Age-related Cognitive DeclineIN TeMPONCT06248723
ItaliaN Study With Tailored Multidomain Interventions to Prevent Functional and Cognitive Decline in Community-dwelling Older Adults
A study testing Nutritional intervention, Physical exercise and Cognitive training in people with Age-related Cognitive Decline, run by University of Milano Bicocca at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Age-related Cognitive Decline
- What is being tested?
- Nutritional intervention, Physical exercise and Cognitive training
- Type of treatment
- Vaccines, Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,340 participants
- Where
- 1 siteItaly
- Study dates
- 16 Jul 2024to Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)*
Show all 14Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS San Gerardo dei Tintori
Monza
Carlo Ferrarese, carlo.ferrarese@unimib.it
About this study
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.
Read the 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.
- Conditions
- Age-related Cognitive Decline
- Being tested
- Nutritional intervention, Physical exercise, Cognitive training, Oral hygiene, Sleep quality
- Keywords
- Cognitive decline, Dementia, Aging
- Medical subject headings
- Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutritional interventionOther
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 specific dietary patterns that can be individualized based on weight, comorbidities and personal preferences.
The need for weight loss or gain will be assessed on an individual basis. Dietary interventions will include group and individual sessions, and will be conducted by dietitians and nutritionists in a harmonized manner among the centers. The first meeting will be in-person and will be held at the subject's clinical center of enrollment. Follow-up will be conducted through online meetings.
Physical exerciseOther
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.
Cognitive trainingOther
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 (about six months), at least three times a week.
Oral hygieneOther
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.
Sleep qualityOther
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 raised from the medical history, participants will be referred to the relevant specialists for diagnosis and treatment of such problems.
Control of cardiovascular, metabolic, and infectious risk factorsOther
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.
Pharmacological evaluationOther
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.
SocializingBehavioural
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 interventions, for example through:
- Physical activity in groups or pairs, including dance or choir activities where possible
- Opportunities for further cognitive stimulation in groups through games (e.g., chess, cards, etc.)
- Proposal to cook, eat or shop together
- Group sessions with dietitian
Self-administered interventionsOther
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 of social activity, information on cardiovascular risk factors, as well as sleep, oral hygiene will be explained.
Subjects will therefore be treated as per normal clinical practice, albeit with the help of dedicated apps and counseling session.
| Study group | Role | What they receive |
|---|---|---|
| Active intervention arm | Experimental | * Physical exercise regime
* Mediterranean diet-based nutritional plan
* Cognitive training
* Regular medical check-ups
* Oral hygiene treatments and counseling
* Counseling on sleep hygiene and treatment
* Control of cardiovascular, metabolic, and infectious risk factors
* Adjustment of drug therapy
* Suggestions for improving social interactions
Physical exercise and cognitive training interventions will be monitored and partially administered through wearable devices and digital tools. Sleep quality will be monitored through wearable devices. Social interactions will be encouraged through a validated app. Receives: Other: Nutritional intervention; Other: Physical exercise; Other: Cognitive training; Other: Oral hygiene; Other: Sleep quality; Other: Control of cardiovascular, metabolic, and infectious risk factors; Other: Pharmacological evaluation; Behavioral: Socializing |
| Self-administered intervention arm | Active comparator | 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.
In addition, participants randomized to the self-guided intervention will receive an initial 30-60 minute counseling session on all domains covered by the study, in which guidelines for healthy diet, physical and cognitive activity, benefits of social activity, information on cardiovascular risk factors, as well as sleep, oral hygiene will be explained.
Subjects will therefore be treated as per normal clinical practice, albeit with the help of dedicated apps and counseling session. Receives: Other: Self-administered interventions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Neuropsychological Test Battery (mNTB) score
Participants will be scored through the mNTB to assess their cognitive state at baseline and cognitive changes at follow-ups. The mNTB score is a composite score for a battery of 14 tests total. The outcome measure is a z-score, it has no minimum or maximum value. A higher score means a better outcome.
Measured: 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 outcomes (32)
Short Physical Performance Battery (SPPB) score
Minimum score: 0, maximum score: 12, a higher score means a better performance.
Measured: 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 needed to walk 4 meters (in seconds). A higher time means a worse performance.
Measured: 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
Walking speed (in meters per second). A higher speed means a better performance.
Measured: 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
Hand grip strength measured (in kilograms) with a hand dynamometer. A higher result means a better performance.
Measured: 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
Minimum score: 0, maximum score: 6, a higher score means a better performance.
Measured: 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
Minimum score: 0, maximum score: 8, a higher score means a better performance.
Measured: 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
Minimum score: 0, maximum score: 100, a higher score means a better performance.
Measured: 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
Minimum score: 14, maximum score: 98, a higher score means a better outcome.
Measured: The score will be taken at baseline, at Month 6, Month 12, and Month 18 follow-ups.
Number of falls taken
A higher number of falls means a worse outcome.
Measured: Through study completion, an average of 2 years.
Number of hospital admissions
A higher number of hospital admissions means a worse outcome.
Measured: Through study completion, an average of 2 years.
Number of visits to general practitioner
The number does not indicate a better or worse outcome. It is only informative.
Measured: Through study completion, an average of 2 years.
Geriatric Depression Scale (GDS) score
Minimum: 0, maximum: 15, a higher score indicates a worse outcome.
Measured: 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.
UCLA Loneliness Scale (UCLA-LS) score
Minimum: 20, maximum: 80, a higher score indicates a worse outcome.
Measured: 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.
Psychological General Well Being Index (PGWBI) score
Minimum: 0, maximum: 110, a higher score indicates a worse outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Physical Health
Minimum: 0, maximum: 100, a higher score means a better outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Psychological Health
Minimum: 0, maximum: 100, a higher score means a better outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Social Relationships
Minimum: 0, maximum: 100, a higher score means a better outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Environment
Minimum: 0, maximum: 100, a higher score means a better outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Quality of Life
Minimum: 1, maximum: 5, a higher score means a better outcome.
Measured: 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Health Satisfaction
Minimum: 1, maximum: 5, a higher score means a better outcome.
Measured: 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.
Pittsburgh Sleep Quality Index (PSQI) score
Minimum: 0, maximum: 21, a higher score means a worse outcome.
Measured: 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.
Mini Nutritional Assessment-Short Form (MNA-SF) score
Minimum: 0, maximum: 14, a higher score means a better outcome.
Measured: 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.
Mediterranean Diet Scale (MDScale) score
Minimum: 0, maximum: 9, a higher score means a better outcome.
Measured: 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.
Framingham Risk Score
Measured in percentage %, 0-100%. A higher percentage indicates a higher cardiovascular risk (worse outcome).
Measured: 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.
Cognitive Reserve Index questionnaire (CRIq) score
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Intrinsic Motivation Inventory (IMI) score
Minimum: 45, maximum: 315, a higher score means a better outcome.
Measured: 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.
Number of incidental diagnoses of Mild Cognitive Impairment (MCI) and dementia, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
A higher number means a worse outcome.
Measured: Through study completion, an average of 2 years.
Composite score of processing speed and attention
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Composite score of executive functions
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Composite memory score
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Composite language score
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Composite score of general cognitive assessment
z-score without a maximum or minimum value, a higher z-score means a better outcome.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2024
- Study start16 Jul 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Age-related Cognitive DeclineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The patients are randomized 1:1 into "active intervention" and "self-guided intervention" parallel groups.
- Masking
- None (open label)
- Enrolment
- 1,340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06248723
- Sponsor's protocol ID
- IN TeMPO
- Acronym
- IN TeMPO
- Status last verified
- Jul 2025
- First submitted
- 27 Dec 2023
- Last updated
- 29 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 biomarkers to target and monitor multidimensional prevention of cognitive and functional decline (nested in the IN-TeMPO study framed within the world-wide FINGERS network). Front Aging Neurosci. 2025 May 7;17:1581892. doi: 10.3389/fnagi.2025.1581892. eCollection 2025.
PubMed 40400914
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ItaliaN Study With Tailored Multidomain Interventions to Prevent Functional and Cognitive Decline in Community-dwelling Older Adults
- ClinicalTrials.gov ID
- NCT06248723
- Acronym / sponsor ID
- IN TeMPO / IN TeMPO
- Conditions
- Age-related Cognitive Decline
- Keywords
- Cognitive decline, Dementia, Aging
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,340 participants (estimated)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Collaborators
- European Union
- Study start
- 16 Jul 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 8 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The patients are randomized 1:1 into "active intervention" and "self-guided intervention" parallel groups.
| Arm | Type | Receives |
|---|---|---|
| Active intervention arm | Experimental | Other: Nutritional intervention, Other: Physical exercise, Other: Cognitive training, Other: Oral hygiene, Other: Sleep quality, Other: Control of cardiovascular, metabolic, and infectious risk factors, Other: Pharmacological evaluation, Behavioral: Socializing* Physical exercise regime * Mediterranean diet-based nutritional plan * Cognitive training * Regular medical check-ups * Oral hygiene treatments and counseling * Counseling on sleep hygiene and treatment * Control of cardiovascular, metabolic, and infectious risk factors * Adjustment of drug therapy * Suggestions for improving social interactions Physical exercise and cognitive training interventions will be monitored and partially administered through wearable devices and digital tools. Sleep quality will be monitored through wearable devices. Social interactions will be encouraged through a validated app. |
| Self-administered intervention arm | Active comparator | Other: Self-administered interventionsSubjects 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. In addition, participants randomized to the self-guided intervention will receive an initial 30-60 minute counseling session on all domains covered by the study, in which guidelines for healthy diet, physical and cognitive activity, benefits of social activity, information on cardiovascular risk factors, as well as sleep, oral hygiene will be explained. Subjects will therefore be treated as per normal clinical practice, albeit with the help of dedicated apps and counseling session. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nutritional interventionThe 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 specific dietary patterns that can be individualized based on weight, comorbidities and personal preferences. The need for weight loss or gain will be assessed on an individual basis. Dietary interventions will include group and individual sessions, and will be conducted by dietitians and nutritionists in a harmonized manner among the centers. The first meeting will be in-person and will be held at the subject's clinical center of enrollment. Follow-up will be conducted through online meetings. | Other | Active intervention arm |
| Physical exerciseThe 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 | Active intervention arm |
| Cognitive trainingParticipants 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 (about six months), at least three times a week. | Other | Active intervention arm |
| Oral hygieneParticipants 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 | Active intervention arm |
| Sleep qualityDuring 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 raised from the medical history, participants will be referred to the relevant specialists for diagnosis and treatment of such problems. | Other | Active intervention arm |
| Control of cardiovascular, metabolic, and infectious risk factorsMeasurements 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 | Active intervention arm |
| Pharmacological evaluationEvaluation 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. | Other | Active intervention arm |
| SocializingTo 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 interventions, for example through: * Physical activity in groups or pairs, including dance or choir activities where possible * Opportunities for further cognitive stimulation in groups through games (e.g., chess, cards, etc.) * Proposal to cook, eat or shop together * Group sessions with dietitian | Behavioural | Active intervention arm |
| Self-administered interventionsSubjects 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 of social activity, information on cardiovascular risk factors, as well as sleep, oral hygiene will be explained. Subjects will therefore be treated as per normal clinical practice, albeit with the help of dedicated apps and counseling session. | Other | Self-administered intervention arm |
Primary outcome
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.
Participants will be scored through the mNTB to assess their cognitive state at baseline and cognitive changes at follow-ups. The mNTB score is a composite score for a battery of 14 tests total. The outcome measure is a z-score, it has no minimum or maximum value. A higher score means a better outcome.
32 secondary outcomes
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.
UCLA Loneliness Scale (UCLA-LS) 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.
Psychological General Well Being Index (PGWBI) 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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Physical Health
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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Psychological Health
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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Social Relationships
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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Environment
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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Quality of Life
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.
World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Health Satisfaction
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.
Pittsburgh Sleep Quality Index (PSQI) 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.
Mini Nutritional Assessment-Short Form (MNA-SF) 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.
Mediterranean Diet Scale (MDScale) 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.
Framingham Risk 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.
Cognitive Reserve Index questionnaire (CRIq) 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.
Intrinsic Motivation Inventory (IMI) 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.
Number of incidental diagnoses of Mild Cognitive Impairment (MCI) and dementia, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
Time frame: Through study completion, an average of 2 years.
Composite score of processing speed and attention
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.
Composite score of executive functions
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.
Composite memory 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.
Composite language 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.
Composite score of general cognitive assessment
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Derived from this study: PubMed 40400914Sala 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 biomarkers to target and monitor multidimensional prevention of cognitive and functional decline (nested in the IN-TeMPO study framed within the world-wide FINGERS network). Front Aging Neurosci. 2025 May 7;17:1581892. doi: 10.3389/fnagi.2025.1581892. eCollection 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nutritional intervention, Physical exercise and Cognitive training in people with Age-related Cognitive Decline, run by University of Milano Bicocca at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carlo Ferrarese (0392333595, carlo.ferrarese@unimib.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06248723, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.