The Italian version of Cognitive Function Instrument (CFI) for tracking changes in healthy elderly: results at 1-year follow-up.

Cognitive Function Instrument (CFI) is a questionnaire aimed at detecting very early changes in cognitive and functional abilities and useful for monitoring cognitive decline in individuals without clinical impairment. The Italian version has been recently validated. The aim of the present study was to investigate the utility of the Italian version of CFI in tracking early cognitive changes in a cohort of healthy elderly subjects. A consecutive series of 257 cognitively healthy and functionally independent subjects, recruited either among relatives of patients attending our Memory Clinic or as volunteers after advertisement, underwent a baseline neuropsychological assessment. Of them, 157 subjects performed a 1-year follow-up assessment. All subjects completed the CFI, a short questionnaire composed of 14 items administered to both the subject and the referent (study-partner). Cognitive performance was assessed by Mini-Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). At 1-year follow-up, Cronbach's α was 0.79 (95% CI, 0.74-0.84) in self-report and 0.83 (95% CI, 0.79-0.87) for partner-report. CFI self-report correlated with MMSE (rS = - 0.22, p = 0.006) and RBANS (rS = - 0.23, p = 0.004). CFI partner-report showed negative correlation with MMSE (rS = - 0.17, p = 0.037) and RBANS (rS = - 0.20, p = 0.014). CFI 1-year follow-up score correlated with baseline both in self-report (rS = 0.56, p < 0.001) and partner-report (rS = 0.66, p < 0.001). Baseline CFI partner-report (p = 0.014) and CFI self+partner report (p = 0.023) were associated with RBANS total score less than 85 at 1-year follow-up, while only a trend was found considering baseline CFI self-report. Our results support the suitability of the Italian version of CFI for tracking cognitive changes along aging.

The Italian version of cognitive function instrument (CFI): reliability and validity in a cohort of healthy elderly.

The Alzheimer's disease Cooperative Study (ADCS)-Cognitive Function Instrument (CFI) is a 14-item questionnaire administered to the subject and the referent, aimed at detecting early changes in cognitive and functional abilities in individuals without clinical impairment. It is used for monitoring annual variations in cognitive functioning in prevention trials. The aim of the present study was to validate the Italian version of the CFI. A consecutive series of 257 functionally independent subjects was recruited among relatives of patients or as volunteers. They were administered CFI and global cognition measurements: Mini-Mental Status Examination (MMSE) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The reliability and criterion validity were comparable to the original in both self- and partner-report. Similarly to what reported in the original version, we found a corrected item-total correlation ranging between 0.38 and 0.54 in self-report and between 0.33 and 0.64 in partner-report. Cronbach's α was 0.77 (95% CI 0.72-0.83) in self-report and 0.78 (95% CI 0.73-0.84) in partner-report. Total partner- and self-report scores were significantly correlated (rS = 0.31, p < 0.001). CFI self-report and CFI total-score (partner + self-report) were negatively correlated with MMSE (rS = - 0.15, p = 0.022; rS = - 0.17, p = 0.008) and RBANS (rS = - 0.22, p < 0.001; rS = - 0.25, p < 0.001). Analogous trends were found in the partner score, with a correlation with RBANS (rS = - 0.17, p = 0.014) and MMSE (rS = - 0.11, p = 0.071). Our results support the reliability and validity of the Italian version of CFI. In order to definitely propose the use of CFI for tracking longitudinal changes of cognitive and functional abilities in subjects without clinical impairment, data from the follow-up of this cohort are needed.

Predictive value for cerebrospinal fluid Alzheimer's disease profile of different measures of verbal episodic memory in patients with MCI.

Neuropsychological evidence of memory impairment represents the main feature of the clinical onset of typical Alzheimer's disease (AD). Rey's Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) are two tests both assessing verbal episodic memory, widely used in clinical practice. Our aim was to investigate the added value of their combined use in predicting cerebrospinal fluid (CSF) AD biomarkers positivity in a retrospective consecutive series of patients with mild cognitive impairment (MCI). 169 MCI patients were included. For all of them neuropsychological assessment and CSF analysis were available. According to CSF A/T/(N) profile, 109 were defined as MCI due to AD (A+T+), and 60 were non-AD MCI (A-T-). Logistic regression model and receiver-operating characteristic (ROC) curves were analyzed to evaluate the discriminatory power of single and combined sub-measures between AD and non-AD patients. The combination of RAVLT-del with LM could acceptably discriminate the two groups (AUC: 0.69, CI 95% 0.617-0.761, sens: 0.75, spec. 0.58, p < 0.001), while the single tests did not show sufficient discriminative performance. Our study shows that the combination of RAVLT delayed recall with LM better predicts the biological AD diagnosis (A+T+), showing a good discriminative power between MCI-AD from non-AD MCI. Since RAVLT and LM assess different components of verbal episodic memory, they should be considered as complementary, rather than interchangeable, tests.

Repeatable Battery for the Assessment of Neuropsychological Status: Italian Normative Data for Older Adults.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), widely used for detecting cognitive impairment in different neuropsychiatric conditions, is increasingly applied for measuring cognitive functioning in older individuals. Available normative data for RBANS Italian version suffer from under-representation of the older ages (>60 years) and are not corrected for education. Moreover, normative data are provided only for Indexes and Total scores. We thus administered RBANS Italian version in a larger sample of older adults, taking into account the effect of age, education and gender on all scores. METHOD: We used a regression-based model to assess the effect of age, education, and gender on RBANS Subtests, Indexes and Total scores in a consecutive series of healthy cognitively normal volunteers aged 60-79 years (N = 158). The obtained norms were compared with the Italian original normative data by means of Wilcoxon rank-sum test. RESULTS: Multiple linear regression analyses showed that age and educational level significantly influence performances on most RBANS scores. A free-to-use Excel to calculate subject's percentiles for any single score was developed. When compared with original normative values, our percentiles distribution of Indexes and Total scores did not reveal significant differences (p > .05). CONCLUSION: The obtained normative data show good concordance with previous norms. The instrument seems not significantly affected by educational level. The possibility to correct for any single score could make RBANS a more precise measure for capturing subtle cognitive deficits in prevention studies.

CSF neurochemical profile and cognitive changes in Parkinson's disease with mild cognitive impairment.

Pathophysiological substrate(s) and progression of Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) are still matter of debate. Baseline cerebrospinal fluid (CSF) neurochemical profile and cognitive changes after 2 years were investigated in a retrospective series of PD-MCI (n = 48), cognitively normal PD (PD-CN, n = 40), prodromal Alzheimer's disease (MCI-AD, n = 25) and cognitively healthy individuals with other neurological diseases (OND, n = 44). CSF biomarkers reflecting amyloidosis (Aß42/40 ratio, sAPPα, sAPPß), tauopathy (p-tau), neurodegeneration (t-tau, NfL, p-NfH), synaptic damage (α-syn, neurogranin) and glial activation (sTREM2, YKL-40) were measured. The great majority (88%) of PD-MCI patients was A-/T-/N-. Among all biomarkers considered, only NfL/p-NfH ratio was significantly higher in PD-MCI vs. PD-CN (p = 0.02). After 2 years, one-third of PD-MCI patients worsened; such worsening was associated with higher baseline levels of NfL, p-tau, and sTREM2. PD-MCI is a heterogeneous entity requiring further investigations on larger, longitudinal cohorts with neuropathological verification.

Educational interventions to improve detection and management of cognitive decline in primary care-An Italian multicenter pragmatic study.

Introduction: Timely detection of cognitive decline in primary care is essential to promote an appropriate care pathway and enhance the benefits of interventions. We present the results of a study aimed to evaluate the effectiveness of an educational intervention addressed to Italian family physicians (FPs) to improve timely detection and management of cognitive decline. Materials and methods: We conducted a pre-post study in six Italian health authorities (HAs) involving 254 FPs and 3,736 patients. We measured process and outcome indicators before the intervention (1 January 2014 to 31 December 2016) and after the intervention (1 January 2018 to 31 December 2019). One interactive face-to-face session workshop was delivered by local cognitive disorders and dementia specialists and FP advisors at each HA, in the period September 2017-December 2017. The session focused on key messages of the local Diagnostic and Therapeutic Care Pathway (DTCP) or regional guidelines: (a) the role of the FP for a timely suspicion of cognitive decline is fundamental; (b) when cognitive decline is suspected, the role of the FP is active in the diagnostic work-up; (c) FP's knowledge on pharmacological and non-pharmacological interventions is essential to improve the management of patients with cognitive decline. Results: An overall improvement in diagnostic procedures and management of patients with cognitive decline by FPs after the intervention was observed. The number of visits per year performed by FPs increased, and the time interval between the first FP consultation and the diagnosis was optimized. Neuroleptic use significantly decreased, whereas the use of benzodiazepines remained steadily high. Non-pharmacological interventions, or use of support services, were underrepresented even in the post-intervention. Differences among the participating HAs were identified and discussed. Discussion: Results from this study suggest the success of the educational intervention addressed to FPs in improving early detection and management of cognitive decline, highlighting the importance to continue medical education in this field. At the same time, further initiatives of care pathway dissemination and implementation should promote strategies to enhance interactions between primary and secondary care optimizing the collaboration between FPs and specialists.

Automatic multispectral MRI segmentation of human hippocampal subfields: an evaluation of multicentric test-retest reproducibility.

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test-retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal ("long_T1s" and "long_T1s_FLAIR") and one cross-sectional ("long_T1s_FLAIR_crossT2"). Volume reproducibility was quantified in magnitude (reproducibility error-RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4-3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1-7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm3 had better RE (1-2%) and DICE (0.7-0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements.