Efficacy of a Multicomponent Intervention on Cognitive Function for the Caregiver-patient Dyad

It will be evaluated by the Montreal Cognitive Assessment (MoCA). The scale evaluates 6 domains: visuospatial ability, executive function, memory, attention/concentration, language, and orientation. It has a scoring scale from 0 to 30, with the following interpretation: 26 or more: No cognitive impairment. 20 to 23: Mild Cognitive Impairment. Score less than 10: major neurocognitive disorder

It will be evaluated by Mini Mental State Examination (MMSE). The scale evaluates the dimensions of orientation, memory, attention and calculation, memory, and language. It has a score of 0 to 30 points and can be categorically interpreted as follows: between 30 and 27 points: No cognitive impairment. Between 26 and 25 points: Possible cognitive impairment. Between 24 and 10 points: mild to moderate cognitive impairment. Between 9 and 6 points: moderate to severe cognitive impairment. Less than 6 points: Major cognitive impairment.

The change in verbal learning and memory will be assessed using the Hopkins Verbal Learning Test (HVLT). It consists of 12 words grouped into three semantic categories. In the population aged between 56 and 76 years, the mean total recall is 18.6 with a standard deviation of 4.6, while for delayed recall, the mean is 6.1 with a standard deviation of 2.4

The change in processing speed and visual attention will be evaluated using the Symbol Digit Modalities Test (SDMT). This test assesses two domains: processing speed and sustained attention. In the population aged between 56 and 76 years, the mean score is 27 (12.1)

The change in visual attention, thinking speed, and visuospatial ability will be evaluated using the Trail Making Test (TMT-Form A, TMT-Form B). Interpreting the results involves comparing completion times of these forms with normative data corresponding to the same age group. For context, the mean completion times for TMT-A and TMT-B in the population aged 56 to 75 years are as follows: 75.8 seconds (with a standard deviation of 22.8 seconds) for TMT-A and 178 seconds (with a standard deviation of 80.7 seconds) for TMT-B.

The Color and Word Test assesses executive functioning and selective attention, measuring processing speed and the ability to focus on relevant stimuli while discarding distractors. It also examines cognitive control, inhibition and resistance to cognitive interference. The mean scores for 'Word', 'Color', 'Word-Color' and 'Interference' are 77.7 (standard deviation 21.8), 55.5 (standard deviation 16.6), 30.8 (standard deviation 11.6) and -1.4 (standard deviation 9.1) respectively, reflecting the cognitive abilities of the tested group.

The change in perceptual organization and visual memory will be assessed through the Rey Complex Figure Test. This test is divided into 18 elements, each of which scores 2 if the execution is correct; if there is a mistake in the placement or tracing of the element, 1 point is awarded, and if both the placement and tracing are incorrect (or the element is absent), 0 points are awarded. Thus, the total possible score varies between 0 and 36. Two sets of scores are obtained: one for immediate copy and another for long-term recall. In the age group of 56 to 76 years, the mean score for the copying task is 27.9 with a standard deviation of 7.4, while for long-term memory, the mean is 13.7, also with a standard deviation of 7.4

Change in verbal fluency and executive functions will be assessed through the Semantic and Phonological Verbal Fluency Test. This test evaluates the ability to generate words following specific semantic or phonological criteria. Scores are assigned based on semantic category and the initial letter of words. For the letter "F," the mean is 9.9 with a standard deviation of 4.3; for "A," the mean is 10.1 with a standard deviation of 4.4; and for "S," the mean is 9.6 with a standard deviation of 4.4. In semantic categories, "ANIMALS" has a mean of 15.6 with a standard deviation of 4.5, while "FRUITS" has a mean of 13 with a standard deviation of 3.7. These scores reflect the quantity and variety of words individuals can produce and are indicative of their linguistic ability and executive capacity

The change in the levels of verbal naming and expression will be assessed from the BOSTON Naming Test. In the age group 56 to 76 years, the mean score for the copying task is 42.8 with a standard deviation of 8

TThe Token Test will be used to assess verbal comprehension. This test specifically measures skills related to listening comprehension and the ability to follow instructions.

As for the cut-off points for the different ages, they are set as follows: 50 to 56 years (31.5-32), 57 to 59 years (32-32.5), 60 to 68 years (32-32.5), 69 to 71 years (31-31.5), 72 to 74 years (31.5-32.5).

It is designed to evaluate attention and working memory. It consists of a total of 8 items distributed in two trials. This task is divided into two parts: one that requires repeating the numbers in the order in which they are presented (direct order) and another in the reverse order.

For individuals between 50 and 71 years of age, the cut-off points for correct retention are 4 in the direct order and 3 in the reverse order. These thresholds indicate the minimum number of digits that the individual must remember correctly to be considered within a normal range of functioning in each task modality

The patient's independence will be assessed using the Lawton and Brody scale. This scale evaluates functional capacity with 8 items: "ability to use the telephone, shop, prepare food, take care of the house, wash clothes, use transportation, and responsibility regarding medication and administration of their finances." Each item is rated between 0 (dependent) and 1 (independent), and the total score ranges from 0 to 8, reflecting the time required to perform these activities.

It will be evaluated using the Linda Fried Frailty Scale, four criteria will be taken: poor physical activity, self-report of physical fatigue, unintentional weight loss, and muscle weakness (estimated by grip strength). The results are interpreted as follows: No criteria = robust, 1 or 2 criteria = pre-frail, 3 or more criteria = frail

The nutritional status will be assessed through the Mini Nutritional Assessment (MNA) scale. This scale includes six items: loss of appetite, recent weight loss, mobility, presence of acute illness or psychological stress in the last three months, presence of neuropsychological problems, and body mass index. A score between 12-14 points indicates normal nutritional status, 8-11 points signify a risk of malnutrition, and 0-7 points indicate malnutrition. For a more detailed assessment, three additional items will be evaluated, including whether the patient lives independently, takes more than 3 medications per day, and has skin injuries, through a dichotomous scale of Yes or No

It will be evaluated with the Tinetti Scale. This scale consists of 2 dimensions: mobility and balance, distributed in 9 items. A score of less than 19 points in both dimensions will imply a high risk of falls, a score of 19 to 24 will reflect a medium risk of falls and a score of 25 to 28 will indicate a low risk of falls

The assessment will be conducted using the Senior Fitness Test, which consists of six tests grouped into five categories: muscular strength, flexibility, aerobic capacity, agility, and balance.

Muscular strength is evaluated with two tests: the chair stand test and the arm curl test. Flexibility is assessed using the chair sit-and-reach test and the back scratch test. Aerobic capacity can be evaluated with either the 6-minute walk test or the 2-minute step test. Agility and balance are assessed with the up-and-go test.

The test scores depend on the participant's gender and age.

Changes in bacterial communities and their metabolites will be assessed using 16S rRNA sequencing for microbiota analysis and both targeted and non-targeted metabolomic approaches for metabolite profiling in blood and stool samples, using mass spectrometry as an analytical technique. This test will be performed on a random sample of patients.

The caregiver overload is assessed through the Zarit Burden Interview-ZBI, which analyzes the subjective experience of the burden perceived by the caregiver. The scale includes 22 items, scored on a Likert scale of frequency ranging from 1 to 5 points. The total score on the scale can range from 22 to 110 points, with the following categorization: < 46 points: No overload, 46 to 56 points: Mild overload, 57 or more points: Intense overload.

Social support will be determined using the Medical outcomes study social support survey (MOS-SSS). This instrument includes 20 items organized into 4 dimensions: Emotional support, instrumental support, positive social interaction, and affective support. It utilizes a 5-point Likert scale. All items are rated on a 5-point Likert frequency scale. The total score for the global social support index can range from 19 to 95 points, with the following categories: Maximum 95 points, medium 57 points, and minimum 19 points. Low overall social support: <57 points.

Quality of life will be measured through the SF-36 questionnaire applied to the dyad. It consists of 36 questions, in 8 dimensions: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health of the patient. The score is transformed into a scale with a range from 0 (worst health status) to 100 (best health status) and a summary calculation of two dimensions (physical and mental) using the weighted sum of the scores of the eight dimensions.

To evaluate the feasibility, acceptability, and adherence of the intervention as a primary outcome, some dimensions proposed by Gadke et al as recruitment rates, retention rates, social validity, practicality, and, adherence or the intervention.