Background Dementia affects tens of millions of people and no curative therapy exists.
Non-pharmacological interventions that are safe, scalable, and acceptable are therefore
essential to delay decline and preserve functioning. Positive Psychology Interventions
(PPIs) have shown promising effects on wellbeing and, more recently, on cognitive
performance and neural markers in older adults with early cognitive decline. Positive
Neuropsychology proposes that cultivating positive traits and eudaimonic wellbeing may
support brain plasticity and cognitive control through multiple pathways, including
increased engagement, motivation, and adoption of protective lifestyles. Building on this
framework, the present trial tests an online, multi-component PPI tailored for adults
with Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI). The program
is designed to be feasible, scalable, and low-risk, and to generate clinically relevant
outcomes on cognition and brain functioning.
Objectives and Hypotheses Primary objective: determine whether the PPI produces greater
improvements than Treatment As Usual (TAU) in (a) cognitive performance and (b)
neurophysiological indices of brain functioning at post-intervention and at 9-month
follow-up. Secondary objectives: evaluate effects on wellbeing and related psychosocial
constructs (character strengths, mindfulness), and assess feasibility, adherence, and
safety of online delivery. We hypothesize larger gains with PPI at 16 weeks and sustained
benefits at follow-up, with potentially stronger effects in SCD than MCI.
Study Design and Setting Randomized, parallel-group, superiority behavioral trial with
two diagnostic groups (SCD, MCI) recruited via Alzheimer Hellas. Within each cohort,
participants are randomized 1:1 to PPI or TAU, yielding four arms (SCD-PPI, SCD-TAU,
MCI-PPI, MCI-TAU). Randomization is concealed and performed by site personnel who are not
involved in outcome assessment. The trial is minimal risk, uses no FDA-regulated
products, and is approved by the Bioethics Committee of Alzheimer Hellas (Approval No.
99/5-6-2024). Outcome assessors are trained and, where feasible, blinded to assignment.
Participants Community-dwelling older adults with a documented diagnosis of SCD or MCI
from Alzheimer Hellas according to site procedures are eligibl. Key capabilities include
informed consent, sufficient sensory ability for testing, and access/ability to join
online groups. Major neurological/psychiatric conditions that would confound outcomes,
severe sensory impairment preventing testing, and concurrent participation in similar
psychological programs during the trial are excluded. After consent, participants receive
unique study IDs; identifiers are stored separately, with controlled access, and
destroyed after data lock.
Intervention: Multicomponent Positive Psychology Program Delivery: weekly small-group
videoconference sessions (~60 minutes) for 16 weeks led by trained psychologists.
Assessment schedule and procedures
Assessments occur at four time points:
T0 baseline (pre-randomization); T1 mid-intervention (6 weeks); T2 post-intervention
(16 weeks; primary endpoint); T3 follow-up (~9 months post-T2). Attendance and
home-practice adherence are tracked. Adverse events (AEs) are monitored each visit and
during sessions per institutional policy.
Outcomes and Data Acquisition
Primary outcomes (analyzed from T0 to T3):
Cognitive performance: a composite derived from the REMEDES4Alzheimer computerized
battery capturing episodic memory, working memory, attention subdomains, and executive
functions, with minimized demographic bias.
Brain functioning: EEG and functional near-infrared spectroscopy (fNIRS) markers obtained
during standardized cognitive tasks using harmonized acquisition and artifact-handling
protocols.
Secondary outcomes: validated indices of wellbeing (PERMA-Profiler; PANAS) measured at
all time points to model trajectories. Exploratory psychosocial measures include
character strengths (VIA-114GR) and mindfulness (MAAS). Feasibility metrics include
recruitment and retention, session attendance, and self-reported practice.
Sample Size and Power Four arms (SCD-PPI, SCD-TAU, MCI-PPI, MCI-TAU). A priori power
calculations indicate a minimum of 32 participants per arm; target enrollment N=128.
Data management and quality control Data are captured on secure, password-protected
platforms under unique study IDs; personally identifying information is maintained in a
separate, access-restricted file. Quality procedures include range and logic checks,
double verification of key variables, and standardized preprocessing pipelines for
EEG/fNIRS feature extraction. After database lock, the re-identification log is
destroyed. De-identified data may be shared as described in the IPD plan.
Statistical analysis Analyses follow the intent-to-treat principle with participants
analyzed as randomized. For longitudinal outcomes, linear mixed-effects models estimate
change and Arm×Time interactions, with random intercepts for participants and adjustment
for diagnosis cohort (SCD/MCI) and prespecified covariates (e.g., age, sex, baseline
value). The two primary outcomes will be tested with appropriate multiplicity control.
EEG/fNIRS features are derived via prespecified pipelines and analyzed analogously.
Exploratory mediation models will assess whether changes in mindfulness or strengths use
relate to cognitive and neural changes.
Safety and ethics Risks are minimal (time burden; potential fatigue during EEG and
fNIRS). Standardized procedures and scheduled breaks mitigate burden. AEs are recorded,
assessed for relatedness and severity, and reported to the ethics committee per policy.
The study complies with the Declaration of Helsinki and applicable data-protection laws.
Implementation and expected impact Remote delivery enhances access for older adults with
mobility or caregiving constraints and lowers cost for participants and providers. If
efficacious, the program can be scaled across community and clinical settings through
brief facilitator training and manualized materials. The trial will provide mechanistic
evidence on whether cultivating character strengths and mindfulness improves cognitive
functioning and alters neural activity in early decline. Demonstration of sustained
benefits at nine months would support PPIs as practical, low-risk adjuncts to usual care
for SCD and MCI, with potential to delay progression.
Follow-up and data sharing All participants are invited to T3 follow-up to assess
durability. De-identified datasets may be shared on reasonable request after publication,
subject to approvals and data-use agreements, consistent with the IPD sharing plan.
