Prevalence, Trajectories and Prognostic Significance of Mild Behavioral Impairments in Pre-Dementia populations

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Prevalence, Trajectories and Prognostic Significance of Mild Behavioral Impairments in Pre-Dementia

populations

Vilde Marie Andersgaard Follum

Candidate number: 2225

Project thesis

University of Oslo 2021

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Table of contents

Abstract ... 4

1 Introduction ... 5

1.1 Dementia – a global health problem ... 5

1.2 Dementia criteria in ICD-10 and DSM-5 ... 5

1.2.1 ICD-10 ... 5

Table 1 ... 6

1.2.2 DSM-5 ... 6

Table 2 ... 7

1.3 Mild cognitive impairment ... 8

1.4 Clinical Dementia Rating ... 8

1.5 Neuropsychiatric symptoms in relation to dementia ... 8

1.6 Mild behavioral impairment ... 9

1.6.1 MBI and NPI-Q ... 9

1.6.2 Diagnostic criteria for MBI ... 9

Table 3 ... 10

1.6.3 The Mild Behavioral Impairment Checklist ... 11

1.7 Aim of the study ... 11

1.8 Previous reviews ... 11

2 Method ... 12

2.1 Search strategy and selection criteria ... 12

2.2 Inclusion criteria ... 13

Table 4 ... 13

2.3 Exclusion criteria ... 13

Table 5 ... 13

2.4 Search process ... 13

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2.5 Flow diagram ... 14

Figure 1 ... 14

3 Results ... 15

3.1 Articles included ... 15

Table 6 ... 15

2.7 Articles excluded after full-text reading ... 19

Table 7 ... 19

3.1 Review of the included articles ... 22

4 Discussion ... 24

5 Appendix ... 26

Appendix 1 – CDR Scoring table ... 26

Appendix 2 – Neuropsychiatric Inventory-Questionnaire ... 27

Appendix 3 – Mild Behavioral Impairment Checklist (MBI-C) ... 28

7 Bibliography ... 30

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Abstract

Introduction: Mild behavioral impairment (MBI) is a relatively new term in the fields of geriatrics and old age psychiatry, and knowledge and research are still limited. MBI is defined as a syndrome with psychiatric and behavioral symptoms without the diagnostic criteria for dementia being met.

Aim: The aim of this study is to summarize the present state of knowledge about MBI regarding prevalence, trajectories and prognostic significance for further development of cognition, activities of daily living, survival and risk of delirium.

Methods: Existing literature of MBI in PubMed and Web of Science was reviewed. Search terms included “mild behavioral impairment”, “dementia”, “neuropsychiatric symptoms”,

“aggression”, “agitation”, “psychosis”, “hallucinations”, “delusions”, “anxiety”, “irritable mood”, “lability”, “apathy”, “euphoria”, “disinhibition”, “depression”, “aberrant motor activities”, “sleep disturbance” and “eating disorder”.

Results: The reported prevalence of MBI varied among cognitively normal persons (10.0 – 27.6%) as well as among patients diagnosed with mild cognitive impairment (MCI) patients (14.2 – 85.3%). The most common domain affected by MBI among the MCI population was found to be impulse dyscontrol and decreased motivation. The caregiver burden was higher for the MBI patients compared to those not meeting the MBI criteria. MBI is seen slightly more often in men than in women. MBI is associated with a more rapid decline in cognitive functions and conversion to dementia – mostly Alzheimer’s disease.

Conclusion: MBI seems to be a common condition in the elderly population, but so far the research on this condition is limited. We need more information about MBI to address the problems caused by this syndrome.

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1 Introduction

1.1 Dementia – a global health problem

Dementia is a syndrome of progressive deterioration of memory, thinking, behavior and the ability to perform everyday activities. Worldwide, around 50 million people have a dementia diagnosis, and there are nearly ten million new cases every year (1).

Dementia is a heavy burden for the patient itself. The life is changing, and it may be difficult to realize and process the pathological cause. It is also a burden for the family and the caregivers, and high levels of psychological morbidity in this group has been reported. The management of a person with dementia requires a comprehensive plan and cooperation between doctors, social and health care workers, and the family (2).

Care provided by family and friends is very important, but dementia is also a great cost for the society, driven mainly by social care needs. According to World Health Organization, the largest element of cost is professional care in the community and residential and nursing home care in high-income countries (3).

1.2 Dementia criteria in ICD-10 and DSM-5 1.2.1 ICD-10

Dementia is a syndrome that is caused by different underlying disorders (4). It contains a wide specter of symptoms with individual variations and includes cognitive as well as non-

cognitive symptoms. In Norway, the 10th version of WHOs International Classification of diseases (ICD-10) is the official diagnostic classifications system. The ICD-10 diagnostic criteria for dementia is given in Table 1.

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Table 1

Diagnostic criteria for dementia according to The International Classification of Diseases, 10^th version (ICD-10)

All of the four main points (1-4) must be met:

(1) Evidence of each of the following:

a. A decline in memory, which is most evident in the learning of new information.

b. A decline in other cognitive abilities characterized by deterioration in judgement and thinking, such as planning and organization, and in the general processing of information.

(2) Preserved awareness of the environment.

(3) A decline in emotional control or motivation, or a change in social behavior, manifest as at least one of the following

a. Emotional lability b. Irritability

c. Apathy

d. Coarsening of social behavior

(4) For a confident clinical diagnosis, (1) should have been present for at least six months.

The decline should be verified by obtaining a reliablehistory from an informant and supplemented by neuropsychological testing.

The ICD-10 criteria listed above are modified from the ICD-10 Classification of Mental and Behavioral Disorders – Diagnostic criteria for research (5).

1.2.2 DSM-5

Many dementia researchers prefer to follow the Diagnostic and Statistical Manual (DSM), which is developed by the American Psychiatric Association. In the current version (DSM-V), the term “dementia” is no longer used. The new diagnostic entity “major neurocognitive disorder” corresponds roughly to “dementia”, whereas “minor neurocognitive disorder”

corresponds to MCI. The diagnostic criteria for major neurocognitive disorder are listed in table 2.

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Table 2

DSM 5: Diagnostic criteria of major neurocognitive disorder

A. Evidence of significant cognitive decline from a previous level of performance in on or more cognitive domains

a. Complex attention b. Executive function c. Learning and memory

d. Perceptual-motor, or social cognition

Based on concern of the individual, a knowledgeable informant or a clinician that there has been a significant decline in cognitive function; and the substantial impairment can be proven by standardized neuropsychological testing

B. The cognitive decline interfere with independence in everyday activities C. The cognitive deficits are not better explained by delirium

D. The cognitive deficits are not better explained by another mental disorder Specify:

• Whether the neurocognitive disorder is due to; Alzheimer´s disease, frontotemporal lobar degeneration, Lewy body disease, vascular disease, traumatic brain injury,

substance/medication use, HIV infection, prion disease, Parkinson´s disease, Huntington´s disease, another medical condition, multiple etiologies or unspecified.

• Whether the neurocognitive disorder is with or without behavioral disturbances

• The current severity; mild, moderate or severe.

DSM 5: Diagnostic criteria of minor neurocognitive disorder

A. Evidence of modest cognitive decline from a previous level of performance in on or more cognitive domains

a. Complex attention b. Executive function c. Learning and memory

d. Perceptual-motor, or social cognition

Based on concern of the individual, a knowledgeable informant or a clinician that there has been a mild decline in cognitive function; and the modest impairment can be proven by standardized neuropsychological testing

B. The cognitive deficits do not interfere with capacity for independence in everyday activities C. The cognitive deficits are not better explained by delirium

D. The cognitive deficits are not better explained by another mental disorder Specify:

• Whether the neurocognitive disorder is due to; Alzheimer´s disease, frontotemporal lobar degeneration, Lewy body disease, vascular disease, traumatic brain injury,

substance/medication use, HIV infection, prion disease, Parkinson´s disease, Huntington´s disease, another medical condition, multiple etiologies or unspecified.

• Whether the neurocognitive disorder is with or without behavioral disturbances

The diagnostic criteria for neurocognitive disorder, are modified from DSM-5 (6).

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1.3 Mild cognitive impairment

Mild cognitive impairment (MCI) was described nearly 20 years ago (7). The term addresses patients with memory impairment beyond what is expected for age and education, yet they do not fulfill the diagnostic criteria for dementia. MCI is often seen as a type of transitional state between normal aging and dementia (8), though some MCI patients remain cognitively stable for long time and do not develop dementia.

1.4 Clinical Dementia Rating

Clinical Dementia Rating scale (CDR) is an instrument used to grade the severity of

dementia. The instrument characterizes six domains of cognitive and functional performance (9). The rating scale can be seen in appendix 1.

1.5 Neuropsychiatric symptoms in relation to dementia

Neuropsychiatric symptoms (NPS) are sometimes called “non-cognitive” symptoms or

“behavioral and psychological symptoms of dementia” (BPSD) (10). They are among the most significant challenges in dementia care (11). The following symptoms are typically considered as NPS:

• Delusions

• Hallucinations

• Agitation

• Dysphoria

• Anxiety

• Euphoria

• Apathy

• Disinhibition

• Irritability

• Aberrant motor behavior (12)

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One of the most commonly used assessment tools for NPS is the Neuropsychiatric Inventory- Questionnaire (NPI-Q). The NPI-Q is seen in appendix 2. This instrument also includes nighttime behavioral disturbances and appetite changes (13). The pathogenesis of NPS is not well understood, and the current knowledge supports multifactorial causes (14).

1.6 Mild behavioral impairment

Mild behavioral impairment (MBI) is a relatively new term and was introduced by Taragano

& Allegri in 2003 (15). In 2008 the authors defined MBI as “a later life syndrome with prominent psychiatric and related behavioral symptoms in the absence of major cognitive symptoms” and stated that MBI also appears to be a transitional state between normal aging and dementia (16). MBI can be seen as a transitional state along the behavioral and

psychological- or the non-cognitive axis, while MCI contains the cognitive symptoms axis.

1.6.1 MBI and NPI-Q

MBI includes sustaining and impactful NPS in any severity and for detection of these symptoms, NPI-Q can be used (10).

1.6.2 Diagnostic criteria for MBI

In 2016 the International Society of Advance Alzheimer’s Research and Treatment (ISTAART) introduced diagnostic criteria for MBI (17). The criteria are listed in table 3.

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Table 3

International Society of Advance Alzheimer’s Research and Treatment (ISTAART) research diagnostic criteria for mild behavioral impairment (MBI) (17)

1. Changes in behavior or personality observed by patient or informant or clinician, starting later in life (age ≥ 50) and persisting at least intermittently for ≥ 6 months. These represent clear change from the person’s usual behavior or personality as evidenced by at least one of the following:

a) Decreased motivation (e.g. apathy, aspontaneity, indifference)

b) Affective dysregulation (e.g. anxiety, dysphoria, changeability, euphoria, irritability)

c) Impulse dyscontrol (e.g. agitation, disinhibition, gambling, obsessiveness, behavioral perseveration, stimulus bind)

d) Social inappropriateness (e.g. lack of empathy, loss of insight, loss of social graces or tact, rigidity, exaggeration of previous personality traits)

e) Abnormal perception or thought content (e.g. delusions, hallucinations)

2. Behaviors are of sufficient severity to produce at least minimal impairment in at least one of the following areas:

a) Interpersonal relationships

b) Other aspects of social functioning c) Ability to perform in the workplace

The patient should generally maintain his/her independence of function in daily life, with minimal aids or assistance.

3. Although co-morbid conditions may be present, the behavioral or personality changes are not attributable to another current psychiatric disorder (e.g. generalized anxiety disorder, major depression, manic or psychotic disorders), traumatic or general medical causes, or the physiological effects of a substance or medication.

4. The patient does not meet criteria for a dementia syndrome (e.g., Alzheimer’s dementia, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, other dementia).

Mild Cognitive Impairment (MCI) can be concurrently diagnosed with Mild Behavioral Impairment.

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1.6.3 The Mild Behavioral Impairment Checklist

In 2017 a large group of experts published the Mild Behavioral Impairment Checklist (MBI- C). The checklist was made as a tool to be used by family members and other close

informants to describe and measure behavioral changes exhibited by older adults that might precede the onset of dementia based on the ISTAART- Alzheimer’s Association criteria (10).

The checklist can be seen in appendix 3.

1.7 Aim of the study

The aim of this study is to summarize the present state of knowledge about prevalence, trajectories and prognostic significance of MBI for further development of cognition, activities of daily living, survival and risk of delirium.

1.8 Previous reviews

Since the term MBI was introduced and the diagnostic criteria were published, some reviews have already been written. A review from 2013 concluded that the main problem with detection and diagnosis of MBI, was that doctors only recently had begun to recognize the existence of patients with behavioral disorders without cognitive impairment as a population at risk of developing dementia (18).

In the recent years the concept and symptoms have been more well-known, but compared to the understanding of MCI, MBI remains in early stages (19). An editorial in 2018 stated the need to improve earlier identification of MBI to earlier detect dementia and thus provide better intervention and care. The authors also concluded that awareness of MBI as a syndrome is important on the global level (20).

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2 Method

2.1 Search strategy and selection criteria

To answer the research question, this thesis is based on a literature search.

To give the best structure to the literature search on PubMed, the search terms were selected and implicated to PubMed and Web of Science. The search terms are listed below:

("Mild behavioral impairment") AND dementia AND (“Neuropsychiatric symptoms” OR Aggression OR Agitation OR Psychosis OR Hallucinations OR Delusions OR Anxiety OR Irritable Mood OR Lability OR Apathy OR Euphoria OR Disinhibition OR Depression OR Aberrant motor activities OR Sleep disturbance OR Eating disorder)

The PubMed search was done September 19^th 2019 and included all types of studies; meta- analyses, reviews, clinical studies etc. up to this date.

Web of Science was searched September 20^th 2019.

Literature and information found on reliable websites, articles and studies found in reference lists and in relevant journals are also included in this study.

PudMed was primarily used because it is generally considered to be the most complete and up-to-date database over biomedical articles of high quality and compromises over 30 million citations of biomedical literature, life science journals and online books (21).

For further selection of relevant publications, inclusion and exclusion criteria described in the next paragraph, were used.

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2.2 Inclusion criteria

Table 4

Inclusion criteria

• Defines MBI

• MBI measured via standardized instruments

• Describe prevalence and/or incidence of MBI in text

• Minimum 100 participants

• English language

2.3 Exclusion criteria

Table 5

Exclusion criteria

• Reviews

2.4 Search process

The search on PubMed gave 29 records. The search on Web of Science gave two additional records, whereas an additional record was found in a reference list, adding up to a total of 32 records. After duplicates were removed, a total of 30 records were used. See figure 1.

Trough title- and abstract reading, 17 articles did not meet the inclusion criteria, and were excluded.

After exclusions, 13 full-text articles were assessed. Based on this assessment, eight additional articles were excluded. These articles were excluded due to not being studies presenting new data, but rather discussing the relatively new term MBI (Table 7).

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2.5 Flow diagram Figure 1

The flow diagram is downloaded from PRISMA STATEMENT (22).

Records identified through PubMED

(n = 29)

Screening IncludedEligibility Identification Additional records identified through other sources

(n = 3)

Records after duplicates removed (n = 30)

Records screened

(n =30) Records excluded

(n =17)

Full-text articles assessed for eligibility

(n =13)

Full-text articles excluded, with reasons

(n =8)

Studies included in qualitative synthesis

(n =5)

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3 Results

3.1 Articles included Table 6

Author, year and study

Setting and aim Population Clinical scale used

Results

Creese, B. et. al 2019

“Mild Behavioral Impairment as a Marker of

Cognitive Decline in Cognitively Normal Older Adults” (23)

Cohort.

“To conduct a detailed analysis of the pattern of progressive

neuropsychological impairments associated with MBI.”

N = 9,931 Mean age:

62

» 75%

women

NPS ratings mapped using the MBI-C in a sample of cognitively normal elderly people over 50 years old.

MBI prevalence:

10%

MBI is associated with faster decline in attention and

working memory over a one year period.

Mortby, M. et.

al.

2018

“Prevalence estimates of mild behavioral impairment in a population-based sample of pre- dementia states and cognitively healthy older adults” (24)

Cross sectional study.

“To (1)

operationalize the recently published diagnostic criteria for MBI; and (2) used these criteria to determine the prevalence estimates of MBI in a

nationally representative population-based study.”

N = 1 377 Age range:

72-79

48% women

MBI was assessed in accordance with the ISTAART- AA diagnostic criteria for MBI using the neuropsychiatric inventory- questionnaire (NPI-Q).

MBI prevalence:

34.1%

High prevalence of MBI across the cognitive spectrum was reported. The most frequent MBI domains was impulse dyscontrol and decreased motivation. MBI was more prevalent in men.

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Page 16 Author, year

and study

Setting and aim Population Clinical scale used

Results

Sheikh, F. et. al 2018

“Prevalence of mild behavioral impairment in mild cognitive impairment and subjective

cognitive decline, and its

association with caregiver burden” (25)

Cross-sectional study.

“To (1) investigate the prevalence rates of MBI in a memory clinic population; (2) determine whether there are differences in prevalence estimates of MBI between patients presenting with SCD or MCI; and (3) determine the association of MBI with caregiver burden.”

N = 282 consecutive memory clinic patients Mean age:

62

» 50%

women

MBI assessed in accordance with the ISTART- AA research diagnostic criteria.

Operationalized definition of MBI using NPI- Q.

MBI prevalence among MCI patients:

85.3% and among SCD patients:

76.5%.

Affective dysregulation, decreased motivation and social

inappropriateness were the most present MBI domains. Decreased motivation were significantly more prevalent in MCI than SCD patients.

Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex and MCI (p<0.0001).

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Page 17 Author, year and

study

Setting and aim Population Clinical scale used

Results

Taragano, F. et.

al.

2018

“Risk of Conversion to Dementia in a Mild Behavioral Impairment Group Compared to a Psychiatric Group and to a Mild Cognitive Impairment Group” (15)

5-years prospective, longitudinal inception cohort.

“To observe and analyze patients with mild behavioral impairment (MBI), mild cognitive impairment (MCI), and a psychiatry group (PG) to compare the risk of progression to dementia.”

N = 348 Mean Age

» 71 62 % women

MBI defined as a

behavioral disturbance not meeting criteria for AD, FTD, DLB or the DSM-IV criteria for psychosis or another major psychiatric condition.

NPI-Q used to assess

psychiatric symptoms.

Of 96 MBI patients, 71.5% developed dementia over the 5 years follow up. This was significantly higher than the MCI- MBI-overlap and the MCI-group compared to the psychiatric group. The MBI- group converted most to the FD and LBD.

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Page 18 Author, year and

study

Setting and aim Population Clinical scale used

Results

Mallo, S. et. al.

2018

“Assessing Mild Behavioral Impairment with the Mild

Behavioral Impairment- Checklist in People with Mild Cognitive

Impairment” (26)

Cross-sectional study.

“To estimate the prevalence of MBI in people with MCI and to study the score distribution, sensitivity,

specificity, diagnostic utility of the MBI-C, and its correlations with

neuropsychological tests.”

N = 111 MCI participants.

Mean Age

» 70

» 64%

women

MBI assessed in accordance with the ISTART-AA research diagnostic criteria.

NPS assessed using NPI-Q.

MBI prevalence:

14.2%

MBI-C total score correlated positively with NPI-Q.

Phone administration of MBI-C is sensitive for detecting MBI in people with MCI.

MBI-C scores indicated that MCI patients has subtle NPS that were correlated to their subjective memory complaints reported by informants, depressive symptoms and negatively with IADL.

Abbreviations: MBI = mild behavioral impairment, NPS = neuropsychiatric symptoms, MBI-C = mild behavioral impairment – checklist, ISTART-AA = International Society of Advance Alzheimer’s Research and Treatment – Alzheimer’s Association, NPI-Q = Neuropsychiatric Inventory- Questionnaire, SCD = subjective cognitive decline, MCI = mild cognitive impairment, PG =

psychiatry group, AD = Alzheimer’s disease, FTD = frontotemporal lobe dementia, DLB = dementia with Lewy bodies, DSM-IV = Diagnostical and Statical Manual – 4th version, IADL = instrumental activities of daily living.

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2.7 Articles excluded after full-text reading

Table 7

Author, year, study Setting, reason why excluded and conclusion Canevelli, M. et. al.

2016

“Mild behavioral impairment: Ethical,

methodological and clinical reflections” (27)

Reflection note, not a scientific study. Useful information, but the article discuss and cite previous research articles. The article concludes that “the proposed diagnostic criteria for MBI aptly illustrate the challenges and potential limitations of preclinical diagnostic construct in the context of age- related processes that are continuous in their nature.”

Cieslak, A. et. al.

2018

“Case series of mild behavioral impairment:

toward an understanding of the early stages of

neurodegenerative diseases affecting behavior and cognition” (28)

Case report. Presentation and discussion of MBI in three different patients. The article concludes that “NPS often can emerge in later life, and may predict or precede the cognitive impairment and dementia”. It also states that “the MBI-C is a tool designed for MBI case detection, and may have utility into increasing detecting and awareness of later life onset of NPS and their link to neurodegenerative disease”.

Creese, B. et. al.

2019

“Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults” (29)

A population-based cohort study that was excluded because the study discussed the profile of MBI and the MBI-

checklist, rather than the phenomena of MBI. The study present the full spectrum of MBI symptoms (34 individual MBI symptoms) and concludes that “informant- and self- reported versions of the MBI-C perform differently and do not capture the exactly same groups, which has important implications for the study design in the cognitively normal population”.

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Dillon, C. et. al.

2013

“Behavioral symptoms related to cognitive impairment” (18)

A review that concludes that “psychiatric and behavioral symptoms are present universally in patients with dementia.

Diagnosis, characterization, and management are essential in clinical practice in order to ameliorate caregiver burden as well as to avoid frequent hospitalization and early

institutionalization”.

Elefante, C. et. al.

2019

“Mild Behavioral

Impairment: presentation of the diagnostic criteria and the Italian version of the MBI-Checklist” (30)

Not a scientific study. The article present the diagnostic criteria of MBI and the Italian version of the MBI-Checklist.

The article concludes that “the ability of the MBI-C to accurately measure MBI domains as described in the MBI criteria is an important feature of this scale”.

Ismail, Z. et. al.

2017

“The Mild Behavioral Impairment Checklist (MBI- C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia

Populations” (10)

The first presentation of the MBI-Checklist (MBI-C). The article describes the newly developed criteria for MBI for assessing the MBI construct.

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Ismail, Z. et. al.

2018

“Affective and emotional dysregulation as pre- dementia risk markers:

exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria” (19)

Review. The article concludes that “symptoms of affective and emotional dysregulation are common harbingers of neurodegenerative change and progressive decline in several pre-dementia syndromes. Despite this, there are limited interventions to prevent and treat these symptoms and ensuring dementia syndromes”.

Mortby, M. et. al.

2018

“Special Issue on mild behavioral impairment and non-cognitive prodromes to dementia”(20)

Guest editorial article that gives an overview of the current research agenda to validate the construct of MBI. The article concludes that we need more knowledge of “the prognostic utility of specific MBI domains, the role of symptom severity, and the description of NPS as a consequence of neurodegenerative disease”.

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3.1 Review of the included articles

Among the articles included in this study, the prevalence of MBI varied among the groups with altered cognitively state. The prevalence among the patients not meeting the diagnostic criteria for either dementia or MCI varied between 10 % and 28 %. The prevalence of MBI in the MCI groups varied between 14 % and 85 %.

The articles that described the MBI domains found that the most common domain among the cognitively normal men and women, were impulse dyscontrol (17 %) and decreased

motivation (16 %). Impulse dyscontrol and decreased motivation were found in 35 % and 32

%, respectively, among the MCI patients in the same article (24). Another article found that affective dysregulation, impulse dyscontrol, decreased motivation, social inappropriateness, abnormal perception or disturbed thought content are the most present domains in individuals suffering from MBI (25).

Only one article looked into the caregiver burden, and found that it was 3.35 times higher among the MBI patients compared to patients with subjective cognitive decline (SCD).

Caregiver burden was assessed using the 22-item Zarit Caregiver Burden Interview, a research guide for people working with dementia (31). The caregiver burden scores were significantly higher in patients with MBI compared to those without (p < 0.0001). The authors also found that affective dysregulation, impulse dyscontrol, decreased motivation, social inappropriateness and abnormal perception or thought content in MBI were all significantly associated with greater caregiver burden.

In addition, individuals with both MCI and MBI (p < 0.001), compared to SCD only, MCI only (p = 0.78) and SCD and MBI (p < 0.0001), had a greater caregiver burden score (25).

The only study that described gender differences found that 56 % of the individuals meeting the MBI criteria were men (24).

The studies that describe the development of dementia and association of decline in cognitive functions, found that the presence of MBI was associated with a more rapid decline in

attention and working memory over a one year period (23).

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Taragano et. al. followed 348 patients with MBI (n = 96), MCI (n = 87) and general

psychiatry disorders (PG) (n = 165) during a five years period until conversion to dementia or exclusion. During the follow-up time, over one third (36 %) converted to dementia. As many as 72 % of the MBI patients, 60 % of the MCI-MBI-overlap group, 38 % of the MCI patients and 14 % of the PG-group converted.

The article of Taragano et. al also found that the most common form of dementia diagnoses among patients converting to dementia were Alzheimer’s disease (MCI 83 %, MBI 27 %, PG 22 %), frontotemporal lobe dementia (FTD) – (MCI 17 %, MBI 45 %, PG 30 %) and Lewy body dementia (LBD) (MCI 0 %, MBI 28 %, PG 48 %). This means that the majority of the MCI patients tend to convert to Alzheimer’s dementia, while the MBI patients tends to convert to a wider range of neurodegenerative diseases, in this trial; FTD, followed by LBD and Alzheimer’s (15).

None of the included articles examined or discussed the risk of developing delirium.

Mallo et. al. also explored the possibility of phone administration to detect MBI in patients with MCI and found that this is a highly sensitive (100 %) way of detecting MBI. The phone administration took 10-15 minutes and minimized the travel time to the health center and optimized the retention (26).

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4 Discussion

The ISTAART research diagnostic criteria for MBI include a wide range of symptoms; a specter including decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness and abnormal perception or thought content (17). In addition to these symptoms, the checklist outlines that the function in daily life is maintained.

The data from this review suggest that the prevalence of MBI varied among the groups with varying cognitive function. Since the term MBI is relatively new and was introduced as late as in 2003 (15), few studies of this condition have so far been published. The findings in these studies and the reported prevalence of MBI may therefore differ.

Both NPI-Q and MBI-C are used all over the world and by many different clinicians. This may explain the different prevalence of the diversity of symptoms in the different populations.

The clusters of symptoms with the most profound impact overall was impulse dyscontrol and decreased motivation. We need to take the following question into consideration; do these clusters actually dominate in the elderly population, or is the raised prevalence of these symptoms caused by something else?

My findings indicate that the need for knowledge is still huge. The transition to dementia is very individual. Are MBI symptoms in the elderly populations a natural part of growing old or are they a part of developing a dementia diagnosis?

Studies have found that the presence of NPS is associated with an increased risk of

developing dementia, and that behavioral changes tend to go longer unnoticed, compared to memory problems. The concern about losing memory is a well-known problem among the elderly. Memory problems often seem to be the bigger problem for the elderly and their caregivers (15). MBI transition to dementia is seen in a wider range of neurodegenerative diseases and is associated with faster decline in attention and working memory in this study.

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Taking care of someone with cognitive decline can be a great burden for the caretakers, especially when the patient has NPS (32). One article reported that caregiver burden was significantly higher among caretakers with MBI patients compared to those without MBI.

Behavioral problems seem to give most caregiver burden and is related to both depression and distress among the people taking care of the elderly (33).

As mentioned earlier, the gender distribution among patients with MBI differ. MBI is seen more frequently in men than in women. This may be due to risk factors, where sex differences among MCI-patients are well documented, and often found more frequently in men (34) (35) (36).

Phone administration were found to be highly sensitive to detect MBI, and with this knowledge it can be possible do diagnose and detect MBI in situations where it can be difficult for patients or caregivers to travel to the clinics. This can also improve the accessibility for follow up-situations and to keep track of trajectories.

The methodologic strengths in this study is that the literature search was systematically done.

The search terms was carefully chosen to incorporate the MBI-term and implicated into both PubMed and Web of Science. All the relevant articles where chosen carefully.

One limitation is the low number of publications found to be relevant for this article. This is a limitation, but also an important finding to acknowledge that the research published is very limited. The search was done in September 2019 and since then, new articles have been

written. The limited data may be caused by the relatively new knowledge about the term MBI.

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5 Appendix

Appendix 1 – CDR Scoring table

The CDR Scoring Table is downloaded from the webpage of Washington University in St.

Louis (37).

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Appendix 2 – Neuropsychiatric Inventory-Questionnaire

The symptoms should be circled “yes” only when the symptoms has been present for the last month. The severity is defined as 1 = mild, 2 = moderate, 3 = severe. The distress represent how much the symptoms bother the patients, where 0 = not distressing at all, 1 = minimal distress, 2 = mild distress, 3 = moderate distress, 4 = severe distress and 5 = extreme or very severe distress.

Delusions Does the patients have false beliefs, such as thinking that others are stealing from him/her or planning to harm him/her in some way?

Yes No Severity: 1 2 3 Distress: 0 1 2 3 4 5

Hallucinations Does the patients have hallucinations such as false visions or voices?

Does he or she seem to heat or see things that are not present?

Agitation/ Aggression Is the patient resistive to help from others at times, or hard to handle?

Depression/

Dysphoria

Does the patient seem sad or say that he or she is depressed?

Anxiety Does the patient become upset when separated from you? Does he or she have any other sign of nervousness such as shortness of breath, sighing, being unable to relax, or feeling excessively tense?

Elation/ Euphoria Does the patient appear to feel too good or act excessively happy?

Apathy/

Indifference

Does the patient seem less interested in his or her usual activities or in the activities and plans of others?

Disinhibition Does the patient seem to act impulsively, for example, talking to strangers as if he or she knows them, or saying things that may hurt people’s feelings?

Irritability/

Lability

Is the patient impatient and cranky? Does he or she have difficulty coping with delays or waiting for planned activities?

Motor Disturbances Does the patient engage in repetitive activities such as pacing around the house, handling buttons, wrapping string, or doing other things repeatedly?

Nighttime Behaviors Does the patient awake you doing the night, rise too early in the morning, or take excessive naps during the day?

Appetite/ Eating Has the patient lost or gained weight, or had a change in the type of food he or she likes?

The NPI-Q is retrieved from Alzheimer’s Association (38).

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Appendix 3 – Mild Behavioral Impairment Checklist (MBI-C)

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The test is downloaded from www.MBItest.org (39).

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