Effectiveness of Nurse-led Clinics Training Program on Mild Cognitive Impairment Patients: a Randomized Controlled Trial Protocol
Phase: NA
Conditions: Mild Cognitive Impairment
Sponsor: Xuanwu Hospital, Beijing

Study protocol and Statistical Analysis Plan
Title:Effectiveness
of
nurse-led
clinics
training
program
on
mild
cognitive
impairment
patients: a randomized controlled trial protocol
NCT number:2021029
Date of the document:2024-01-03

Study protocol
Abstract
Introduction: Globally, nurse-led clinics(NLCs) have been developed to serve and
follow up on patients who have just been discharged from the hospital. NLCs
cognitive training program as a potentially effective and promising treatment for MCI
patients.
Methods: The study is a single-blind, randomized-controlled trial. Eligible patients
need to be diagnosed as MCI. Participants will be randomized into either a NLCs
training group or a home-based training group. Both groups will undergo total 72hour
across 12 months. The outcome measures will be assessed at baseline, at the 6 months
and 12 months during the intervention. The primary outcome is global cognitive
function, assessed by the 30-item the Mini-Mental State Examination (MMSE), and
the secondary outcomes include changes in other neuropsychological assessments and
in result of resting electroencephalography (EEG) .
Results: The trial is currently ongoing, and it is anticipated that recruitment will be
completed in June 2025.
Discussion: This trial will evaluate the efficacy and safety of NLCs cognitive training
in patients with MCI, and further explore the potential mechanisms by analyzing teh
results of neuropsychological assessments and EEG.
Trial registration:
Keywords: mild cognitive impairment, nurse-led clinics, computerized cognitive
training, randomized controlled clinical trial
1 Introduction
Cognitive impairment that is a syndrome with persistent cognitive impairment
occurs on a continuum from mild, moderate, to severe states, which is manifested as
one or more impairments in cognitive domains.1 There is a high prevalence of mild
cognitive impairment (MCI) in China. Among adults aged 60 and above, there are
about 38.77 million MCI patients with a prevalence rate as high as 15.5%.2 In
addition, among nervous system diseases, 22.8% patients with Parkinson's disease and
34%~65% patients with multiple sclerosis also have cognitive impairment.3,4 The
provision of social care and the hours of unpaid care by families for patients who are
living with cognitive impairment currently costs amount to £15.7 (US $21.6) billion
and £13.9 (US $19.2) billion a year respectively.5 Given the magnitude of the problem
in terms of individuals or family affected and the costs associated with cognitive
impairment, the prevention and treatment of cognitive impairment is currently a
public health priority at the center of the global action plan (2017–2025), requiring
new solutions to support patients and families in managing disabilities related to the
disease.6
In this context, the need to promptly intervene with cognitive training on residual
capabilities is well known. Previous studies have shown computerized cognitive
training (CCT) interventions could improve global cognitive function in patients with

MCI.7 At the same time, cognitive training can significantly improve the overall
cognitive function of patients regardless of short-term (≤10 weeks), medium-term
(10~20 weeks) or long-term ( ≥20 weeks) intervention.8 Furthermore, giving
intensive training after the normal training dose maybe get preferable cognitive
function improvement and effect maintenance.9
The increasing prevalence of MCI and importance of CCT have led to a growing
demand for cognitive training services in an outpatient setting. It is likely to be a
critical point of continuous, sufficient dose and high quality cognitive training in the
effect of CCT.10 Hence, remote guidance and detection by medical staff are important
for patients to cognitive training to meet the individual needs.11 Globally, nurse-led
clinics(NLCs) have been developed to serve and follow up on patients who have just
been discharged from the hospital. NLCs are defined as clinical practice facilities
where nurses have their own formalized and structured standard to address healthcare
needs of patients and their families.12 The clinics are run by advanced practicing
nurses (APNs) who can monitor and support MCI to persist in cognitive training for a
long time after discharge. In each consultation, the APNs also equip their families
with the knowledge and caregiving skills to deal independently with the numerous
challenges faced by their loved ones, thereby reducing the feeling of caregiving
burden. The novelty of nurse-led clinics in cognitive training, randomized controlled
trials demonstrating the effectiveness of the solution is still scarce.
This trail is the first study to test the efficacy of nurse-led clinics cognitive
training on MCI patients using a single-blind, randomized controlled trial design. We
hypothesize that nurse-led clinics cognitive training can (a)decelerate or ameliorate
cognitive decline, (b)ameliorate anxiety and depressive symptoms, (c)increase the
quality of life for both patients and family members, (d)improve the ability of daily
life, (e)reduce the incidence of agitation.
2 Methods
2.1 Study design
This single-center, single-blind trial. All participants will be recruited from
Xuanwu Hospital, Capital Medical University, Beijing. This study will be reported in
accordance with both the CONsolidated Standards of Reporting Trials (CONSORT)
statement and the CONSORT statement for nonpharmacological interventions.
The participants will be randomized into either a NLCs training group or a
home-based training group. Both groups will undergo 72, 1-hour sessions of NLCs
training or 144, 30-minute sessions of home-based training across 12 months. The
outcomes will be assessed at baseline, at 6-month and 12-month follow-up. The
outcomes will include multiple neuropsychological assessments to examine the effect
of NLCs training on cognitive functions, resting-state EEG to measure brain
connectivity and neural activity.
2.2 Participants

Patients with MCI will be recruited according to the following inclusion and
exclusion criteria.
2.2.1 Inclusion criteria
1. Subjects with informed consent;
2. Literate Han Chinese, above the age of 18;
3. At least 6 years of education;
4. Neither normal nor demented according to the criteria of the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, with a Clinical Dementia
Rating(CDR) ≥0.5 on at least one domain and a global score ≤0.5; a Mini-Menta State
Examination score ≥20 (primary school), or ≥24 (junior school or above).13
5. having normal vision and hearing with/without corrective devices.
2.2.2 Exclusion criteria
1. Severe aphasia, physical disabilities, or any other factor that might preclude
completion of neuropsychological testing.
2. Clinically significant gastrointestinal, renal, hepatic, respiratory, infectious,
endocrine, or cardiovascular system disease; cancer; alcoholism; drug addiction.
3. Illnesses affecting mobility or are unable to accept assessments or interventions that
are required in this study.
Randomization
Participants will be randomly allocated to either the intervention group or the
control group in a ratio of 1:1. After participants have given their informed consent,
randomization will be performed by an independent statistician who is blinded to the
patient interventions using IBM SPSS Statistics Software following the sequence:
Data/select cases/random sample of cases/exact 1 case of the 2 total cases. Afterwards,
the sealed randomization codes and intervention number are sent out to each center.
Blinding
Radiologists, statisticians, and neuropsychologists who measure the outcomes
will be blinded to the randomization status. Blinding will also be maintained for data
management, outcome assessment, and data analysis. Participants and therapists
cannot be blinded to the intervention they receive or provide.
Intervention
CCT that is a multi-domain adaptive training program is used in this trial.
Training paradigms include processing speed, attention, long-term memory, working
memory, flexibility, calculation, and problem solving. To enable adaptive training,
each task was designed with several difficulty levels. At the beginning, assignment
tasks from these domains will be similar across participants. On each training day,
five tasks (2 min per task, each three times, in total 30 min per day) will be assigned.
Within each task, high accuracy (>80 %) is required to upgrade. The training is thus
also adaptive at participant level, with a similar setup but personalized progress across

participants.
Cognitive training in NLCs, CCT was given twice a week during 1-6 months and
once a week during 7-12 month in nursing clinic. There is 60 minutes at a time. All
the patients were capable of performing the training under the guidance of APNs. At
the same time, according to the caregivers' feedback, APNs will give them the desired
care guidance.
Cognitive training in home, CCT was given four times a week during 1-6 months
and twice a week during 7-12 month in nursing clinic. There is 30 minutes at a time.
Nurses teach patients to acquire and carry out CCT at home during hospitalization.
Nurses set the daily reminder function at 9:00am through training system. The data
results of each training will be automatically stored in the personal information
database in the cloud. And, a training report will be generated, including training
difficulty, training results and training time. Nurses can examine patients' training
through the cloud.
Cognitive training in tradition, the Home Cognitive Training Manual for
Alzheimer's Disease compiled by our research team was distributed. And, the patients
and their families were given detailed health education on the definition, clinical
manifestations, drug and non-drug treatment, home nursing, the significance of
cognitive training and the methods of cognitive training. Meanwhile, we established
connection with patients for later follow-up.
2.5 Outcome measures
2.5.1 Neuropsychological assessments
The intervention will be assessed by the Mini-Mental State Examination (MMSE)
and the Montreal Cognitive Assessment (MoCA), in which scores range from 0 to 30,
with higher scores representing better general cognitive performance.14,15
The World Health Organization-University of California-Los Angeles Auditory
Verbal Learning Test (WHO-UCLA AVLT) which scores range from 0 to 45 will be
used to assess memory function, with a higher value representing a better outcome.16
The Boston Naming Test (BNT) will be used to assess language performance,
specifically visual naming ability.17
Instrumental activities of daily living(IADL) and barthel index is defined as
being whether able to complete activity ability.18,19
Hamilton Anxiety rating scale(HARS), the geriatric depression scale(GDS), the
Cohen–Mansfield Agitation Inventory (CMAI) and neuropsychiatric Inventory(NPI)
will be used to measure neuropsychiatric symptoms.20-23
Zarit caregiver burden interview (ZBI) will be used to assess the burden of
caregivers.24
2.5.2 Resting EEG
EEG was acquired using a 32-conductor Ag-AgCl electrode cap and amplifier
(BioSemi, Amsterdam, Netherlands) with a 2048-Hz sampling rate. To reduce
interference during signal acquisition, we ensured that the electrode resistance was<5
kΩ. During data collection, the participants were seated in a comfortable chair,

relaxed, refrained from speech or voluntary movements, and kept their eyes closed.
The eyes-closed state was recorded for 5 min, and the data were stored on a computer
for offline analysis.
2.5.3 Primary outcome
The primary outcome measure is the score change in MMSE from baseline to the
end of the intervention.
2.5.4 Secondary outcome
The secondary outcomes for neuropsychological assessments include the score
change from baseline to the 6-month and 12-month after intervention in other scales.
The EEG results also dose.
2.6 Data collection
Inclusion and exclusion criteria will be assessed at screening. After written
informed consent is acquired, the following data will be collected: demographic data
(gender, age, education, and occupation); medical history; concomitant medications;
and findings from a complete physical examination and neurological examination.
Then, neuropsychological assessments, and EEG will be carried out. The follow-up
assessments will be scheduled at 6-month and 12-month after intervention. The study
schedule of the trial is shown in Table 1. The study flowchart is presented in Figure 1.
Table 1 Schedule of the trial
Study period
Time point
screening
baseline
6-month intervention
12-month intervention
Eligibility screen
×
Informed consent
×
Randomization
×
Demographic data
×
CDR
×
Assessments
MMSE
×
×
×
×
MoCA
×
×
×
WHO-UCLAAVLT
×
×
×
BNT
×
×
×
IADL
×
×
×
BI
×
×
×
HARS
×
×
×
GDS
×
×
×
CMAI
×
×
×
NPI
×
×
×
ZBI
×
×
×
EEG
×
×
×

FIGURE 1 The flowchart of this trial
2.7 Data monitoring
The study will comply with the Declaration of Helsinki. The neuropsychological
functions of all participants will be evaluated by the same trained neuropsychologists.
EEG data will be acquired according to the same parameters and using the same
scanner.
2.8 Sample size
There are no published randomized controlled trials on NLCs cognitive training
or home-based cognitive training in MCI patients. In our preliminary experiments, the
intervention resulted in improvement in MMSE scores (mean: 0.5 vs 0.04). According
to these data, to obtain a statistical power of 90% with a significance level of 5%, the
sample size needs to be 26 for each group. To allow for a maximum dropout rate of
20%, the sample size is set to 32 participants in each group.
2.9 Statistical analysis
All data will be analyzed according to intent-to-treat principles. Continuous data
were reported as means ± standard deviation and were analyzed using one-way
ANOVA or Kruskal-Wallis tests as appropriate. Categorical data were presented as
frequency and percentages and were analyzed using the chi-squared test. A
repeated-measures ANOVA was performed for 3-time points to evaluate the effect of
group factors, time factors, and the interaction between time×group on the outcomes
variables. A simple effect test was used to examine the difference among groups
within each time point and between the 3-time points within each group when the
interactions of time×group were significant. All statistical tests were two-sided, and
statistical significance was considered at p <0.05.
3 Discussion
The aims behind the introduction of nurse clinics were to contain costs and to
better integrate the pathway of care from the acute to the rehabilitative phase,

particularly for shortened hospital stays. In the Irish, nurse clinics were introduced to
provide intermediate care to patients discharged from hospital, yet in need of support
to regain their maximum health.25 In Hong Kong, the aim behind the establishment of
nurse clinics was in line with the international trend, that is, to enhance continuity of
care and access to care and to contain costs.26 Recovery is often a protracted
experience for MCI patients, warranting continuous, comprehensive training to
manage cognitive training and support family members. Despite this great need, many
patients discharged from an inpatient unit have limited access to outpatient training or
comprehensive support. Thus, now more than ever, it is paramount to consider novel
approaches to supporting persons training. The idea that NCLs can be established to
balance out the rehabilitation technician deficit is not secret knowledge.The proposed
study responds to a great need for ongoing professional support and, if successful,
will provide evidence regarding an alternative pathway to organizing comprehensive
professional support for MCI training.
4 Conclusions
Nurse-led clinics cognitive training has the potential ability to enhance cognitive
functions in MCI patients. This single-blind, randomized-controlled trial will verify
these effects.
REFERENCES
1. Sanford
AM.
Mild
Cognitive
Impairment[J].
Clin
Geriatr
Med.
2017
Aug;33(3):325-337.
2. Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia
and mild cognitive impairment in adults aged 60 years or older in China: a
cross-sectional study[J]. Lancet Public Health, 2020, 5(12):e661-e671.
3. Wang Q, Zhang Z, Li L, et al. Assessment of cognitive impairment in patients with
Parkinson′s disease: prevalence and risk factors[J]. Clin Interv Aging, 2014,
9:275-281.
4. Benedict R, Amato MP, DeLuca J, et al. Cognitive impairment in multiple sclerosis:
clinical management, MRI, and therapeutic avenues[J]. Lancet Neurol, 2020,
19(10):860-871.
5. How Many People Have Dementia and What Is the Cost of Dementia Care?
Alzheimer's
Society.
2019.
URL:
https://www.
alzheimers.org.uk/about-us/policy-and-influencing/dementia-scale-impact-numbers.
6. World Health Organization. Global action plan on the public health response to
dementia 2017–2025. 2017; Geneva, Switzerland.
7. Li R, Geng J, Yang R, Ge Y, Hesketh T. Effectiveness of Computerized Cognitive
Training in Delaying Cognitive Function Decline in People With Mild Cognitive
Impairment: Systematic Review and Meta-analysis[J]. J Med Internet Res. 2022 Oct

27;24(10):e38624.
8. Wang YY, Yang L, Zhang J, et al. The effect of cognitive intervention on cognitive
function in older adults with Alzheimer′s disease: a systematic review and
meta-analysis[J].Neuropsychol Rev, 2022, 32(2):247-273.
9. Nguyen L, Murphy K, Andrews G. Immediate and long‑term efficacy of executive
functions cognitive training in older adults: a systematic review and meta‑analysis[J].
Psychol Bull, 2019, 145(7): 698‑733.
10. Kalbe E, Folkerts AK, Ophey A, et al. Enhancement of executive functions but
not memory by multidomain group cognitive training in patients with Parkinson′s
disease and mild cognitive impairment: a multicenter randomized controlled trial[J].
Parkinsons Dis, 2020, 2020:4068706.
11. Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary:
Mild cognitive impairment: Report of the Guideline Development, Dissemination,
and Implementation Subcommittee of the American Academy of Neurology[J].
Neurology. 2018 Jan 16;90(3):126-135.
12. Wong FK, Chung LC. Establishing a definition for a nurse-led clinic: structure,
process, and outcome[J]. J Adv Nurs. 2006 Feb;53(3):358-69.
13. Chang YL, Bondi MW, McEvoy LK, et al. Global clinical dementia rating of 0.5
in MCI masks variability related to level of function[J]. Neurology. 2011 Feb
15;76(7):652-9.
14. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method
for grading the cognitive state of patients for the clinician[J]. J Psychiatr Res.
1975;12:189-198.
15. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive
Assessment, MoCA: a brief screening tool for mild cognitive impairment[J]. J Am
Geriatr Soc. 2005;53:695-699.
16. Zhou A, Jia J. A screen for cognitive assessments for patients with vascular
cognitive
impairment
no
dementia[J].
Int
J
Geriatr
Psychiatry.
2009
Dec;24(12):1352-7.
17. Bezdicek O, Rosická AM, Mana J, et al. The 30-item and 15-item Boston naming
test Czech version: Item response analysis and normative values for healthy older
adults[J]. J Clin Exp Neuropsychol. 2021 Nov;43(9):890-905.
18. Graf C. The Lawton instrumental activities of daily living scale[J]. Am J Nurs.
2008 Apr;108(4):52-62; quiz 62-3.
19. Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthel Index for
stroke rehabilitation. J Clin Epidemiol. 1989;42(8):703-9.
20. Bruss GS, Gruenberg AM, Goldstein RD, et al. Hamilton Anxiety Rating Scale
Interview guide: joint interview and test-retest methods for interrater reliability[J].
Psychiatry Res. 1994 Aug;53(2):191-202.
21. Montorio I, Izal M. The Geriatric Depression Scale: a review of its development
and utility[J]. Int Psychogeriatr. 1996 Spring;8(1):103-12.
22. Kupeli N, Vickerstaff V, White N, et al. Psychometric evaluation of the
Cohen-Mansfield Agitation Inventory in an acute general hospital setting[J]. Int J
Geriatr Psychiatry. 2018 Jan;33(1):e158-e165.

23. Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory:
comprehensive assessment of psychopathology in dementia[J]. Neurology. 1994
Dec;44(12):2308-14.
24. Lu L, Wang L, Yang X, et al. Zarit Caregiver Burden Interview: development,
reliability and validity of the Chinese version[J]. Psychiatry Clin Neurosci. 2009
Dec;63(6):730-4.
25. Rosalim JP. Service Provision Study on the Implementation of Nurse-Led Clinic
in the Irish Judicial System[J]. J Correct Health Care. 2020 Jul;26(3):258-266.
26. Wiles R, Postle K, Steiner A, et al. Nurse-led intermediate care: an opportunity to
develop enhanced roles for nurses?[J] J Adv Nurs. 2001 Jun;34(6):813-21.