The Effects of Multidomain Non-pharmacological Interventions on the Elderly With or Without Mild Cognitive Impairment

MMSE using the Chinese version revised by Zhang Mingyuan, the scale includes 30 items, including orientation, instantaneous memory, attention, computation, recall, language and visuospatial. The MMSE score ranges from 0 to 30 (30=best).

MMSE using the Chinese version revised by Zhang Mingyuan, the scale includes 30 items, including orientation, instantaneous memory, attention, computation, recall, language and visuospatial. The MMSE score ranges from 0 to 30 (30=best).

Auditory Verbal Learning Test（AVLT）to rate immediate (sum of words recalled on the 5 learning trials) and delayed episodic verbal memory.

Auditory Verbal Learning Test（AVLT）to rate immediate (sum of words recalled on the 5 learning trials) and delayed episodic verbal memory.

Logic memory test (LMT): which assesses memory for brief passages, similar to newspaper stories. Subjects were assessed on immediate recall and 30 minute interval for delayed recall, according to standard practice. Subjects were not instructed in advance that they would be re-tested on the story after a delay of 30 minutes.

Logic memory test (LMT): which assesses memory for brief passages, similar to newspaper stories. Subjects were assessed on immediate recall and 30 minute interval for delayed recall, according to standard practice. Subjects were not instructed in advance that they would be re-tested on the story after a delay of 30 minutes.

The trail marking test A (TMT-A): The TMT-A consisted of a standardized page on which the numbers 1 to 25 are scattered within circles, and the participants were asked to connect the numbers in order as quickly as possible. A maximum time of 300 seconds was allowed before discontinuing the test. Direct scores of TMT-A were the time in seconds taken to complete task.

The trail marking test A (TMT-A): The TMT-A consisted of a standardized page on which the numbers 1 to 25 are scattered within circles, and the participants were asked to connect the numbers in order as quickly as possible. A maximum time of 300 seconds was allowed before discontinuing the test. Direct scores of TMT-A were the time in seconds taken to complete task.

Digit Symbol Substitution Test (DSST): The DSST was used to assess visual search, and perceptual and graphomotor speed. The number of correct substitutions during a 90-second interval was used as the score.

Digit Symbol Substitution Test (DSST): The DSST was used to assess visual search, and perceptual and graphomotor speed. The number of correct substitutions during a 90-second interval was used as the score.

Digit Span Test (DST): including digit span forwards (DSF) and digit span backwards (DSB)

Digit Span Test (DST): including digit span forwards (DSF) and digit span backwards (DSB)

Barthel index:The main aim is to establish degree of independence from any help, physical or verbal, however minor and for whatever reason.

Barthel index:The main aim is to establish degree of independence from any help, physical or verbal, however minor and for whatever reason.

European quality of life-5 dimensions with 5 level (EQ-5D-5L): The descriptive system of the EQ-5D comprises five dimensions: mobility (MO), self-care (SC), usual activities (UA), pain/discomfort (PD), and anxiety/depression (AD); each dimension is described at five levels, corresponding roughly to no, slight, moderate, severe, and extreme problems.

European quality of life-5 dimensions with 5 level (EQ-5D-5L): The descriptive system of the EQ-5D comprises five dimensions: mobility (MO), self-care (SC), usual activities (UA), pain/discomfort (PD), and anxiety/depression (AD); each dimension is described at five levels, corresponding roughly to no, slight, moderate, severe, and extreme problems.

The Lawton instrumental activities of daily living scale (IADL): IADL is an appropriate instrument to assess independent living skills. The instrument is most useful for identifying how a person is functioning at the present time, and to identify improvement or deterioration over time. There are eight domains of function measured with the Lawton IADL scale. Women are scored on all 8 areas of function; historically, for men, the areas of food preparation, housekeeping, laundering are excluded. Clients are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women, and 0 through 5 for men.

The Lawton instrumental activities of daily living scale (IADL): IADL is an appropriate instrument to assess independent living skills. The instrument is most useful for identifying how a person is functioning at the present time, and to identify improvement or deterioration over time. There are eight domains of function measured with the Lawton IADL scale. Women are scored on all 8 areas of function; historically, for men, the areas of food preparation, housekeeping, laundering are excluded. Clients are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women, and 0 through 5 for men.

Physical Self-Maintenance Scale (PSMS): To assess functional abilities in elderly patients. The format the PSMS is first a six item based on the ADL and then eight-items based on the IADL scale. A 5-point scale for responses ranges from total independence to total dependence.

Physical Self-Maintenance Scale (PSMS): To assess functional abilities in elderly patients. The format the PSMS is first a six item based on the ADL and then eight-items based on the IADL scale. A 5-point scale for responses ranges from total independence to total dependence.

The short-form 36 item health survey (SF-36): The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.

The short-form 36 item health survey (SF-36): The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.

Social Support Rating Scale (SSRS): SSRS developed by Xiao was utilized to measure social support. The 10-item scale consists of 3 dimensions including objective support, subjective support and availability. Higher scores indicate higher levels of social support. The scale has presented impressive validity and reliability in Chinese population.

Social Support Rating Scale (SSRS): SSRS developed by Xiao was utilized to measure social support. The 10-item scale consists of 3 dimensions including objective support, subjective support and availability. Higher scores indicate higher levels of social support. The scale has presented impressive validity and reliability in Chinese population.

Pittsburgh sleep quality index (PSQI): Sleep quality was assessed using the Chinese version of the PSQI, which is composed of 19 items classified into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction during the past month. Each component is weighted from 0 to 3, generating one global score ranging from 0 to 21. The higher score the poorer sleep quality.

Pittsburgh sleep quality index (PSQI): Sleep quality was assessed using the Chinese version of the PSQI, which is composed of 19 items classified into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction during the past month. Each component is weighted from 0 to 3, generating one global score ranging from 0 to 21. The higher score the poorer sleep quality.

Geriatric Depression Scale (GDS-15): The short form including 15 items. Items represent characteristics of depression in the elderly in the affective (e.g., sadness, apathy, crying) and cognitive domains (e.g., thoughts of hopelessness, helplessness, guilt, worthlessness. Higher GDS scores are indicative of more severe depression.

Geriatric Depression Scale (GDS-15): The short form including 15 items. Items represent characteristics of depression in the elderly in the affective (e.g., sadness, apathy, crying) and cognitive domains (e.g., thoughts of hopelessness, helplessness, guilt, worthlessness. Higher GDS scores are indicative of more severe depression.

The MoCA is a 1-page test that measures several cognitive domains (visual perception, executive skills, language, attention, memory and orientation). The MoCA score ranges from 0 to 30 (30 = best) and was chosen for its relatively high sensitivity for mild cognitive impairment.

The MoCA is a 1-page test that measures several cognitive domains (visual perception, executive skills, language, attention, memory and orientation). The MoCA score ranges from 0 to 30 (30 = best) and was chosen for its relatively high sensitivity for mild cognitive impairment.

For the T1 MRI images, we first performed quality control using CAT12 to exclude subjects with quality scores lower than "B". Next, we used the recon-all command of FreeSurfer 6.0.0 for brain extraction, tissue segmentation, cortical reconstruction, and brain region labeling for each subject's brain images. We extracted the thickness, surface area, volume for cortical structures, and volume of subcortical structures in different brain regions based on the DK+Aseg parcellation template. Finally, the brain images of each subject were nonlinearly aligned to the MNI152 template using ANTs alignment toolkit for subsequent analysis of BOLD fMRI and DWI images.

For the T1 MRI images, we first performed quality control using CAT12 to exclude subjects with quality scores lower than "B". Next, we used the recon-all command of FreeSurfer 6.0.0 for brain extraction, tissue segmentation, cortical reconstruction, and brain region labeling for each subject's brain images. We extracted the thickness, surface area, volume for cortical structures, and volume of subcortical structures in different brain regions based on the DK+Aseg parcellation template. Finally, the brain images of each subject were nonlinearly aligned to the MNI152 template using ANTs alignment toolkit for subsequent analysis of BOLD fMRI and DWI images.

We used the alignment results of the T1-weighted image of each subject to transform the resting-state images into MNI152 space , and calculated the functional connectivity between all brain regions, as well as the ALFF, fALFF mean values for each brain region according to the DK+Aseg partitioning template.

We used the alignment results of the T1-weighted image of each subject to transform the resting-state images into MNI152 space , and calculated the functional connectivity between all brain regions, as well as the ALFF, fALFF mean values for each brain region according to the DK+Aseg partitioning template.

For DWI images, we mainly used the FSL toolkit for processing. First, the b0 images of each subject were aligned with the T1 images, followed by eddy correction and head motion correction, and detection and replacement of outliers. Next, we used the DK+Aseg parcellation template for probabilistic fiber tracking of DWI images for each subject, and finally generated a probabilistic white matter connectivity matrix for each brain region for subsequent extraction of graph theoretical metrics.

For DWI images, we mainly used the FSL toolkit for processing. First, the b0 images of each subject were aligned with the T1 images, followed by eddy correction and head motion correction, and detection and replacement of outliers. Next, we used the DK+Aseg parcellation template for probabilistic fiber tracking of DWI images for each subject, and finally generated a probabilistic white matter connectivity matrix for each brain region for subsequent extraction of graph theoretical metrics.