ItaliaN Study With Tailored Multidomain Interventions to Prevent Functional and Cognitive Decline in Community-dwelling Older Adults

Overview

The goal of this interventional non-pharmacological study is to investigate the effects of a multi-domain intervention ( "active intervention"), compared to that followed by normal clinical practice ("self-guided intervention"), in older adults. The primary objective is whether these interventions can prevent functional and cognitive decline in at-risk subjects. The multi-domain interventions will include physical exercise, a Mediterranean diet-based nutritional plan, cognitive training, regular medical check-ups, oral hygiene treatments and counseling, monitoring and counseling on visual and auditory abilities, counseling on sleep hygiene and treatment, control of cardiovascular, metabolic, and infectious risk factors, adjustment of drug therapy, suggestions for improving social interactions.

Detailed description

The study is multicentric and will include 10 centers. Patients will be enrolled either through their General Practitioners (GPs), which will then refer back to their reference centers, or through the centers themselves.

Patients will undergo a screening visit, which will include a multi-faceted evaluation of cognitive function, physical and functional efficiency, and cardiovascular and cognitive decline risk factors. Procedures to be carried out during the screening visit include:

* Collection of socio-demographic data (age, sex, marital status, cohabitation, level of education, social interactions), clinical details (medical and medication history), and evaluation of inclusion/exclusion criteria * Assessment of the degree of frailty through the Primary Care Frailty Index (PC-FI) * Assessment of the presence of increased risk of developing dementia through the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score * Assessment of cognitive performance through the General Practitioner assessment of COGnition (GPCOG) * Assessment of cognitive performance through the Rey Auditory Verbal Learning Test - immediate * Assessment of functional status by Short Physical Performance Battery (SPPB) tests * Nonverbal interference tests * Assessment of cognitive performance through the Rey Auditory Verbal Learning online version (RAVL-T delayed) * Collection of self-administered scales for cognitive performance assessment through the Test Your Memory - Italian (TYM-I) scale.

Then, eligible patients will be enrolled for the second, active intervention phase of the study, which will include a baseline visit and 3 follow-up visits, at 6, 12, and 18 months.

During these visits, primary and secondary endpoint outcomes will be collected according to protocol.

Interventions

• Other Nutritional intervention
  The objectives of the dietary intervention will be in accordance with the principles of the Mediterranean diet. Weekly menus will be provided that ensure a balanced intake of the various nutrients, according to the objectives outlined in the study protocol, including a reduction in saturated fatty acids (with proportionately more mono- and polyunsaturated fatty acids), promotion of fiber sources and reduction of sugars, adequate protein and micronutrient intake. They will be accompanied by speci
• Other Physical exercise
  The physical activity protocol will be geared to the principles of progressive and individualized loading, in group sessions supervised by a physical therapist within gyms for the strength and balance training portion, and in moderate to intense aerobic activities based on individual preferences and characteristics. The physiotherapist will conduct an individual assessment and develop personalized programs for all participants. Exercise sessions will be held 2-3 times a week.
• Other Cognitive training
  Participants will be evaluated through a Cognitive and Psychological Assessment, which will allow measurement of each participant's cognitive functioning and well-being. Computerized cognitive training (CCT) using Brain HeadQuarter (BrainHQ) or similar software will be used as a cognitive intervention. The CCT includes game-based adaptive exercises that target attention, intelligence, memory, navigation, processing speed and social skills. The training will consist of 72 sessions for 24 weeks (a
• Other Oral hygiene
  Participants will be referred for evaluation at dental hygiene offices. As part of the study, participants will also undergo anticholinergic burden calculation, screening for risk factors for oral diseases (smoking, alcohol), and reduction in the frequency of sugar intake through dietary intervention will be sought. Participants will also undergo the Oral Health Assessment Tool rating scale.
• Other Sleep quality
  During the visits, participants' sleep will be assessed, either by clinical interview or by scales. Participants will also have the opportunity to assess their own sleep via wearable devices. If sleep hygiene issues are detected, advice based on currently available scientific evidence will be provided. If, on the other hand, a suspicion of sleep disorders, including, for example, obstructive sleep apnea syndrome, restless legs syndrome, insomnia, or Rapid Eye Movement (REM) sleep disorder, is r
• Other Control of cardiovascular, metabolic, and infectious risk factors
  Measurements of blood pressure, weight, BMI, abdominal circumference, and advice on health promotion and healthy lifestyle will be provided. Recommendations on adherence to the Piano Nazionale di Prevenzione Vaccinale (PNPV) will also be provided.
• Other Pharmacological evaluation
  Evaluation of prescriptive appropriateness (STOP\&START and Beers criteria) and calculation of anticholinergic burden (ACB calculator) will be carried out by a geriatrician, with rationalization of therapy and, where possible, de-prescribing.
• Behavioral Socializing
  To encourage socialization, proposed activities will be carried out as much as possible in groups of 10-12 people, and outdoor group activities will be suggested on a biweekly basis (e.g., walks in parks). On a monthly basis, the nurse and psychologist will organize motivational and check-up meetings (in recreation centers/via telematics) in order to promote adherence to the protocol, collect questions and stimulate participants. Social activity will also be implemented in the context of all in
• Other Self-administered interventions
  Subjects in the control group will receive regular health advice in the same domains as the intervention group, via dedicated app and/or access to the dedicated portal on the Age-It website. Such advice and information will be timed to encourage adherence. In addition, participants randomized to the self-guided intervention will receive an initial counseling session of 30-60 minutes on all domains covered by the study, where guidelines for healthy diet, physical and cognitive activity, benefits

Primary outcome measures

• Modified Neuropsychological Test Battery (mNTB) score [Time frame: The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6 follow up, Month 12 follow up, and Month 18 follow up. The tests take around 90 minutes overall.]

Secondary outcome measures (12)

• Short Physical Performance Battery (SPPB) score [Time frame: The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• 4-m gait speed test - time [Time frame: The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• 4-m gait speed test - speed [Time frame: The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• Hand grip test [Time frame: The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• Activities of Daily Living (ADL) index score [Time frame: The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups..]
• Instrumental Activities of Daily Living (IADL) scale score [Time frame: The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• Barthel Index score [Time frame: The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]
• 14-item Resilience Scale (RS-14) score [Time frame: The score will be taken at baseline, at Month 6, Month 12, and Month 18 follow-ups.]
• Number of falls taken [Time frame: Through study completion, an average of 2 years.]
• Number of hospital admissions [Time frame: Through study completion, an average of 2 years.]
• Number of visits to general practitioner [Time frame: Through study completion, an average of 2 years.]
• Geriatric Depression Scale (GDS) score [Time frame: The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.]

Eligibility criteria

Inclusion criteria

• Aged 60 or older
• Mild/moderate vulnerability (Primary Care Frailty Index score between 0.07 and 0.21)
• Cardiovascular risk factors, Ageing and Incidence of Dementia (CAIDE) > 6
• Clinical Dementia Rating (CDR) ≤ 0.5
• Presence of increased risk of developing dementia by family history (≥ 1 family member with dementia) and/or at least one modifiable risk factor, with Lifestyle Index ≥2. Lifestyle index evaluation: each "Yes" answer to the following questions = 1 point.

• Physical activity less than 2.5 hours per week (defined as physical activity intense enough to lead to sweating and breathlessness)\*
• Diet: less than 5 servings of fruits and vegetables per day\*
• Diet: less than 2 servings of fish per week\*
• Hypertension: diagnosed by a physician or on medication, or Systolic Blood Pressure (SBP)>140 mmHg, or Diastolic Blood Pressure (DBP)>90 mmHg)
• Diabetes: type 1 or type 2 diagnosed by a physician, or on medication, or HbA1C ≥7 % in the previous 6 months
• Sleep disturbances, depressive symptoms, or mental/physical stress symptoms, for at least 1 month, judged by the physician to be disabling in daily life
• BMI ≥ 25 kg/m\^2\*
• Alcohol: > 21 alcohol units/week\*. \*Based on international and WHO guidelines.
• Informed consent freely given and acquired before the start of the study

Exclusion criteria

• Diagnosis of dementia or suspected dementia following the screening visit
• CDR > 0.5
• Residents in residential facilities for the elderly
• Inability to consent to informed consent and/or actively participate in study interventions, according to clinical judgment
• Any condition that prevents safe involvement in the intervention and/or cooperation in the study. For example, a significant neurological or psychiatric condition, including but not limited to brain tumors (benign or malignant), major psychiatric disorders (e.g. current major depressive disorder, schizophrenia, schizoaffective disorder or bipolar disorder), recent brain hemorrhage (parenchymal or subdural), history of concussive head trauma with persistent or significant neurological outcomes, known morpho-structural abnormalities in the brain, active alcohol/drug abuse, active uncontrolled disease of any major organ system; history within the last six months of any acute disease of a major organ system requiring emergency care or hospitalization, including revascularization procedures; severe renal or hepatic insufficiency; unstable or poorly controlled diabetes mellitus, hypertension, or heart failure; malignant neoplasms within the past 3 years (except basal cell carcinoma or squamous cell carcinoma in situ of the skin or localized prostate adenocarcinoma in male participants); any clinically relevant abnormality in blood parameters; severe loss of vision, smar or communication ability, such as to prevent cooperation.
• Enrollment in other trials
• High performance on screening memory tests: RAVL-T immediate score >48 (score ranges 0-75), RAVL-T delayed >10 (score ranges 0-15)
• Planned transfers from the municipality of residence during the duration of the study for a duration longer than 2 weeks.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Italy · 1 center

• Fondazione IRCCS San Gerardo dei Tintori — Monza

Publications

• Sala G, Cuffaro L, Pozzi FE, Andreoni S, Bazzini C, Conti E, Zoia CP, Beretta S, Tremolizzo L, Bellelli G, Okoye C, Ferrara MC, De Luca A, Lenti R, Mantuano P, Pontrelli P, Stasi A, Defazio G, Solfrizzi V, Crudele L, Airoldi C, Chiaradonna F, Longhese MP, Messina G, Natalello A, Orlandi I, Aloisi A, Capone S, Ingannato A, Nacmias B, Capello D, Mangialasche F, Ferrarese C. Multi-pathway blood bioma PMID 40400914

Identifiers

NCT: NCT06248723 · IN TeMPO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗