An observational study in Active Aging Individuals Aged 65 and Over, Aging and Mild Cognitive Impairment (MCI), sponsored by Neuromed IRCCS. Not yet recruiting at 8 sites in Italy. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-11.
Sponsored by Neuromed IRCCS · Observational
The goal of this experimental multicentric intervention study is to validate, in Italian, the dynamic Neurocognitive Adaptation (dNA) Scale, which has already been validated in English, among a healthy elderly population (aged 65 and older) residing in Italy and patients with dementia or Alzheimer's Disease. dNA is a questionnaire designed to assess both current and past levels of engagement in physical, cognitive, creative, and social activities.
The study aims to recruit a total of 265 participants with mild cognitive impairment, subjective memory complaints, or dementia. These participants will be distributed among the 8 recruitment centers. Neuropsychological data, subjective measures, and MRI data will be collected and analyzed to address the following research questions: 1) Is there a positive correlation between scores on the dNA Scale and cognitive efficiency, as reflected in neuropsychological measures, such as episodic memory and executive functions? 2) Is there a correlation between dNA scores and improved functional connectivity within neural networks, such as the Default Network (DN)?
Participants recruited at the participating clinical centers will undergo:
This study aims to validate the instrument known as the dynamic Neurocognitive Adaptation Scale (dNA), derived from the identical scale previously validated in English on a sample of 815 subjects residing in the United States. All the clinical centers involved will recruit approximately 265 subjects, administer the aforementioned scale, and collect demographic and medical history information. This information will be necessary and sufficient for the first part (Stage #1) of the instrument's validation. Actually, according to the literature, the number of participants required to validate a scale with 20 items- which has already been validated in another language-is approximately 250 participants. Other studies suggest a minimum of 200 subjects to test cross-cultural consistency and reliability. The dNA scale, already validated in English, reports a KM O index greater than .80 (i.e., good), a specific index (Kaiser-Meyer-Olkin) for confirming the appropriateness of the sample. Specifically, for the CFA, this sample size calculation accounts for the need to detect a medium effect size, expressed in terms of Root Mean Square Error of Approximation (RMSEA), with an expected value of 0.05, a statistical power (1-β) of 0.80, and a significance level α of 0.05. Taking potential dropouts into account, approximately 265 subjects will be recruited to ensure the minimum sample size required for statistical power, and this number will be verified experimentally during the validation phase using the KMO index.
Each of the 8 participating centers, depending on their recruitment capacity, will enroll approximately at least 30 participants. The majority of the final sample (i.e., 265 participants) will consist of healthy older adults (HC), while a smaller percentage will include subjects with subjective memory complaints (SMC), mild cognitive impairment (MCI), or Alzheimer's disease (AD).
The first phase (Stage #1) will be followed by a second part (Stage #2) focused on exploring the correlation between the dNA score and neuropsychological variables (particularly those related to memory and executive functions), with the aim of investigating a measure of adaptation that is primarily cognitive in nature. This adaptation will provide a measure of cognitive efficiency, commonly referred to in the literature as cognitive reserve or resilience. In this phase, adherence to a Mediterranean-style diet (i.e., the Mediterranean diet, assessed via a specific questionnaire) will also be explored as a protective factor against general inflammatory processes and cognitive decline associated with Alzheimer's disease (AD).
During the third phase (Stage #3), a measure of neural adaptation will be explored, collecting data on neural efficiency. In the literature, this is a form of resilience or adaptation often described as neural reserve. This component will be explored using structural magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI).
Demographic information, medical history, dietary habits, and neuropsychological data collected by the participating centers will be compiled and managed at the Universities of Chieti and Foggia, under the coordination and responsibility of Professor Michela Balsamo (CH) and Professor Leonardo Carlucci (FG), respectively, both of whom have established expertise in statistics and psychometrics, particularly in the validation of instruments within the field of psychology. The two universities will carry out the data analysis phase aimed at validating the scale (Stage #1), also accounting for key demographic variables (age, sex, education level).
For the primary analyses, principal component analysis (PCA) and exploratory factor analysis (EFA) will be conducted to identify the underlying structure of the dNA instrument and determine the number of components, forming the basis for a subsequent confirmatory factor analysis (CFA) in the validation sample. Descriptive statistics will be used to characterize the study sample. Prior to EFA, sample adequacy (KMO) and variance homogeneity (Bartlett's test) will be assessed, while internal consistency will be evaluated using Cronbach's alpha and inter-item correlations. CFA will be performed using a structural equation modeling (SEM) approach with maximum likelihood estimation to test the hypothesized factor structure. Model fit indices will be calculated, including chi-square (p-value > 0.05), root mean square error of approximation (RMSEA; cutoff ≤ 0.06), normed fit index (NFI), comparative fit index (CFI; cutoff ≥ 0.90), Tucker-Lewis index (TLI; cut-off ≥ 0.95), and standardized root mean square residual (SRMR; cut-off ≤ 0.08). Finally, the coefficient of determination (R²) will be calculated to assess the proportion of variance explained between factors.
Subsequently, during the second phase (Stage #2), dNA scale scores will be analyzed in relation to the aforementioned dietary habits and neuropsychological variables, particularly memory and executive functions. Correlation analyses will be conducted across the scale domains (cognitive, physical, creative, and social) using distance correlations. The domains will also be examined across the seven time periods considered in the dNA scale (i.e., childhood, adolescence, young adulthood, adulthood, midlife, senior age, and old age) using repeated-measures ANOVA (RM-ANOVA) with Greenhouse-Geisser sphericity corrections. Within-subject effects of time, as well as interactions between time, gender, and education level, will be assessed. Planned contrasts will be conducted within domains for specific pairwise time comparisons and significant interactions, followed by post hoc comparisons using the Bonferroni-Holm correction. Additionally, correlations between the scale and adherence to a Mediterranean diet, as well as performance on cognitive tests assessing memory and executive functions, will be evaluated. Moderation analyses will test whether higher dNA scores may moderate negative effects on neuropsychological outcomes (i.e., lower scores in memory and executive functions) and neurophysiological measures (i.e., poor anticorrelation between the default mode network and task-positive networks such as DAN/FPCN).
All participating clinical centers will collect demographic, medical history, dietary habit, neuropsychological, and, where available, imaging data (MRI, fMRI). These data will be used in the third phase (Stage #3), which will be focused on identifying the neural correlates of adaptation (i.e., neural efficiency) during aging. Imaging data collected by the participating clinical centers will be transferred to the University of Padua, which will oversee data receipt and analysis under the coordination and responsibility of Dr. Marco Marino, whose research focuses on the neural substrates underlying neurocognitive adaptation during aging.
In this phase, both structural (e.g., volumetric and cortical thickness) and functional (e.g., resting-state fMRI) analyses will be performed. Regions of interest (ROIs) will be defined based on prior literature and mapped from standard (MNI) space to individual brain space. Spherical ROIs will be created, and their activity will be summarized using principal component analysis. Functional connectivity maps will be generated by correlating ROI time series with whole-brain activity and then normalized to MNI space for group-level analyses, with statistical significance corrected for multiple comparisons (FDR). Graph theory analysis will be applied to the functional network generated with AAL Atlas (Tzourio-Mazoyer et al., 2002) using the GRETNA software (Wang et al., 2015). Five global indices derived from the graph analysis will be analyzed and correlated with the results of the dNA scale. The effects of diagnosis and functional connectivity on cognitive outcomes (memory scores and other neuropsychological tests) will be examined using ANCOVA and regression models, including interaction effects and group-specific analyses. Additional regression analyses will assess differences in the relationship between cognitive performance and connectivity metrics. Age, handedness, and education will be included as covariates. This phase will receive scientific support from the University of Leuven (Dr. Dante Mantini) and the Cleveland Clinic (Dr. Filippo Cieri); however, these institutions and their respective researchers will not have access to the data.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 265 is above the median of 150 across 997 observational studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Neuromed IRCCS is the lead sponsor of 81 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Each of the 8 participating centers will enroll approximately at least 30 participants, specifically:
Inclusion Criteria (Stage #1):
Inclusion criteria (Stage #2 \& Stage #3):
Cognitively healthy individuals (HC):
Individuals with Subjective Memory Complaints (SMC):
Individuals with Mild Cognitive Impairment (MCI):
Individuals with probable Alzheimer's disease (AD):
Exclusion criteria (Stage #1):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Healthy older adults (HC) aged ≥ 65 years residing in Italy. No diagnosis of depression, mild cognitive impairment or any form of dementia.
Older adults with subjective memory complaints (SMC) aged ≥65 years, residing in Italy, who report or perceive subjective memory decline. This subjective memory complaint may occur with or without objective evidence of memory impairment and may be reported by the individual, a family member, or a clinician. Individuals with SMC should be excluded if they have a diagnosis of depression, mild cognitive impairment, or any form of dementia.
Older adults diagnosed with mild cognitive impairment (MCI), aged ≥65 years and residing in Italy, characterized by subjective cognitive decline (reported by the individual, a family member, or a clinician), objective cognitive impairment (as assessed by the Wechsler Memory Scale Logical Memory II), and relatively preserved activities of daily living. Individuals with MCI should be excluded if they have a diagnosis of depression or any form of dementia.
Older adults diagnosed with probable Alzheimer's disease (AD), aged ≥65 years, residing in Italy. Individuals with probable AD exhibit a decline in performance compared to their previous level of functioning, as reported by a caregiver (often a family member), along with objective evidence of episodic memory impairment on the Wechsler Memory Scale Logical Memory II.
Italian Validation and Factor Structure of the dynamic Neurocognitive Adaptation Scale (dNA)
The primary outcome of this study is the successful Italian validation of the dNA scale. Specifically, investigators expect to replicate the results of the English-language version (Cieri et al., accepted), with a four-factor structure, no multicollinearity (r \< 0.95) or insufficient common variance (r \< 0.3), satisfactory Kaiser-Meyer-Olkin (KMO) indices (\>0.70), significant Bartlett's sphericity test (\<0.01), and high internal consistency as indicated by Cronbach's alpha (\>0.80).
Time frame: From enrollment until the completion of dNA scale administration at the time of enrollment.
Association Between Activity Engagement, Temporal Maintenance, and Educational Attainment
Investigators expect that greater engagement in the activities under investigation, as well as their dynamic maintenance over time, reflected in higher dNA scale scores, will be positively associated with higher educational attainment.
Time frame: From enrollment until the completion of dNA scale administration and demographic assessment at the time of enrollment.
Association Between dNA scale and Neuropsychological Measures
Investigators expect that higher dNA scale scores will be positively associated with better neuropsychological performance, particularly in episodic memory and executive function domains. Specifically, cognitive performance will be assessed using a standardized battery, including the MMSE (or MoCA) for global cognition, Rey Auditory Verbal Learning Test (RAVLT) for verbal long-term memory, Trial Making Test (TMT) Form B for executive functioning, Digits Forward and Backward subtests (WAIS or WAIS-III) for working memory, Wechsler Memory Scale Logical Memory II (or Prose Memory), and Stroop Test for cognitive inhibition and information processing speed. These measures will provide both an overall cognitive assessment and domain-specific outcomes, which will be further explored for their expected association with the dNA scale scores.
Time frame: From enrollment until the completion of dNA scale administration and the neuropsychological assessment.
Association Between dNA scale and Structural and Functional Brain Organization
This outcome measure evaluates the relationship between dNA scale scores and functional brain network activity and organization derived from functional magnetic resonance imaging (fMRI). Within diagnostic groups (SMC, MCI, AD), higher scores on the dNA scale are hypothesized to be associated with increased activation and greater functional segregation within the task-negative network (default network, DN), alongside greater deactivation in task-positive networks, including the dorsal attention network (DAN) and the frontoparietal control network (FPCN). Functional connectivity analyses will be used to quantify both within-network segregation and between-network integration. These neuroimaging-derived metrics will be statistically associated with dNA scale scores using appropriate regression models within each diagnostic group.
Time frame: From enrollment until the completion of dNA scale administration and the neuroimaging acquisition. Structural MRI and functional MRI will be conducted at baseline if not already available from the participant registry.
Association Between dNA scale and Biomarkers of Pathological Aging
This additional outcome measure will evaluate the relationship between dNA scale scores and previously collected biomarkers, contingent upon data availability. Indeed, participating centers that have the capability may also retrieve information from the participant's medical record regarding biomarkers of pathological aging (e.g., APoE). Potential association between dNA scale scores and previously collected biomarkers will be further explored, within the healthy elderly sample and each diagnostic group (SMC, MCI, AD).
Time frame: From enrollment until the completion of dNA scale administration and retrieval of relevant information from the participant's medical record.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Undecided
Start is estimated for Sep 2026; primary completion for Nov 2027, 14 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Neuromed IRCCS