model compared the neuropsychological profiles between groups and assessed the accuracy of cognitive and neurobehavioral markers in discriminating bvFTD from AD. RESULTS: Statistical comparison between patient groups proved social cognition and episodic memory impairments as main cognitive signatures of bvFTD and AD neuropsychological profiles, respectively. Only half of bvFTD patients showed attentive/executive deficits, questioning their role as cognitive marker of bvFTD. Notably, the large majority of bvFTD sample (i.e., 70%) poorly performed at delayed recall tasks. Logistic regression analysis identified social cognition performances, Frontal Behavioral Inventory and Mini-Mental State Examination scores as the best combination in distinguishing bvFTD from AD. CONCLUSION: Social cognition tasks and socio-behavioral questionnaires are recommended in clinical settings to improve the accuracy of early diagnosis of bvFTD.

Executive dysfunction affects word list recall performance: Evidence from amyotrophic lateral sclerosis and other neurodegenerative diseases.

The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice to evaluate verbal episodic memory. While there is evidence that RAVLT performance can be influenced by executive dysfunction, the way executive disorders affect the serial position curve (SPC) has not been yet explored. To this aim, we analysed immediate and delayed recall performances of 13 non-demented amyotrophic lateral sclerosis (ALS) patients with a specific mild executive dysfunction (ALSci) and compared their performances to those of 48 healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to control for the impact of a severe dysexecutive syndrome and a genuine episodic memory deficit on the SPC, we enrolled 15 patients with a diagnosis of behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with probable Alzheimer's disease (AD). Results documented that, compared to cognitively normal subjects, ALSci patients had a selective mid-list impairment for immediate recall scores. The bvFTD group obtained low performances with a selectively increased forgetting rate for terminal items, whereas the AD group showed a disproportionately large memory loss on the primary and middle part of the SPC for immediate recall scores and were severely impaired in the delayed recall trial. These results suggested that subtle executive dysfunctions might influence the recall of mid-list items, possibly reflecting deficiency in control strategies at retrieval of word lists, whereas severer dysexecutive syndrome might also affect the recall of terminal items possibly due to attention deficit or retroactive interference.

Construct validity of the Free and Cued Selective Reminding Test in older adults with memory complaints.

INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is the memory test recommended by the International Working Group on Alzheimer's disease (AD) for the detection of amnestic syndrome of the medial temporal type in prodromal AD. Assessing the construct validity and internal consistency of the Italian version of the FCSRT is thus crucial. METHODS: The FCSRT was administered to 338 community-dwelling participants with memory complaints (57% females, age 74.5 ± 7.7 years), including 34 with AD, 203 with Mild Cognitive Impairment, and 101 with Subjective Memory Impairment. Internal Consistency was estimated using Cronbach's alpha coefficient. To assess convergent validity, five FCSRT scores (Immediate Free Recall, Immediate Total Recall, Delayed Free Recall, Delayed Total Recall, and Index of Sensitivity of Cueing) were correlated with three well-validated memory tests: Story Recall, Rey Auditory Verbal Learning test, and Rey Complex Figure (RCF) recall (partial correlation analysis). To assess divergent validity, a principal component analysis (an exploratory factor analysis) was performed including, in addition to the above-mentioned memory tasks, the following tests: Word Fluencies, RCF copy, Clock Drawing Test, Trail Making Test, Frontal Assessment Battery, Raven Coloured Progressive Matrices, and Stroop Colour-Word Test. RESULTS: Cronbach's alpha coefficients for immediate recalls (IFR and ITR) and delayed recalls (DFR and DTR) were, respectively, .84 and .81. All FCSRT scores were highly correlated with those of the three well-validated memory tests. The factor analysis showed that the FCSRT does not load on the factors saturated by non-memory tests. CONCLUSIONS: These findings indicate that the FCSRT has a good internal consistency and has an excellent construct validity as an episodic memory measure.

The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia.

BACKGROUND AND OBJECTIVE: Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings. MATERIAL AND METHODS: 55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4±12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel-based SPM method at the single-subject level. RESULTS: FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline. DISCUSSION: Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes.