The Effects of a Hungarian Multidomain Lifestyle Intervention on Brain Health in Older Adults

Multi-echo functional MRI (3T Siemens Prisma scanner) measure of individual large-scale brain network segregation as well as network-specific within and cross-network connectivity changes will be derived. Network segregation will be estimated by computing the difference between within-network connectivity and between-network connectivity, normalised by the total connectivity.

Resting-state neural activity will be recorded via a 64-channel Brain Products actiCAP EEG device.

Individual-level periodic and aperiodic α peak frequency will be computed.

Cortical and subcortical resting-state multi-echo fMRI effective connectivity of brain regions associated with reward and motivation will be estimated using dynamic causal modelling.

Cortical and subcortical resting-state multi-echo fMRI effective connectivity of the default mode network will be estimated using dynamic causal modelling.

The volumes of the hippocampal subfields will be computed using proton density-weighted MRI.

The volumes of the striatal nuclei will be derived from T1 weighted MRI.

The integrity of the substantia nigra-ventral tegmental area (SN-VTA) and locus coeruleus (LC) will be computed based on magnetization transfer-weighted MRI.

Individual brain age will be estimated using T1-weighted MRI images utilising pre-trained deep neural networks specifically trained for brain age prediction.

The relative contribution of resting-state EEG frequency band measures will be computed (alpha, beta, delta, theta frequency bands).

Changes in feedback-related EEG (early and late feedback components, P300 and Error-related Negativity ERPs) and pupil responses will be measured during the Probabilistic Reversal Learning Task. During this task, participants have to choose between two abstract symbols. In the reward condition, participants receive positive (reward, +1 point) and neutral (zero point) feedback. In the punishment conditions, participants receive negative (punishment, -1 point) or neutral feedback. Participants complete 2 blocks of 80 trials of each condition (a total of 320 trials). In any given trial, one symbol is associated with a high (80%) and the other with a low (20%) probability of reward or lack of punishment. A reversal in reward contingencies is introduced 3-7 times per block. Participants are instructed to maximise the number of points earned throughout the experiment and are financially compensated based on their performance in the task.

Changes in the subjective cost of cognitive effort will be measured using the Cognitive Effort Discounting Paradigm.

Global cognitive function will be assessed using a composite score, which will be derived from a series of neuropsychological tests, including Verbal Episodic Memory Test, Location Learning Test, Digit Span, Verbal Fluency, Trail-Making Test, Victoria Stroop Test, and Digit Symbol Substitution Test. Scores from each test will be transformed into z-scores and then averaged to create a composite score. Higher scores indicate better performance.

Episodic Memory will be a composite score obtained from the Verbal Episodic Memory Test and the Location Learning Test. The Episodic Memory composite is calculated in the same way as the composite score for global cognitive function.

Executive Function will be a composite score obtained from Digit Span, Digit Symbol Substitution, Trail Making Test Part B, Victoria Stroop Test, and Verbal Fluency. The Executive Function composite is calculated in the same way as the composite score for global cognitive function.

Processing Speed will be a composite score obtained from Digit Symbol Substitution and Trail Making Test Part A. The Processing Speed composite is calculated in the same way as the composite score for global cognitive function.

Inflammatory cytokines, C-reactive protein, glial fibrillary acidic protein, Clustering, Brain Derived Neurotrophic factor, Insulin Growth Factor-1

Waist circumference (cm) will be measured.

Body Mass Index (BMI) is a measure of body fat based on height and weight for adult men and women. BMI will be expressed in kg/m^2.

Systolic blood pressure (mmHg) will be recorded using calibrated blood pressure monitors.

Diastolic blood pressure (mmHg) will be recorded using calibrated blood pressure monitors.

Hand grip strength will be quantified using a hand dynamometer, with higher values indicating greater muscle strength.

Physical performance will be assessed using the Short Physical Performance Battery (SPPB), which assesses balance, mobility, and muscle strength in older adults. The total score is the sum of the three components and ranges between 0 and 12, with higher scores indicating a better outcome. Only individuals with a score ≥ 1 in each subtest will be included in the study.

Subjective physical activity will be assessed using the International Physical Activity Questionnaire (IPAQ). It measures the types of PA intensity and time spent sitting that individuals do as part of their daily lives. Total subjective PA will be assessed in MET-min/week and time spent sitting will be assessed in min/day.

Changes in physical activity will be objectively measured using the Polar Pacer smart watch. Participants will be asked to wear the watch for 7 consecutive days every 2 months during the intervention. The device will track participants' heart rate, heart rate variability (calculated from pulse lengths), and MET (Metabolic Equivalent of Task).

Sleep will be tracked via the Polar Pacer smart watch. Participants will be asked to wear the watch for 7 consecutive days every 2 months during the intervention. The device will monitor participant's total sleep duration, the time spent in REM sleep, deep sleep, and light sleep as well as the percentage of each of the three sleep stages compared to total sleep time. The watch will also estimate the amount of interrupted sleep and a total sleep score per night (ranging from 1 to 100).

Subjective sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI). The global score ranges from 0 to 21, with higher scores indicating worse sleep quality.

The Athens Insomnia Scale (AIS) will be employed to assess the severity of insomnia. The total score ranges between 0 and 24, with higher scores indicating a more severe sleep disorder.

Depressive symptoms will be evaluated using the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire (PHQ-9). The GDS score ranges from 0 to 15, while the PHQ-9 provides a severity score ranging from 0 to 27. A score of ≥ 5 on either scale is indicative of the presence of depressive symptoms.

Well-being will be measured using the Hungarian version of the WHO Well-Being Questionnaire (WBI-5). The score can range from 0 to 15 points. A higher score indicates a greater degree of positive psychological well-being.

Perceived social support of the individual from the family, friends, and significant others will be assessed using the Multidimensional Scale of Perceived Social Support (MSPSS). The total score on the MSPSS ranges from 10 to 50, with higher scores indicating greater perceived social support.

A self-reported lifestyle questionnaire will be completed, collecting information about social life, mental activities, eating habits, subjective memory, and health status.

The SARC-F questionnaire will be employed as a screening tool for sarcopenia. The scores range from 0 to 10, with a cutoff of ≥ 4, indicating the presence of sarcopenia.

Weighted sum of the following dementia risk factors: age, sex, educational level in years, total cholesterol, physical activity status, systolic blood pressure, BMI, and diabetes. Higher scores indicate an increased risk for dementia.

Individuals will be asked to provide information about their sociodemographic (age, sex, ethnicity), education, and employment status, as well as their family (dementia) and medical history (head injury, diabetes, sleep apnoea, cardiovascular diseases, COVID-19 history and vaccination), medication and substance use (smoking, alcohol).

The Lawton IADL will be used to assess the individual's functional ability to perform daily tasks such as shopping, preparing meals, taking medication, and managing finances. Scores range from 0 to 8, with higher scores indicating better performance, i.e., more independent functionality.

The Mini-Mental State Examination (MMSE) will be used as a rapid screening instrument for dementia. It measures multiple cognitive domains, such as orientation, memory, attention and calculation, executive functions, visuospatial skills, abstraction. The scores range between 0 and 30, with the score of less than 26 indicating cognitive impairment. Participants who score below this cutoff will be excluded from this study.