Clinical practice guidelines for assessment and management of mild neurocognitive disorder

INTRODUCTION Today, neuroscience has progressed to understand that dementia is actually a late diagnosis. Just as cholesterol plaques start in the vascular system as early as the first decade of life, so too brain degeneration may predate manifestation of frank symptoms by 2–3 decades. Therefore, it is important to understand if clinically there is a gray zone between apparent normal brain functioning and obvious brain decline. This gap is what mild cognitive impairment or mild neurocognitive disorder (Mild NCD) is. A seminal discussion in 2003 led to acceptance of Mild NCD as a separate entity and the definition based on Petersen’s criteria. Subsequently, these were modified to Winblad criteria and those defined by NIA-AA (National Institute of Ageing and Alzheimer’s Association) as well as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (which spoke of Mild NCD). The common thread in all of these was subjective recognition of cognitive errors, objective decline in neuropsychological tests, and relatively intact ability to carry on with activities of daily living, the combination of which could lead to adequate distress and anxiety.[1] Hence, systematic research of the same and the approach to assessment and care are really the need of the hour. In India, the research is even more limited, and hence, this guideline, which is a combination of the best advised practices, and those followed easily in the subcontinent, so it can be easy for the treating psychiatrist to approach and manage. PROCESS OF DEVELOPMENT The development of the Clinical Practice Guidelines (CPG) for the assessment and management of Mild NCD was a rigorous and systematic effort led exclusively by a team of psychiatrists from leading institutions across India. The guidelines were crafted based on an extensive review of the latest scientific literature, including national and international guidelines such as those from the National Institute on Aging-Alzheimer’s Association (NIA-AA), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and the International Classification of Diseases (ICD-11). This process was driven by the need to address the specific challenges and nuances of diagnosing and managing Mild NCD within the Indian population. The expert team engaged in multiple rounds of discussions and deliberations to ensure that the guidelines are evidence-based, clinically sound, and tailored to the Indian context. Following this, the draft was deliberated in an IPS workshop, incorporating the inputs of expert professionals throughout the country. The focus was on creating a comprehensive resource that reflects both the current scientific understanding of Mild NCD and the practical realities faced by psychiatrists in India. The resulting guidelines aim to standardize and enhance the quality of care provided to individuals with Mild NCD, ensuring that psychiatrists have a reliable and relevant framework for diagnosis and management. These guidelines may be modified by the clinicians as per the individual’s need and feasibility, as per the available facilities and setup. COGNITIVE RESERVE When discussing about Mild NCD, it becomes imperative to understand what cognitive reserve is and how to assess it. Cognitive reserve (CR) is nothing but the brain’s ability to cope with neuropathology/neurodegeneration by exploiting pre-existing cognitive processes and/or compensatory mechanisms, which is supposedly built through a number of factors over the years. It reflects the brain’s flexibility and efficiency in utilizing available resources to maintain cognitive function despite aging or disease [Figure 1].Figure 1: Cognitive reserve and its significanceAssessing cognitive reserve is crucial for understanding individual differences in susceptibility to cognitive decline and dementia. It helps in identifying those at higher risk and in tailoring interventions that can bolster cognitive reserve through lifestyle modifications and targeted cognitive training. Although there are no gold standard tests available, certain proxies are cumulatively reflective of CR [Table 1].Table 1: Proxies of CR and their assessment[ 2 , 3 ]Some scales also have been formulated using one or more of the above proxies or domains but are not widely used and researched [Figure 2].Figure 2: Scales for assessment of CR[ 2 , 3 ]MILD NCD AS A DIAGNOSTIC ENTITY The transition between normal aging and very early-stage dementia has been defined using various terms, such as Mild NCD, dementia prodrome, incipient dementia, and isolated memory impairment. Over the years, Mild NCD has become a widely used term and will be used here for the purpose of discussion. MILD NCD is positioned between normal aging and early dementia on the continuum, with overlapping stages at both ends of the MILD NCD [Figure 3], indicating that distinction between normal ageing and MILD NCD can be subtle and clinically challenging. However, Mild NCD has gradually been established as a distinct diagnosis, with specific criteria and intervention strategies.[4]Figure 3: The cognitive continuum showing the overlap in the boundary between normal ageing and Mild NCD and early dementiaSeveral terms have been used in connection to cognitive decline before dementia, apart from MCI over time. Subjective cognitive impairment (SCI) is a self-perceived decline in cognitive abilities, particularly memory, without objective evidence from standardized cognitive tests. It represents the earliest symptomatic manifestation in the continuum from normal aging to dementia. Other terminologies which have been used are, for example, benign senescence forgetfulness, age-associated cognitive decline (AACD), age-associated memory impairment (AAMI), cognitive impairment no dementia (CIND), and very recently used Mild NCD in DSM-5 [Table 2].[5]Table 2: Historical terminologies used for cognitive declinePATHOLOGY IN MILD NCD Along with changes in the nomenclature, simultaneous changes occurred in the understanding of Mild NCD, summarized in Table 3. In addition to symptoms and cognitive assessments, brain pathology was also deliberated. The protein theories of Mild NCD emphasize the significant role of abnormal protein accumulation and aggregation in the brain, which can lead to cognitive decline. Table 4 summarizes the key proteins involved, their roles in Mild NCD, and underlying mechanisms.Table 3: Evolution of Mild NCD as an entityTable 4: Protein theories in etiopathogenesis of Mild NCD[ 7 ]SUBTYPES OF MILD NCD Mild NCD is heterogeneous in presentations, depending upon the affected cognitive domain. Due to this, it has also been classified on the basis of the cognitive domain affected. This classification relates to underlying etiology and pathology, clinical presentation, and outcomes. Figure 4 shows various subtypes and their probable outcome.[8] Today, we understand that this classification is more clinical and less etiopathological and probably too simplistic to understand Mild NCD. Nevertheless, it is important for the clinician to know.Figure 4: Clinical subtypes of MCI and their probable outcomesPROGRESSION OF MILD NCD The course of Mild NCD is variable. It may not always convert to dementia. Around 20–40% cases appear to improve over time on retesting. After diagnosis, the subtype may change on follow-up. A single domain particularly seems to be at risk of this shift. However, some have found that all Mild NCD subtypes either convert to dementia or retain their status. Rates of progression to dementia vary in the range of 20–40% (10–15% per year) with a few outliers at the lower and higher ends of the spectrum, around 80% cases in approximately 10 years, which keeps on increasing exponentially each year.[8] Certain factors are associated with increased risk of progression to dementia which should be specifically looked for while assessment [Table 5].Table 5: Risk factors for progression of Mild NCD to dementia[ 8 ]DELAY IN SEEKING TREATMENT Mild NCD may although affect one or more cognitive domains but does not interfere with a person’s capacity of independence in everyday activities and often gets overlooked, leading to delays in consultation, along with various other reasons [Table 6].Table 6: Reasons for delay in seeking consultation in person with Mild NCDNEED FOR ASSESSMENT AND EARLY DIAGNOSIS IN MILD NCD The need for diagnosis and intervention in Mild NCD is often questioned owing to the mild nature of its symptoms. Evidence suggests that Mild NCD may remain stable, return to neurologically intact conditions, or progress further to dementia. However, the risk of progressing to dementia compared to age-matched controls is higher, thus indicating the pathologic disease state of Mild NCD rather than normal aging. Mild NCD needs comprehensive assessment and timely interventions. Various reasons are listed in Table 7.Table 7: Need for assessment and early diagnosis in Mild NCDASSESSMENT OF PERSONS WITH SUSPECTED MILD NCD Any patient suspected of having Mild NCD should undergo detailed clinical evaluation and systematic investigations. A comprehensive history and physical examination [especially central nervous system (CNS) examination], focusing in detail on the status of cognitive functions, status of activities of daily living, medication use, neuropsychiatric evaluation, incorporating laboratory testing, and neuroimaging, are important components of this assessment [Figure 5].Figure 5: Overview of assessment in cases of a person with suspected Mild NCDHistory taking Taking a comprehensive history in patients with Mild NCD is crucial for accurate diagnosis and management. The history may focus on clarifying the points as mentioned in Table 8.Table 8: Components of history to be elicited in patients with suspected MILD NCDThe history should incorporate the following considerations in detail: Cognitive symptoms: Detailed history of cognitive symptoms needs to be elicited [Table 9].Table 9: Pointers in history of cognitive symptoms in suspected Mild NCD The other important parameters to be assessed in history history (points b to k) are summarized in Table 10.Table 10: Specific parameters to be explored in each section of historyExamination Neurological Some of the relevant findings of neurological system examination are listed in Table 11.[9] In the briefest neurological examination, assessing extraocular movements and gait is crucial whenever feasible.Table 11: High-yield neurologic examination in the assessment of cognitive symptomsNeuropsychological assessments The mental state examination in a suspected case of cognitive impairment requires detailed evaluation of higher mental functions. This would include testing the cognitive domains already elaborated in the section of ‘History taking’. Some of the common tests and their usefulness are listed in Table 12.[9,10] The first six may be done by the sole practitioner in OPD as well.Table 12: Cognitive assessment in examination of patient with suspected Mild NCDDiagnosis Both DSM-5 and ICD-11 include mild cognitive impairment under the category of Mild NCD, with nearly similar diagnostic criteria.[11,12] ICD-10 mentions the diagnosis of ‘Mild Cognitive Disorder’ (F06.7) under the head of ‘Other mental disorders due to brain damage and dysfunction and physical disease’[13] [Table 13].Table 13: Diagnostic criteria for mild NCD in different classification systemsConsiderations while making a diagnosis of Mild NCD Excessive focus on subjective symptoms could lead to missing the diagnosis, where the patient lacks insight and/or the family is in denial. Excessive focus on objective assessments may lead to missing the diagnosis in high functioning individuals, whose currently ‘normal’ performance might be a ‘decline from his/her baseline’. Assessment of the cognitive reserve of the individual (as has been explained earlier). Individuals with high cognitive reserve may not show symptoms of Mild NCD until they have a significant amount of brain pathology, which may delay the diagnosis of Mild NCD. Second, standard cognitive tests might not be sensitive enough to detect Mild NCD in such individuals. The neuropsychological assessment has a role in reaching to diagnosis. These tests, with performance compared against age-appropriate norms and educational and cultural backgrounds, are a critical part of the standard evaluation of NCDs, particularly that of Mild NCD. It is also interesting to note that none of the common definitions of Mild NCD includes advanced age as a criterion, in spite of the fact that most of the research in the domain occurs in the geriatric population and is presumed to be a disorder of old age. Differential diagnosis When talking about making a diagnosis of mild NCD, it is crucial to consider the following common differential in relation to Mild NCD [Figure 6].[11]Figure 6: Diffrential diagnosis of Mild NCDInvestigations Labs The diagnosis of Mild NCD is based on the diagnostic criteria. However, there are a number of underlying factors or causes which may be causative or contributory to the condition. This has been taken into cognizance by the specifier ‘Another Medical Condition’ of the Mild Neurocognitive Disorder in DSM-5.[11] Similar to dementia, Mild NCD too has many reversible causes, which, although less commonly, show good prognosis with optimum treatment of underlying conditions. Thus, such potentially reversible causes should be thoroughly investigated. Some of the common ones are listed in Figure 7, along with the mode of assessment.[14–16] However, it is essential to elicit symptoms and signs as well, while clinical assessment, which would provide clues to the etiology and accordingly the investigations, may be conducted. For example, metabolic causes generally have some or the other clinical manifestation, which can be identified. Atrial fibrillation may cause small, undetectable embolic events, similar to small strokes or transient ischemic attacks, leading to Mild NCD and ultimately vascular cognitive impairment.Figure 7: Potential reversible causes/contributory factors for Mild NCD and their assessmentNeuroimaging Neuroimaging has not been routinely recommended in diagnosis of Mild NCD but may be helpful in evaluating the overall brain structure, in addition to serving the following purposes: Identifying underlying causative conditions like brain tumors, normal pressure hydrocephalus, vascular malformation, and strokes. Serving as a potential biomarker for progression to Alzheimer’s dementia (AD). However, there is lack of consensus of different guidelines on this. Advances in both structural and functional neuroimaging have been providing valuable insights into the structural, functional, and biochemical alterations in the brain, enabling the physicians to the diagnosis of Mild NCD and in its progression to dementia more neuroimaging findings are summarized in Figure 8: Neuroimaging findings in Mild for have been to improve clinical of that process In relation to various are used for for example, and In Alzheimer’s dementia, the earliest changes in the specifically in the and damage in the to a in its of the is a for assessing pathology, suggests the of the underlying disease and is an early for have a between and disease changes in the to Alzheimer’s have been in The and in diagnosing early-stage Alzheimer’s disease and its progression in patients with MILD NCD. for these can be valuable if testing may provide potential testing has not been or recommended in of the The important are summarized in Figure Figure 9: and of testing in Mild NCD should be Detailed neuropsychological assessment Assessment of of cognitive tests, to and cultural is crucial part for evaluation of patients with Mild NCD. The DSM-5 does not specific neuropsychological tests, but these tests can assess changes in six key of memory, and However, no such assessment all these The performance within 2 standard range and Some of the used tests along with their are listed in Table of Neurocognitive assessment in relation to Mild addition to clinicians should also on cognitive functioning from using standardized assessment such as the on Cognitive in the and the Other tests used are for Mild Cognitive and Assessment of Assessment of functional status is also important to Mild NCD from dementia. are of in activities of daily are in Mild NCD. functional using from an A of or higher has over in mild cognitive impairment from dementia. Assessment of It is a and reliable which performance in daily Assessment of and symptoms The and symptoms of Mild NCD and the distress may be assessed using and a of the and for by Figure 10 an to approach a person with suspected Mild 10: Assessment approach to a person with suspected Mild NCD that can be routinely followed by MILD NCD is due to in in it from normal aging or dementia, and lack of management on early and to maintain cognitive function and delay progression to dementia [Figure is and management on due to lack of medication and in This to some to the of its management [Table 11: of in Mild to management of Mild NCD[ , of management for Mild NCD include a care for MILD NCD whenever managing overall for disease and [Table patients and to their activities and to as is a to the management of management in Mild NCD[ can be at various for and managing MILD NCD for risk The factors for Mild NCD as are a potential for intervention to the risk of Mild NCD at a The common ones along with intervention are listed in Table for risk in Mild NCD[ , of reversible causes of Mild NCD in the assessment factors can to or even cause Mild NCD. these factors are often and even some are easily and can improve of underlying causes is the in Table causes of Mild NCD and their management an and for treating Mild NCD and early in In it brain cognitive decline by compared to of cognitive decline of 10 2 Risk of particularly in individuals with a Other include brain and can include and and is Mild NCD due to and early recommended for patients with evidence of dementia and should be used in due to the risk of around need of and lack of need to be to ensure the there are no other by the for treatment of Mild NCD. Table in management of dementia, in NCD, without while various and interventions have been none have significant in the progression of Mild NCD to dementia. the focus has to treatment for Mild NCD management of neuropsychiatric symptoms should be done by symptomatic management using as in the population may be for symptoms like and is evidence of of brain like and current in Mild NCD. research with standardized is to assess the of the same on Mild management Cognitive for Mild NCD to improve cognitive function and enhance quality of and targeted interventions are essential as they can lead to symptomatic neuropsychiatric and ultimately improve for individuals with Mild NCD. This can be classified into cognitive cognitive and cognitive approach has distinct and of activities [Table of cognitive and in interventions are well researched and found to have on the cognitive functioning of individuals. These and the specific cognitive domain or the overall These may be or in at or at by a or family with of a [Table may be as in the in the draft is mentioned in the for Mild NCD It is that lifestyle can the risk of of cognitive decline and to cognitive in individuals. Table with a few for the The the role cognitive reserve and lifestyle have in cognitive decline. The findings of the that higher ability in life, mental and physical and the risk of cognitive impairment and dementia despite the of Alzheimer’s In a similar the that of in is associated with a risk of cognitive impairment and dementia, the and of the of in cognitive interventions in Mild NCD[ to management of Mild NCD interventions on detailed assessment, a management should be in with the patient and family which includes relevant cognitive and lifestyle along with specific and treatment resources and to the patient and family the interventions. to progress and to the tailoring a management to the distinct needs of the patient and family in the it is to a that cognitive and improve quality of for individuals with Mild NCD. This approach that the interventions are and with the lifestyle and interventions in Mild NCD interventions a crucial role in managing Mild NCD and both patients and their These interventions can improve the quality of life, and enhance Some key of are listed in Figure 12: for care of patients with Mild assessment in Mild NCD The following should be in for those with Mild A cognitive that is A history from A functional capacity in Table Table assessments in Mild NCD[ , and research considerations in mild NCD A number of considerations with individuals with Mild NCD may in of clinical and other research The clinician may also to assessment, diagnosis and management of such individuals. Table summarizes the key points and to and research in Mild NCD and and mild NCD to the ability of an individual to understand the and of available an and that Mild NCD represents an or between normal aging and more of cognitive impairment and thus about the capacity of these individuals to and their such was in research and clinical which was in the are [Table to capacity of with Mild NCD in various OF IN MILD NCD of the assessment and management of Mild NCD is in Figure 13: Overview of management in Mild assessment and management of Mild NCD is essential to its progression and to enhance the quality of of the individuals. and diagnosis, utilizing clinical assessment, laboratory tests, and neuropsychological testing, for timely including cognitive and lifestyle can address both cognitive and neuropsychiatric symptoms associated with Mild NCD. and managing Mild symptoms is essential in and overall patient outcomes. assessments are crucial to disease progression and treatment research and of tests, and interventions are to improve diagnostic and treatment to these clinical clinicians can ensure a and approach to the assessment and management of Mild NCD, with Table serving as a for Clinical to approach Mild and of are no of