Methodology

9.1 Ethics & CTRI:

The ethics approval was obtained from Institutional Ethics Committee of Ahmedabad
Institute of Medical Sciences with ethics approval number AIMS/2016/75 (Annexure I) and
from Sharda College of Physiotherapy with ethics approval number SCP/2017/001
(Annexure II).

The study has been registered with Clinical Trial Registry of India with registration number
CTRI/2018/01/011090. (Annexure III)

The study was divided into two phase over a period of 3 years.

9.2 Phase I Methodology:

Population: Older adults with or without cognitive impairments

Source of data: Old age homes, Clubs operating for older adults, gardens and community
dwelling older adults

Study design: Observational correlational study

Sampling design: Convenience sampling

Sample size: 150 subjects

Sample size was calculated using the formula n=4pq/E2, where p=0.05, q=0.95 and
E=allowable error of 10% of the p.

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 Inclusion Criteria:

 Both males and females between 60 to 75 years of age

 With or without cognitive impairments
 Willing to participate in the study
 Readiness to exercise – checked by PARQ (Annexure IV)

Exclusion criteria:

 Impaired dexterity of upper limbs

 Having visual impairment where eye site cannot be corrected to normal level
 Having hearing impairment where audition cannot be corrected to normal level
 Unstable medical condition

Outcome measures:

Addenbrook’s Cognitive Examination – III (ACE – III)

Six minute walk test (6MWT)

Quality of Life – Alzheimer’s disease (QoL-AD)

9.3 Material used for the study:

 Pen
 Pencil
 Paper
 Measure tape
 Cones
 Chair
 Pulse Oxy meter
 Stop Watch
 Computer
 Mobile phone

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9.4 Procedure:

9.4.1 Addenbrook’s Cognitive Examination – III (Annexure VI)

The authors of ACE-III were approached for the permission of translation of it to Gujarati.
On agreement, the authors provided Australian English Version of ACE-III and its scoring
guidelines; the same was translated to Gujarati and culturally adapted for Gujarati population.

ACE III has total five components, attention, memory, fluency, language and visuospatial
ability. All these components were studied in detail. Then, the Gujarati translation was
carried out by two independent translators. These translators were native Gujarati speakers
and were fluent in English. As per the guidelines by Rose Martini and colleagues71the
translators were chosen who had different backgrounds. Out of the two translators, one
translator was familiar with the concepts being translated whereas the other was not. The first
translator had a background of physiotherapy and healthcare. The other translator had a
background of literature and education. After obtaining the translations from both the
translators, the copies were amalgamated as first translation. The first translation was
reviewed and the report was prepared. The changes required were documented which
included change of certain terminologies and changes in different domains.

Attention domain required no changes.

The fluency domain has a task of saying as many words as possible from given letter. In
English the letter given is “C”. For Gujarati version the same letter was translated with had a
pronunciation of “C”. The English examples of words staring from “C” like cat, cry and
clock were modified to different Gujarati words which had a pronunciation starting from
letter “C”.

The memory domain required repeating and recalling an English name and address in English
version. For Gujarati version, the name and address were changed to more relevant relatable
name and address. Questions for general knowledge were also changed to more relevant
questions for Gujarati population.

The language domain has total six tasks. The first, “Pencil and Paper Task” and second one,
the “Repeat the words” were retained as they were for Gujarati version. “Repeat the
proverbs” task had English proverbs, which were changed to more relevant Gujarati proverbs.

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“Name the picture” task had 12 pictures to be named and four questions to be answered based
on the pictures given. Here, the picture of kangaroo was changed to cow, penguin to peacock,
anchor to hammer, harp to tabla, barrel to bucket, crown to bicycle, and accordion to flute.
Rest of the pictures were retained as they were in the original English version. The questions
were changed based on the pictures and as per the requirement. “Read the words” task had
English words which were relatively difficult to pronounce. These words were changed to
Gujarati words which had different meaning but similar level of difficulty.

There were no changes required in visuospatial ability task except “identifying the letters”.
The English version had alphabets which were changed to Gujarati alphabets having same
pronunciation as English alphabets.

After making the required changes, the first translated copy was obtained and then it was
translated back to English by an independent non-professional translator. This translator was
a bilingual physiotherapist but not practicing in geriatric, neurology or neuropsychiatry field.
In order to avoid information bias, the translator was not made aware or informed about the
concept of the translation. This might also helped to provoke unanticipated meanings of the
items in the tool. This translated copy was compared with original English version and the
differences between the two were documented. Based on these differences, there were further
modifications in first translated copy.

The process of forward –backward – forward translation method72continued till the

acceptable second copy of Gujarati translation was obtained.

Validity:

For the face Validity73, seven professionals working in neurological medicine and neuro
rehabilitation field having mean experience of 12 years examined the translated second copy
of the instrument. They categorized each item as accepted, accepted with modification or
rejected. The report was prepared and modifications were made till the expert panel of seven
professionals reached common consensus. None of the item was categorized as rejected. Thus
third copy of the translation was obtained which was tested for content validity.

Content validity was tested by Haccoun’s75 and Rose Martini’s 73 single group technique. The
technique requires bilingual individuals. Ten bilingual older adults of age between 60 to 75
years were selected. Their native language was Gujarati but they were fluent with English.
Their cognitive assessment was taken with both English and Gujarati ACE-III randomly.
They were asked if they could understand all components and concept of the scale in both the

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language, whether they felt the need to replace any component or if there was any instruction
which could not convey the concept properly. Accordingly a report was written and no
corrections were required.

Final Version:

After all the amendments, the final Gujarati translation was prepared and it was meticulously
proof read for any inaccuracies. The final version obtained was then submitted to the
developers of ACE-III.

Figure 1: Method of translation of ACE-III

The developers and authors of ACE-III were approached with the proposal to translate and
culturally adapt ACE-III to Gujarati

ACE-III, its components and scoring guidelines were studied in detail

Translation of ACE-III to Gujarati by two independent translators

First translation copy was reconciled from two translated copies and report was prepared for
the required changes

Translation of the first copy back to English by independent non –professional translator

Documentation of differences between the translated copy and original English version are
documented and process of forward – backward- forward translation continued till acceptable
second Gujarati copy obtained

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 Figure 2: ACE-III validity

Second translated copy handed over to experts

Each item was analysed as – accepted, accepted with modification or rejected

Report of items requiring modification was prepared and the items were modified till all the
items reached common consensus.

Third copy of Gujarati translation was prepared and was tested for content validity

10 bilingual older adults both males and females between the age 60 to 75 years were
assessed for level of cognition with both Gujarati and English ACE –III in random order with
interview method

Report was prepared and minor modifications were made as per the suggestions by the
participants and the data obtained was statistically analysed

Final Gujarati version of ACE-III and its scoring guidelines was submitted to the authors

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Gujarati version of ACE – III was used to examine the level of cognition. (Annexure VII).

ACE – III includes total five cognitive domains: attention, memory, verbal fluency, language
and visuospatial abilities. It has total score of 100 and more score indicates better cognition.
Attention has a total score of 18, memory 26, fluency 14, language 26, and visuospatial
ability 16. It took 15 to 20 minutes to administer the test. And scoring took five more
minutes.74

Training to administer ACE-III was undertaken. The online training is provided by National
Health Services Scotland in collaboration with University of Glasgow. The training includes
the video explanation of ACE – III and its components, examination of Cognition with ACE
– III on different geriatric population, how to score ACE – III and how to calculate the score.
At the end of the training, there is an online test, undergoing the entire tutorial and test the
training is considered complete.(Annexure VIII)

9.4.2 Six Minute Walk Test:

All the participants were explained the procedure in detail and were given a practice for the
same. Following practice session, the test was conducted. The test was carried out indoors,
either in the hall or in unobstructed corridor. The length of the walkway was 100 m and the
test was carried out as per the guidelines of American Thoracic Society.70

Before beginning the test, the resting heart rate was measured using pulse oxymeter.
Individual’s weight and height was measured. The individuals were instructed to cover as
much distance as possible. During the test no verbal encouragement was given. If the
individual wanted to stop for rest during the test, he/she was allowed to do so, but the
counting of the minutes continued even when the individual was resting.70

At the end of six minutes, the individual was asked to stop where he/she was. Total covered
distance was counted. Also, immediate heart rate was checked using pulse oxymeter. The
Aerobic Capacity was calculated using the equation

Peak VO2 (ml / kg /min) = 4.948+0.023 x Mean 6 MWD (meters).70

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Figure 3 shows an individual performing 6MWT.

Figure 3: 6MWT

9.4.3. Quality of Life – Alzheimer’s disease Questionnaire (Annexure IX)

Quality of Life of subjects was assessed by Quality of Life Alzheimer’s disease (QoL-AD)
questionnaire. It assesses quality of life including physical health, energy, mood, memory,
ability to do chores around the house, ability to do things for fun, self as a whole etc. The
total score of Qol- AD is 52. There are total 13 items, each item is rated as poor, fair, good or
excellent with poor being 1 and excellent as 4.28

Total 150 older adults, aged between 60 to 75 years were screened for the study according to
the inclusion/exclusion criteria. 129 participants met the criteria and were recruited. Informed
written consent was obtained from all the participants. Subjects were assessed for aerobic
capacity using 6MWT. Cognitive levels were assessed using ACE-III. Quality of life was
assessed using QoL-AD.

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 Figure 4: STROBE report of Phase I.

150 Participants screened for eligibility

21 participants excluded –
7 – not willing to participate
10 – either vision, hearing could
not be corrected to normal level
4 – not able to write

Included in the study =129

Assessed for ACE – III, 6MWT and QoL-AD

The obtained data was then analysed using Microsoft Excel and SPSS version 16.

9.5 Phase II Methodology:

Population: Older adults

Source of data: Old age homes, Clubs operating for older adults and community dwelling
older adults

Study design: Experimental study

Study subjects: 32 subjects with 16 subjects in each group

Sample size: N= 2(𝜎|∆)2[Zα+Z1-β]2

Where N is sample size per group, σ is Standard Deviation, ∆ is critical difference, Zα is level
of significance and Z1-β is power.

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Expected SD in each group was 0.67, level of significance was kept at 0.05, critical
difference 1.23 and power of 99%, the sample size came to 12. Considering the dropout
scenario, the sample size for the current study was kept as 16 per group.

Allocation: Random allocation

Treatment duration: Eight weeks

Inclusion Criteria:

 Males and Females - Age group: 60 to 75 years

 Individuals having smart phones and are comfortable with its use
 Mild cognitive impairment diagnosed with ACE – III (score between 82 to 88)
 Eligible for aerobic training as per Physical activity readiness Questionnaire

Exclusion criteria:

 Any neurological condition causing cognitive impairment

 Impaired dexterity of upper limbs
 Having visual impairment where eye site cannot be corrected to normal level
 Having hearing impairment where audition cannot be corrected to normal level

Outcome measures:

Six minute walk test (6MWT)

Addenbrook’s Cognitive Examination – III (ACE-III)

Neuro Cognitive Performance Test (NCPT)

Quality of Life – Alzheimer’s disease (QoL-AD)

Total 32 subjects aged 60 to 75 years participated in the study. Informed written consent was
obtained from all the participants. The same procedures were followed as mentioned in Phase
I of the study to assess ACE-III, 6MWT and QoL-AD. In addition, the participants were
assessed with NCPT.

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Neuro Cognitive Performance Test:

Cognition was also measured with Neuro Cognitive Performance Test (NCPT). We used
Object recognition, and delayed object recognition, go- no go (speed test), trail making B,
scale balance (logic), and dual search (divided attention) tests as a part of NCPT. The tests
have acceptable levels of reliability and validity. It takes around 25 to 30 minutes to
complete.26 (Figure 3 and 4)

Permission to use Lumosity – a mobile app for cognitive training and NCPT was
obtained.(Annexure X)

After the assessment, the subjects were randomly divided to two groups. The randomization
order was generated using [Link]. Group one was assigned aerobic
exercise, whereas group two was assigned mobile application intervention. Both groups
underwent the intervention for period of eight weeks. Both groups had to undertake the
training for at least 30 minutes a day for five days per week. The flow chart is shown in
figure 5.

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 Fig 5: CONSORT Flow Diagram – Phase II

ENROLMENT
Assessed for eligibility (n=129)

Excluded (n= 95)

Not meeting inclusion criteria (n= 93)
Declined to participate (n=2)

Randomized (n= 32)

ALLOCATION
Allocated to intervention (n= 16) Allocated to intervention (n=16)
Received allocated intervention (n= 16) Received allocated intervention (n= 16)

FOLLOW-UP
Lost to follow-up (n= 0) Lost to follow-up (n=0)

Discontinued intervention (n= 0) Discontinued intervention (n= 0)

ANALYSIS
Analysed (n= 16) Analysed (n=16)

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 Figure 6: NCPT report of Object Recognition and Scale Balance.

Figure 7: NCPT report of Go – No Go Test, Dual Search, Trail Making B and Delayed
Object Recognition

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9. 6 Phase II Procedures

Group 1:

Individuals in this group underwent aerobic exercise training. The individuals were taught
thirty minutes of exercise which included warm up and cool down. Tailor made protocol was
used for all the individuals, which generally it included exercises like, spot marching, brisk
walking, star exercise, mini squatting, spot jogging, jumping jacks, stair climbing, static
cycling, chair aerobic workout, etc. The exercises were of moderate intensity, performed for
30 minutes, 5 days a week for eight weeks as per ACSM guidelines for older adults.75

The training was performed under the supervision of the therapist to make sure that the
exercises are performed correctly. The therapists providing aerobic training to the participants
were blinded about the study.

Figure 8, 9, 10 and 11 show the participants performing aerobic activities.

Figure 8: Warm up exercise

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Figure 9: Warm up exercise Figure:10 Jumping jacks

Figure :11 Spot marching

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Group 2:

The individuals in this group used mobile application Lumosity©. The applications provided
interactive games for various aspects of cognition like, planning, information processing,
divided attention, spatial orientation, working memory, selective attention, task switching,
logical reasoning, vocabulary, numerical estimation, numerical calculations, etc.

The application provided a reminder to the user at a set time every day. The individuals were
given daily targets by app. In addition to this, the application saved information as how many
days in a week an individual has played games and what varieties of games are being played.
This provided information about the compliance of the participants. Weekly follow up of
individuals were done by the therapist over phone if they are facing any difficulty while
playing. If individual encountered an issue, the therapist visited the individual and the query
was sorted out.

Figure 12 shows the number of days the participant completed the given set of challenge. It
also gives information about the compliance, that for how many consecutive days an
individual has played Lumosity.

Figure: 12 – Workout streak and compliance

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Figure 13 shows a game “Speed Pack” which works on speed. It also enhances the ability to
manipulate or imagine the interaction of objects in mind. The game requires an individual to
quickly decide the place for an object which is placed outside the bag. The object has to be
placed in such a way so that after closing the bag two fold it will not overlap any other
objects already present in the bag.

Figure: 13 Speed Pack

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Figure 14 and 15 shows the game “Lost in Migration”. It works on selective attention. It
enhances the ability to focus on relevant information while ignoring irrelevant distractions.
The game has group of birds on the screen. And an individual must swipe in the direction of
the centre bird ignoring the directions of the other birds on the screen.

Figure 14: Lost in Migration Figure 15: Lost in Migration

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Figure 16 and 17 shows the game “Ebb and Flow” for flexibility. It works on adapting to
changing circumstances, switching from one goal to another. The game requires an individual
to quickly react to the changes on the screen. It has two set of leaves which floats in certain
direction. On seeing green coloured leaves, individual will have to swipe in the direction to
which the leaves are pointing. On seeing orange coloured leaves, the swipe has to be in
direction in which the leaves are moving.

Figure 16 and 17: Ebb and Flow

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Figure 18 shows the game “Train of Thought”. It works on divided attention. It allows
individual to process multiple streams of information. The game has various coloured engines
which have to be directed to matching coloured dome by simultaneously adjusting the tracks.

Figure 18: Train of thought

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Figure 19 is of game “Tidal Treasure”. It is a memory game which emphasises on temporary
storage and manipulation of information. In this game, there are numerous objects presented
on the screen. Each time a new object has to be picked without repeating the previously
selected object.

Figure 19: Tidal Treasure

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Figure 20 is the game of “Memory Matrix” which helps an individual to get trained in
memory which is involved in tracking location and position within an environment. Here, the
player has to tap and create the same pattern of the tile which was shown to him/her earlier.
After every trial the complexity of the pattern would increase and the number of the tile will
increase too.

Figure 20: Memory Matrix

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Figure 21 shows the game “Trouble Brewing”. It helps to train on simultaneously response to
multiple tasks or task demands. Here the person asked to prepare the beverages as per the
orders. And as the previous orders get ready, the new orders are ready to be prepared.

Figure 21: Trouble brewing

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Figure 22 shows the game “Star Search” which enhances the ability to focus on relevant
information while ignoring irrelevant distractions. Here, the person has to identify an object
which differs from the other objects on the screen.

Figure 22: Star Search

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Figure 23 has a game “Disillusion” which works on the process of adapting to changing
circumstances, switching from one goal to another. If an object is displayed vertical, it should
be placed with an object of same color. If object appears horizontal, it should be placed with
an object of same shape.

Figure 23: Disillusion

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Figure 24 has a game “Masterpiece” which trains Spatial reasoning. Spatial reasoning is the
ability to visualize spatial relationships and analyse them to draw conclusions. It has an art
piece with some broken pieces which has to be fixed correctly.

Figure 24: Master piece

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Figure 25 and 26 are of game “Fuse Clues”, which helps to combine multiple cognitive
processes to recognize patterns, draw conclusions, and make decisions. It has series of
numbers which has to be arranged in given pattern.

Figure 25: Fuse clues Figure 26: Fuse Clues

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Figure 27 “Pet Detective” helps the person to train the process of planning, evaluating
options then choosing the best course of action. This game requires an individual to plan in
advance and choose the path which will make all pets reach their respective homes with
minimum steps.

Figure 27: Pet Detective

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Figure 28 “Rain Drops” shows the game for simple arithmetic operations. There is sequential
display of arithmetic problems, it has to be solved quickly in order to continue playing game.

Figure 28: Rain drops

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Figure 29 and 30 “Chalkboard Challenge” trains on ability to approximate the numerical
relationships quickly or with incomplete information. It has numerals displayed and the
individual has to judge if one value is greater than the other or both the values are equal. And
individual has to respond quickly to earn more points.

Figure 29: Chalk board challenge Figure 30: Chalkboard challenge

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Figure 31 and 32 “Spatial Speed Match” works on initial identification and analysis of
incoming sensory input. There are three dots on the screen and at each time a different dot
will be highlighted. A player has to decide if the dot currently highlighted matches the
position of the dot highlighted in the previous presentation.

Figure 31: Speed match Figure 32: Speed match

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Figure 33 shows the game “Color Match”, it works on ability to suppress impulsive response
that interferes with accomplishing goals. There are two different slides displayed on the
screen. One with the meaning and other one with text colour. A player has to decide if the
text colour matches the meaning.

Figure 33: Color Match

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At the end of eight weeks, individuals from both the groups underwent an assessment with
ACE-III, six minute walk test, NCPT and QoL-AD. Completion of 80% of the protocol was
considered as compliance, to be included in the post treatment analysis.

Statistical Analysis:

The obtained data was then analysed using Microsoft Excel and SPSS version [Link] data
was analysed for the test of normality with K-S Test. For Phase I, ACE- III and QoL-AD
were not normally distributed, and Aerobic capacity was normally distributed. The non-
parametric test Spearman Correlation Coefficient was carried out for the correlation of the
data. For Phase II, the data of ACE – III and Trail B was not found to be normally
distributed; hence non parametric tests were carried out. Mann Whitney U test was used to
find out the difference between Exercise group and Mobile application group for the ACE –
III score, and Trail B. Wilcoxon Signed Ranks test was used to find out the difference of
scores Pre and Post intervention within the group. p value of less than 0.05 was considered
significant. The data of aerobic capacity, QoL-AD and Immediate Recall, Dual Search, Go –
No Go, Scale Balance and Delayed recall was found to be normally distributed; hence
parametric tests were carried out. Independent sample t test was used to find out the
difference between the groups and paired t test was used to find the difference within the
group. p value of less than 0.05 was considered significant.

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