Clinical Practice Guidelines for Management of Dementia.

Abstract

INTRODUCTION Indian Psychiatric Society (IPS) published Clinical Practice Guidelines (CPGs) for management of dementia, in the year 2007. (http://www.indianjpsychiatry.org/cpg2007.asp). The current version of the CPG is an update of the earlier version of CPGs for management of dementia There were three separate CPGs for management of dementia, one each for Reversible Dementias, Alzheimer's Disease and Vascular Dementia, Please note that the present CPG on dementia deals all types of dementia together. The current version of the CPGs for dementia in elderly must be read in conjunction with the previous version of CPGs for dementia. The focus of the present CPG is to provide suggestions and clinical tips to differentiate dementia syndrome from other clinical conditions, identify the subtypes of dementia and then offer suggestions for management. These guidelines only provide a broad framework for assessment, management and follow-up of older people with dementia. While most of the recommendations are evidence based, these guidelines should not be considered as a substitute of professional knowledge and clinical judgment. The recommendations made as part of these guidelines should be tailored to address the clinical needs of the individual patient and the treatment setting. AGING, DEPRESSION AND DEMENTIA Before we examine the management of dementia, let us look at the issues related to the clinical diagnosis of dementia. Mental health problems and disablement are frequent in late life. Dementia and depression are two major mental health problems in late life. It is well known that the prevalence of dementia increases steadily with age. Normal aging itself is associated with age related decline in cognitive functions. Depressive symptoms are more common in later years of life. The differentiation between depressive disorder and a cognitive disorder can be problematic in this age group. There are many symptoms which can be seen in both in depressive disorders as well as in cognitive disorders. Depression can co-exist with mild cognitive impairment (MCI) a condition which is being increasingly recognized as an important entity. MILD COGNITIVE IMPAIRMENT AND DEMENTIA Mild cognitive impairment (MCI) is a controversial entity but remains a useful construct in terms of targeting interventions to prevent dementia. MCI detection relies largely on subjective memory complaint (SMC) as a presenting symptom. However SMC is heterogeneous in its etiology and poorly predicts medium-term dementia risk. The differentiation of early dementia from MCI depends on the level of cognitive impairment and the resultant disability. Cognitive impairment in dementia causes significant impairment in instrumental activities of daily living and this is known to increase with time. Most diagnostic criteria use the resultant disability as an important differentiating feature. However reliance on informant reports can be problematic as that could be influenced by the social context, expectations of the informant and his or her ability to know and the current level of functioning of the older person. DEMENTIA SYNDROME Dementia is a syndrome due to disease of the brain, usually chronic, characterized by a progressive, global deterioration in intellect including memory, learning, orientation, language, comprehension and judgment. It mainly affects older people, after the age of 65 years. Then onwards, the prevalence doubles with every five year increment in age. Dementia is one of the major causes of disability in late-life. People with dementia have difficulty in living independently and have difficulties in social and occupational functioning. The disabilities progress with the severity of dementia Cognitive changes that are part of normal aging process has to be differentiated from the dementia syndrome. This is difficult in early stages of dementia. Age related changes are more frequent in those who are in their eighties and nineties. Propensity to develop transient cognitive problems like delirium increases with age and in the presence of cognitive impairment Evaluation of cognitive symptoms Cognitive symptoms can be due to many conditions and dementia is only one of them. Delineation of the syndrome of dementia and differentiating it from other cognitive disorders is the first task. Other assessments can then follow. The suggested assessments are best carried out as part of the initial evaluation though it might take a few sessions to complete. See table -1.Table 1: Assessment for dementiaThe following assessments will help in making a clinical diagnosis of dementia : See the flow chart below. History of Cognitive Changes History taking is the main tool in eliciting and evaluating the nature and progression of cognitive decline. Choose an informant who knows about the person's current and past personal, social and occupational functioning. A reliable informant should be interviewed separately in person. This will allow discussion of a certain information which may otherwise be difficult in the presence of the patient. While doing the assessments, one has to be mindful of the family's culture, values, primary language, literacy level and also the decision making process. A thorough history should include details like the mode of onset of cognitive decline which affects multiple cognitive domains. The pattern progression, clinical manifestations of cognitive dysfunction, behavioral as well as personality changes will have to be enquired into. Subjects or informants can be asked if the person is forgetful about recent events; especially amnesia for events which happened hours or days back. Does the person forget the fact that he/she had a meal some time after having the meal? Does the person tend to ask the same questions repeatedly even though this was answered many times. Is the person unable to recall where they’ve placed things and often searching for things? A review of current medication is very important. Enquire if there is worsening of cognitive symptoms after initiation of a certain new medication. Details regarding the use of all medications, including over-the-counter products, may be collected. See if the person is on medications with anti-cholinergic effects which can worsen cognitive functions. Importance of Identification of Delirium Delirium is an important differential diagnosis of dementia. Patients with pre-existing dementia could present for the first time with superimposed delirium. Sudden worsening of cognitive functions and appearance of behavioural symptoms should alert the clinician to the possibility of delirium. Delirium is a medical emergency signs that needs to be identified early and evaluated immediately. A diagnosis of dementia cannot be made if the cognitive deficits occur exclusively during the course of delirium. Delirium is characterized by a disturbance of consciousness and a change in cognition that develop over a short period of time. The disorder has a tendency to fluctuate during the course of the day, and there is evidence from the history, examination or investigations that the delirium is a direct consequence of a general medical condition, substance intoxication or withdrawal. The ICD 10 diagnostic criteria for Delirium is given below ICD 10 CRITERIA FOR DELIRIUM, NOT INDUCED BY ALCOHOL AND OTHER PSYCHOACTIVE SUBSTANCES Clouding of consciousness, i.e. reduced clarity of awareness of the environment, with reduced ability to focus, sustain, or shift attention. Disturbance of cognition, manifest by both: impairment of immediate recall and recent memory, with relatively intact remote memory; disorientation in time, place or person. At least one of the following psychomotor disturbances: rapid, unpredictable shifts from hypo-activity to hyper-activity; increased reaction time; increased or decreased flow of speech; enhanced startle reaction. Disturbance of sleep or the sleep-wake cycle, manifest by at least one of the following: insomnia, which in severe cases may involve total sleep loss, with or without daytime drowsiness, or reversal of the sleep-wake cycle; nocturnal worsening of symptoms; disturbing dreams and nightmares which may continue as hallucinations or illusions after awakening. Rapid onset and fluctuations of the symptoms over the course of the day. Objective evidence from history, physical and neurological examination or laboratory tests of an underlying cerebral or systemic disease (other than psychoactive substance-related) that can be presumed to be responsible for the clinical manifestations in A-D. Common causes of Delirium include: Infection (e.g. pneumonia, urinary track infection, etc.) Drugs (particularly those with anticholinergic side effects e.g. antidepressants, anti-parkinsonian /anticholinergic drugs, sedatives, etc.) Cardiological (e.g. myocardial infarction, heart failure) Metabolic imbalances (e.g. secondary to dehydration, renal failure) Endocrine and metabolic (e.g. cachexia, thiamine deficiency, thyroid dysfunction) Neurological (e.g. stroke, subdural haematoma, Epilepsy) Substance intoxication or withdrawal (e.g. alcohol) Respiratory (e.g. pulmonary embolus, hypoxia). Clinician should take care, not to misdiagnose Delirium as Dementia and also not to miss the diagnosis of Delirium when it is superimposed on dementia. When there is clinical suspicion of delirium, the efforts should focus on identifying the causes. Delirium in older people are most often multifactorial in etiology and identification of the underlying conditions would enable us to provide interventions to reverse/modify them. The evaluations need to be comprehensive so that all common causes can be ruled out. Prolonged delirium could lead to more neuronal damage and accelerate cognitive decline by impacting the cognitive reserve The interface between Delirium & Dementia Delirium and dementia are two major causes for cognitive impairment in later years of life. Though these two conditions had been conceptualized as distinct, mutually exclusive entities, it can be difficult at times to differentiate between them. Delirium in late life is often superimposed on pre-existing dementia and can be the reason for help seeking. Dementia is the leading risk factor for delirium in an older person. Occurrence of delirium in turn is a risk factor for subsequent dementia in older people without pre-existing dementia. The clinician needs to differentiate between three possible scenarios namely Delirium with no features suggestive of pre-existing dementia dementia with no features suggestive of delirium dementia with superimposed delirium. See table-2 for broad guidelines for making this distinction, which by no means, will be easy in a given clinical setting. When faced with uncertainty, it is better to attribute the symptoms to delirium and manage it as delirium. This will allow careful monitoring and detailed evaluation to identify modifiable conditions/factors.Table 2: Differentiation between Delirium & DementiaDementia with Psychotic Symptoms and Schizophrenia Presence of BPSD, especially delusions with or without hallucinations in mild to moderate dementia can resemble schizophrenia or other psychotic conditions in late life. The key differentiating features here are history of progressive cognitive decline which has onset prior to the development of psychotic symptoms the presence of clinically significant impairment in multiple cognitive domains on clinical evaluation. This distinction is rather easy when there is long duration of illness starting from adulthood. But it could be difficult when psychotic symptoms have onset after the age of 60 years and also in situations where it is difficult to test cognitive functions due to active psychotic symptoms. One could also come across individuals who after many years of illness with onset during adulthood, either schizophrenia or bipolar disorder, present with cognitive decline and clinical features suggestive of dementia. In such situations an additional diagnosis of dementia can be made apart from the diagnosis of the pre existing mental health condition. See table-3 for some clinical tipsTable 3: Psychosis of AD compared with Schizophrenia in the elderlyDifferentiation between Dementia and Mild Cognitive Impairment The differentiation between early dementia and mild cognitive impairment can be difficult at times but efforts to make that distinction is always warranted. DSM 5 uses the term Mild Neurocognitive Disorder to refer to this condition. ICD 10 does not have specific criteria. The following DSM 5 criteria may be used as a guide for clinical diagnosis of Mild Cognitive Impairment. DSM 5 criteria for Mild Cognitive Impairment Evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual motor, or social cognition) based on: Concern of the individual, a knowledgeable informant, or the clinician that there has been a mild decline in cognitive function; and A modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment. The cognitive deficits do not interfere with capacity for independence in everyday activities (i.e., complex instrumental activities of daily living such as paying bills or managing medications are preserved, but greater effort, compensatory strategies, or accommodation may be required). The cognitive deficits do not occur exclusively in the context of a delirium. The cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia). Behavioral disturbance (e.g., psychotic symptoms, mood disturbance, agitation, apathy, or other behavioral symptoms The diagnostic challenge in MCI here is in the assessment of “significant impairment in functional ability,” which is required for the diagnosis of dementia. There is also the controversy about the best way to objectively measure memory loss. Early recognition of the condition may help the clinician to monitor the progression of cognitive and other symptoms and the later conversion to dementia. This might allow potential use of evidence based preventive interventions as and when they become available. The recognition of MCI as a diagnostic allows us to have a better understanding of the nature of mild memory loss, which is far more common than dementia among the older segments of the population. Table-4 lists out the main differences between the two clinical conditionsTable 4: MILD COGNITIVE IMPAIRMENT Vs DEMENTIAAssessment of Dementia Syndrome We need to rule out delirium and mild cognitive disorder before we make a clnical diagnosis of dementia. Then one should apply and see if the person meets the diagnostic criteria for Dementia. If that is met, then there is a need to make further evaluations. The next part of evaluation is aimed at establishing the cause for the dementia syndrome. Types and Causes of Dementia Dementia is a syndrome which can be caused by many diseases. After the clinical recognition of dementia syndrome, the evaluations shall focus on identifying the cause of dementia. Causes can be broadly classified as “reversible causes’ and “Irreversible” causes. Though “Reversible” causes are less frequent, they carry good prognosis with prompt treatment of the underlying condition. Thus the evaluation for all potentially reversible conditions which cause dementia syndrome is the first most important step in the assessment of dementia syndrome and this is essential in all cases presenting with features of dmentia. The type of investigations can be decided based on the clinical features and context of care. This aspect is discussed in detail in the 2009 Dementia Supplement of Indian Journal of Psychiatry. Clinical Assessment Patients who seek help in clinical settings often do not represent cases prevalent in the community. Reversible causes thus may be much more common in clinical settings than in community settings. Routine investigations should include complete blood count, erythrocyte sedimentation rate, and serum/blood levels of urea, electrolytes, calcium and phosphate, liver, renal and, thyroid function tests, urine analysis, VDRL and Serum B12, and Folate levels. CT scan or MRI scan, at times, can be a very useful investigation in the differential diagnosis of dementia. Investigations for testing the HIV status, ECG, Chest radiograph, Electroencephalogram, Neuropsychological assessment etc are investigations worth considering. Common Potentially Reversible Causes Depression Medication Induced (Especially drugs with anticholinergic activity) Metabolic derangements Thyroid disorders (Hyopthyroidism is a common cause) Vitamin B12 deficiency Thiamine deficiency Chronic disease (e.g., renal failure, hepatic failure, malignancy) Gastrointestinal disorders Whipple's disease Vitamin E deficiency Pellagra Structural brain lesions Subdural hematoma Normal pressure hydrocephalus Tumor Infections Neurosyphilis HIV/AIDS How to investigate and rule out Reversible causes? A reliable, detailed history will guide us in identifying the causes of dementia. We have to rule out common reversible causes and the eminently reversible causes first. See table-5 for the list. Investigations to rule out less common causes may be needed when the clinical features indicate a high index of suspicion of reversible dementia.Table 5: Common Subtypes of Irreversible DementiasDementia syndrome is linked to many underlying causes and diseases of the brain. The most common causes accounting for vast majority of cases are due to Alzheimer's disease, Vascular dementia, Dementia with Lewy Bodies and Fronto-temporal dementia. Please follow the steps described in Figures 1, 2, 3 and 4 for systematic evaluation of a person presenting with cognitive symptomsFigure 1: Initial assessmentFigure 2: Clinical Assessment: Step 1Figure 3: STEP 2: Evaluate Cognitive ImpairmentFigure 4: STEP 3 Evaluation after recognition of the syndrome of dementia look for medical problemsCognitive assessment can be made as part of detailed examination of higher functions. Commonly used instruments like Mini-Mental State Examination (MMSE) can be used. Addenbrooke's Cognitive Examination (ACE) is a more detailed test battery for assessing cognitive functions. Assessment of the activities of daily living is very important. This information is essential in formulating the individualized plan of intervention. Everyday Activities Scale for India (EASI) developed during the Indo-US Cross-National Dementia Epidemiology Study is useful for this purpose, especially in the rural illiterate. Use of simple instruments like the Clinical Dementia Rating Scale can help in assessing the severity of dementia in routine clinical practice. Assessment of non-cognitive symptoms like Behavioural and Psychological Symptoms of Dementia (BPSD) is yet another important part of clinical assessment. Two commonly used scales for assessment of these symptoms are the Neuropsychiatric Inventory (NPI) and the BEHAVE-AD Both these scales use the caregiver interview for rating behavioural symptoms. Knowledge of instruments like MMSE, ACE, EASI, Behave-AD and NPI is helpful in the detailed and effective assessments of patients with dementia. Clinical Criteria for Diagnosis of Dementia ICD- 10 clinical criteria may be used for diagnosis of Dementia and subtyping. Alterantively one could use the DSM-5 criteria too. Since ICD 10 does not give criteria for Dementia with Lewy Bodies, one could instead rely on the Consensus criteria or the DSM-5 criteria. You may use the consensus clinical diagnostic criteria. After detailed assessment usually, the clinician would be in a position to judge the cause of the dementing illness. However at times, even the distinction between Vascular Dementia and Alzheimer's Disease (AD) may appear difficult. Clinical recognition of the subtypes of dementia is important and is easier during the early part of the illness. The differentiation between Lewy Body Dementia (LBD), Frontotemporal Dementia (FTD) and AD can be attempted during the initial evaluations itself. Such differentiation is feasible in clinical practice by using clinical criteria for these subtypes. The clinicians might choose any standard criteria for making clinical diagnosis of dementia, especially common sub-types. See Table 6 for the criteria which may be useful in clinical practiceTable 6: Diagnostic criteria for DementiaICD 10 – DEMENTIA G1. Evidence of each of the following: (1) A decline in memory, which is most evident in the learning of new information, although in more severe cases, the recall of previously learned information may be also affected. The impairment applies to both verbal and non-verbal material. The decline should be objectively verified by obtaining a reliable history from an informant, supplemented, if possible, by neuropsychological tests or quantified cognitive assessments. The severity of the decline, with mild impairment as the threshold for diagnosis, should be assessed as follows: Mild: a degree of memory loss sufficient to interfere with everyday activities, though not so severe as to be incompatible with independent living. The main function affected is the learning of new material. For example, the individual has difficulty in registering, storing and recalling elements in daily living, such as where belongings have been put, social arrangements, or information recently imparted by family members. Moderate: A degree of memory loss which represents a serious handicap to independent living. Only highly learned or very familiar material is retained. New information is retained only occasionally and very briefly. The individual is unable to recall basic information about where he lives, what he has recently been doing, or the names of familiar persons. Severe: a degree of memory loss characterized by the complete inability to retain new information. Only fragments of previously learned information remain. The subject fails to recognize even close relatives. (2) A decline in other cognitive abilities characterized by deterioration in judgement and thinking, such as planning and organizing, and in the general processing of information. Evidence for this should be obtained when possible from interviewing an informant, supplemented, if possible, by neuropsychological tests or quantified objective assessments. Deterioration from a previously higher level of performance should be established. The severity of the decline, with mild impairment as the threshold for diagnosis, should be assessed as follows: Mild. The decline in cognitive abilities causes impaired performance in daily living, but not to a degree making the individual dependent on others. More complicated daily tasks or recreational activities cannot be undertaken. Moderate. The decline in cognitive abilities makes the individual unable to function without the assistance of another in daily living, including shopping and handling money. Within the home, only simple chores are preserved. Activities are increasingly restricted and poorly sustained. Severe. The decline is characterized by an absence, or virtual absence, of intelligible ideation. The overall severity of the dementia is best expressed as the level of decline in memory or other cognitiveabilities, whichever is the more severe (e.g. mild decline in memory and moderate decline in cognitive abilitiesindicate a dementia of moderate severity). G2. Preserved awarenenss of the environment (i.e. absence of clouding of consciousness (as defined in F05, criterion A)) during a period of time long enough to enable the unequivocal demonstration of G1. When there are superimposed episodes of delirium the diagnosis of dementia should be deferred. G3. A decline in emotional control or motivation, or a change in social behaviour, manifest as at least one of the following: emotional lability; irritability; apathy; coarsening of social behaviour. G4. For a confident clinical diagnosis, G1 should have been present for at least six months; if the period since the manifest onset is shorter, the diagnosis can only be tentative. Comments: The diagnosis is further supported by evidence of damage to other higher cortical functions, such as aphasia, agnosia, apraxia. Judgment about independent living or the development of dependence (upon others) need to take account of the cultural expectation and context. Dementia is specified here as having a minimum duration of six months to avoid confusion with reversible states with identical behavioural syndromes, such as traumatic subdural haemorrhage (S06.5), normal pressure hydrocephalus (G91.2) and diffuse or focal brain injury (S06.2 and S06.3). ICD 10 F00 DEMENTIA IN ALZHEIMER'S DISEASE The general criteria for dementia (G1 to G4) must be met. There is no evidence from the history, physical examination or special investigations for any other possible cause of dementia (e.g. cerebrovascular disease, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus), a sysytemic disorder (e.g. hypothyroidism, vit. B12 or folic acid deficiency, hypercalcaemia), or alcohol- or drug-abuse. Comments: The diagnosis is confirmed by post mortem evidence of neurofibrillary tangles and neuritic plaques in excess of those found in normal ageing of the brain. The following features support the diagnosis, but are not necessary elements: Involvement of cortical functions as evidenced by aphasia, agnosia or apraxia; decrease of motivation and drive, leading to apathy and lack of spontaneity; irritability and disinhibition of social behaviour; evidence from special investigations that there is cerebral atrophy, particularly if this can be shown to be increasing over time. In severe cases there may be Parkinson-like extrapyramidal changes, logoclonia, and epileptic fits. Specification of features for possible subtypes. Because of the possibility that subtypes exist, it is recommended that the following characteristics be ascertained as a basis for a further classification: age at onset; rate of progression; the configuration of the clinical features, particularly the relative prominence (or lack) of temporal, parietal or frontal lobe signs; any neuropathological or neurochemical abnormalities, and their pattern. The division of AD into subtypes can at present be accomplished in two ways: first by taking only the age of onset and labeling AD as either early or late, with an approximate cut-off point at 65 years ICD 10 F01 VASCULAR DEMENTIA G1. The general criteria for dementia (G1 to G4) must be met. G2. Unequal distribution of deficits in higher cognitive functions, with some affected and others relatively spared. Thus memory may be quite markedly affected while thinking, reasoning and information processing may show only mild decline. G3. There is clinical evidence of focal brain damage, manifest as at least one of the following: unilateral spastic weakness of the limbs; unilaterally increased tendon reflexes; an extensor plantar response; pseudobulbar palsy. G4. There is evidence from the history, examination, or tests, of a significant cerebrovascular disease, which may reasonably be judged to be etiologically related to the dementia (e.g. a history of stroke; evidence of cerebral infarction). Consensus criteria for FRONTOTEMPORAL DEMENTIA Core diagnostic features Insidious onset and gradual progression Early decline in social interpersonal conduct Early impairment in regulation of personal conduct Early emotional blunting Early loss of insight Supportive diagnostic features Behavioral disorder Decline in personal hygiene and grooming Mental rigidity and inflexibility Distractibility and impersistence Hyperorality and dietary changes Perseverative and stereotyped behavior Utilization behavior Speech and language Altered speech output Aspontaneity and economy of speech Pressure of speech Stereotypy of speech Echolalia Perseveration Mutism Physical signs Primitive reflexes Incontinence Akinesia, rigidity, and tremor Low and labile blood pressure Investigations Neuropsychology: impairment on frontal lobe tests without severe amnesia, aphasia, or perceptuospatial disorder Electroencephalography: normal on conventional EEG despite clinically evident dementia Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality Revised criteria for the clinical diagnosis of probable and possible dementia with Lewy bodies (DLB) Essential for a diagnosis of DLB is dementia, defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention, executive function, and visuoperceptual ability may be especially prominent and occur early. Core clinical features (The first 3 typically occur early and may persist throughout the course.) Fluctuating cognition with pronounced variations in attention and alertness. Recurrent visual hallucinations that are typically well formed and detailed. REM sleep behavior disorder, which may precede cognitive decline. One or more spontaneous cardinal features of parkinsonism: these are bradykinesia (defined as slowness of movement and decrement in amplitude or speed), rest tremor, or rigidity. Supportive clinical features Severe sensitivity to antipsychotic agents postural instability; repeated falls; syncope or other transient episodes of unresponsiveness; severe autonomic dysfunction, e.g., constipation, orthostatic hypotension, urinary incontinence; hypersomnia; hyposmia; hallucinations in other modalities; systematize