Psychiatric Manifestations In Dementia

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Psychiatric Manifestations In Dementia

  1. 1. PSYCHIATRIC MANIFESTATIONS IN DEMENTIA
  2. 2. Introduction <ul><li>Neuropsychiatric symptoms are a common feature of all neurodegenerative dementias. </li></ul><ul><li>They are often more disturbing to the caregivers than cognitive decline. </li></ul><ul><li>Leading cause for hospitalization, residential placement, and/or psychopharmacologic therapy. </li></ul><ul><li>Major contributors to the emotional, social, and economic burden of dementia. </li></ul><ul><li>Very distressing to patients and should be promptly recognized and treated. </li></ul>
  3. 3. Definitions <ul><li>Aberrant motor behaviour: Excessive motor activity such as pacing, wandering, fidgeting, hand-wringing, inability to sit still etc. </li></ul><ul><li>Agitation: Excessive motor activity associated with feeling of inner tension. </li></ul><ul><li>Anxiety: Excessive and unjustified apprehension, feeling of foreboding, and thoughts of impending doom. </li></ul><ul><li>Apathy: Lack of motivation and diminished goal-directed behaviour, reduced goal-directed cognition and decreased emotional engagement. </li></ul>
  4. 4. Definitions <ul><li>Delusions: False beliefs based on incorrect references about external reality that are firmly held despite evidence to the contrary. </li></ul><ul><li>Depression: Sadness, inability to feel pleasure, feelings and thoughts of worthlessness, hopelessness, helplessness or guilt; recurrent thoughts of death, fatigue </li></ul><ul><li>Disinhibition: Inappropriate social and interpersonal conduct, tactlessness, impulsivity. </li></ul><ul><li>Euphoria: elevated mood with excessive happiness and overconfidence without the elevated mental and motor rate of mania. </li></ul>
  5. 5. Definitions <ul><li>Hallucinations: sensory perceptions with compelling sense of reality but without concomitant stimulation of the relevant sensory organ. </li></ul><ul><li>Illusions: Misinterpretation of visual stimuli from distorted perception. </li></ul><ul><li>Irritability: susceptibility to easily provoked anger or annoyance. </li></ul><ul><li>Obsessive compulsive behavior: Recurrent thoughts, repetitive acts, or compulsive purposeless behavior. </li></ul>
  6. 6. Mild Cognitive Impairment <ul><li>Heterogeneous intermediate state that falls between normal cognitive aging and dementia. </li></ul><ul><li>Risk factor for future cognitive decline. </li></ul><ul><li>Annual rates of conversion of MCI to dementia: 10% to 15% ( 2% to 3% in cognitively normal elderly persons). (Petersen et al, 2001) </li></ul><ul><li>Neuropsychiatric symptoms are common. </li></ul><ul><li>Using the Neuropsychiatric Inventory (NPI) 43% of patients with MCI in a community sample and 75% of patients seen at a tertiary health care center have at least one behavioral symptom. </li></ul>
  7. 7. Mild Cognitive Impairment <ul><li>Highest prevalence: depression, apathy, irritability, anxiety, and agitation. </li></ul><ul><li>Rare: Psychotic symptoms, euphoria, and disinhibition. </li></ul><ul><li>Presence and severity of neuropsychiatric symptoms correlate with the degree of cognitive and functional impairment. </li></ul><ul><li>32% of the nondepressed but 85% of the depressed amnestic MCI patients convert to Alzheimer's dementia over 5 years. (RR 2.6, 95% CI 1.8 to 3.6). </li></ul>
  8. 8. Alzheimer's Disease- Apathy <ul><li>Commonest type of dementia in the elderly. </li></ul><ul><li>Numerous neuropsychiatric symptoms. </li></ul><ul><li>Worsen over the course of the disease; symptoms may fluctuate (Cummings, 2000b). </li></ul><ul><li>Apathy is the most pervasive neuropsychiatric symptom (42% of patients with mild, 80% with moderate, 92% with advanced AD) (Mega et al, 1996). </li></ul><ul><li>Renders patients more dependant and adds to caregiver burden (Cummings, 2003). </li></ul>
  9. 9. Alzheimer's Disease- Apathy <ul><li>Reflects fronto- subcortical dysfunction and disconnection of the anterior cingulate cortex from other cortical and subcortical areas. </li></ul><ul><li>Loss of interest in previously enjoyed activities, like hobbies, social outings, spending time with relatives, aloofness, reduced spontaneity, emotional behavior and motivation. </li></ul><ul><li>Apathy is associated with executive decline. </li></ul><ul><li>Apathy and depression commonly co-occur, but are not synonymous with each other (Cummings, 2003). </li></ul>
  10. 10. Alzheimer's Disease- Anxiety <ul><li>Another early feature of AD. </li></ul><ul><li>Prevalence: </li></ul><ul><ul><li>Cognitively normal elderly- 6% (Lyketsos et al, 2002) </li></ul></ul><ul><ul><li>MCI -10% to 25% </li></ul></ul><ul><ul><li>AD- 50% (Hwang et al, 2004; Lyketsos et al, 2002). </li></ul></ul><ul><li>Triggers: </li></ul><ul><ul><li>Subjective awareness of his or her cognitive decline </li></ul></ul><ul><ul><li>Increased dependency on others </li></ul></ul><ul><ul><li>Fear of the disease and the future </li></ul></ul><ul><ul><li>Fear of abandonment by the caregiver </li></ul></ul><ul><ul><li>Changes in the daily routine or environment. </li></ul></ul>
  11. 11. Alzheimer's Disease- Agitation <ul><li>Agitation and irritability frequently co-occur. </li></ul><ul><li>They may begin in the MCI phase and progress throughout the course. </li></ul><ul><li>More common in: males, patients with later onset of dementia, and patients of more advanced age. </li></ul><ul><li>Disruptive, aggressive, and/or resistive behaviors and is related to changes in frontal cortex (Cummings, 2003). </li></ul><ul><li>Difficulties in understanding the actions or words of others may lead to high levels of frustration. </li></ul><ul><li>Inability to complete tasks completed with ease in the past or a feeling of being mistreated/ ignored. </li></ul>
  12. 12. Alzheimer's Disease- Depression <ul><li>Very common in AD (10% of mild, 40% to 60% of moderate, and 60% or more of severe AD). </li></ul><ul><li>Rarely severe to merit diagnosis of major depressive disorder. </li></ul><ul><li>Usually represent the less severe dysphoria/ minor depression. </li></ul><ul><li>Risk factors: </li></ul><ul><ul><li>Family or personal history of depressive disorder </li></ul></ul><ul><ul><li>Female gender, </li></ul></ul><ul><ul><li>Younger age. </li></ul></ul>
  13. 13. Alzheimer's Disease- Depression <ul><li>Depressive symptoms are associated with: </li></ul><ul><ul><li>Decreased quality of life </li></ul></ul><ul><ul><li>Functional dependency </li></ul></ul><ul><ul><li>Increased institutionalization </li></ul></ul><ul><ul><li>Caregiver burden </li></ul></ul><ul><ul><li>Caregiver depression </li></ul></ul><ul><li>New-onset depression in elderly persons may indicate the presence of dementia. </li></ul><ul><li>Predicts cognitive decline </li></ul><ul><li>In MCI, it increases risk of developing AD </li></ul>
  14. 14. Alzheimer's Disease- Psychosis <ul><li>Medication or delirium induced or, in the case of visual hallucinations, triggered by poor visual acuity. </li></ul><ul><li>Usually in the moderate and advanced stages of AD. </li></ul><ul><li>Hallucinations: 10% to 20% of patients, usually visual. </li></ul><ul><li>Delusions: 30% - 50% of patients, more in the later stgs. </li></ul><ul><li>Most common themes: infidelity, theft, and paranoia. </li></ul><ul><li>Female gender- risk factor for psychosis in AD </li></ul><ul><li>Living with a spouse is protective. </li></ul><ul><li>Patients with delusions have more dysfunction of frontal and temporal regions than those without. (Cummings, 2003). </li></ul>
  15. 15. Prevalence of neuropsychiatric symptoms in MCI and AD 4 15 3 15 <1 10 20 11 1 3 MCI (n=320) Community Study % Tertiary Care Centre study % 27 14 16 Aberrant motor behaviour 38 29 27 Irritability 21 18 13 Disinhibition 51 39 27 Apathy 8 11 3 Euphoria 35 25 22 Anxiety 50 39 32 Dysphoria 34 18 30 Agitation 6 0 11 Hallucination 26 4 18 Delusion AD (n=124) MCI (n=28) AD (n=362) Symptom
  16. 16. Alzheimer's Disease Variants <ul><li>Frontal variant of AD: additional prominent executive dysfunction and frontal-type behaviors (impulsivity, disinhibition, agitation, euphoria, and compulsive behaviors (ie, hoarding) (Cummings, 2000b; Cummings,2003). </li></ul><ul><li>Early-onset AD , esp, autosomal dominant forms (mutations of APP gene, presenilin-1 gene, presenilin-2 gene) frequently display increased and atypical psychopathology. </li></ul><ul><li>Emotional lability, OCDs, symptoms of frontal variant FTD, and of the Kluver-Bucy syndrome. </li></ul>
  17. 17. Dementia With Lewy Bodies <ul><li>2nd most common neurodegenerative dementia of elderly. </li></ul><ul><li>Neuropsychiatric evaluation is crucial as visual hallucinations are a core diagnostic criterion and delusions and prominent early depression are supportive features (McKeith et al, 2005). </li></ul><ul><li>Upto 98% of patients experience some neuropsychiatric symptoms in the course of their illness. </li></ul>
  18. 18. Dementia With Lewy Bodies <ul><li>These symptoms, along with cognitive fluctuations and extrapyramidal symptoms, differentiate DLB from other common types of dementia. (Apostolova and Cummings, 2005). </li></ul><ul><li>Psychotic symptoms are very common in both the pure and the common form of DLBD. </li></ul><ul><li>Pesenting feature in 14% of patients with common and 18% with pure DLB. </li></ul>
  19. 19. Dementia With Lewy Bodies <ul><li>Visual hallucinations: </li></ul><ul><li>In the early disease stages when cognitive symptoms are still mild, hallucinations are seen with much greater frequency in DLB relative to AD. </li></ul><ul><li>Of patients with mild dementia (MMSE> 20) with visual hallucinations, 93% meet pathologic criteria for DLB on autopsy (Apostolova and Cummings, 2005). </li></ul><ul><li>In DLB, other dementias they are brightly colored 3-D representations of people and animals. </li></ul>
  20. 20. Dementia With Lewy Bodies <ul><li>Frequently animated, may speak or make noise (ie, co-occur with auditory hallucinations). </li></ul><ul><li>Sometimes more pronounced in the evening when lack of strong sensory stimulation and solitude promote their appearance (Apostolova and Cummings, 2005; Ballard et al, 1997) </li></ul><ul><li>Depression: recently added supportive diagnostic criterion </li></ul><ul><li>Major depression is more common in DLB vs AD (16:1) </li></ul>
  21. 21. Dementia With Lewy Bodies <ul><li>Delusions: common in DLB and comprise a supportive diagnostic criterion (McKeith et al, 2005). </li></ul><ul><li>More common and more persistent in DLB than in AD. </li></ul><ul><li>Common themes: delusional misidentifications, paranoia, delusions of theft, abandonment, infidelity, or phantom boarder. </li></ul><ul><li>Delusional misidentifications: 33% of patients with DLB. Mistaking TV images for real, Capgras-like syndrome, Foley's syndrome, and reduplicative paramnesia. </li></ul>
  22. 22. Delusional misidentification syndromes <ul><li>Capgras syndrome: others are replaced by imposters. </li></ul><ul><li>Fregoli syndrome: strangers arent who they claim to be. </li></ul><ul><li>Intermetamorphosis: 2 people have exchanged their appearances. </li></ul><ul><li>Foley’s syndrome: one’s image belongs to another. </li></ul><ul><li>Doppelganger/ heautoscopy: one has a double. </li></ul><ul><li>Autoscopy: one’s body is a duplicate of the real body. </li></ul><ul><li>Reduplicative paramnesia: one’s home (or other location) has been duplicated. </li></ul><ul><li>Reduplication for time: there are 2 parallel chronologic time points and one exists indepedently in both of them. </li></ul>
  23. 23. Dementia With Lewy Bodies <ul><li>Differentiating DLB from AD on the basis of clinical features is challenging. </li></ul><ul><li>A recent study concluded that only visual hallucinations and visuospatial dysfunction contributed to a more accurate diagnosis of pathologically proven DLB. </li></ul><ul><li>Visual hallucinations were the most specific (specificity 99%), and lack of visuospatial impairment had the highest negative predictive value (NPV 83%). </li></ul><ul><li>Extrapyramidal signs were not helpful in the study sample (Tiraboschi et al, 2006). </li></ul>
  24. 24. Frontotemporal Dementia <ul><li>3 subtypes: frontal or behavioral FTD (fvFTD), primary progressive aphasia (PPA), and semantic dementia (SD). </li></ul><ul><li>PPA and FTD: onset at 45 to 60 yrs, while SD: at 70 yrs. </li></ul><ul><li>fvFTD: insidious relentless disorder with early prominent behavioral and personality disturbances. </li></ul><ul><li>Impulsivity, tactless conduct, antisocial trends, disinhibition, lack of concern with social norms, loss of interpersonal boundaries, apathy, self-centeredness, and lack of empathy are hallmark features. </li></ul><ul><li>OCDs and stereotyped behaviors also are common. </li></ul>
  25. 25. Frontotemporal Dementia <ul><li>PPA: expressive language impairments, halted speech, and frequent phonemic paraphasic errors. </li></ul><ul><li>SD: fluent but impoverished speech resulting from progressive loss of semantic knowledge, difficulty reading irregular words (eg, pint) and frequent literal paraphasias of the supraordinate type. </li></ul><ul><li>Both disorders ultimately lead to mutism. </li></ul><ul><li>Neuropsychiatric symptoms are the exception in PPA. </li></ul><ul><li>Behavioral abnormalities are sometimes prominent in SD; they tend to resemble those seen in fvFTD </li></ul>
  26. 26. Vascular Dementia <ul><li>The most common neuropsychiatric symptom is depression , which is due to disruption in fronto-subcortical circuitry and related brain regions. </li></ul><ul><li>New-onset depression has been shown to correlate with white matter hyperintensities, HTN, and CAD. </li></ul><ul><li>Poststroke depression contributes significantly toward short-term functional disability (Alexopoulos et al, 1997). </li></ul><ul><li>Other neuropsychiatric features: delusions in 12.5% and hallucinations in 15.5% of the patients, aggression, apathy, irritability, and anxiety (Lyketsos et al, 2000). </li></ul>
  27. 27. Evaluation Of Neuropsychiatric Symptoms In Demented Patients <ul><li>Detailed history about the patient's cognitive baseline and any new symptoms is of utmost importance. </li></ul><ul><li>A thorough review may reveal the presence of infection, dehydration, starvation, or intoxication. </li></ul><ul><li>A comprehensive medical, neurologic, and psychiatric bedside examination is mandatory. </li></ul>
  28. 28. Evaluation Of Neuropsychiatric Symptoms In Demented Patients <ul><li>All concurrent medical problems with special attention to decompensation of a chronic condition. </li></ul><ul><li>Review of recent and current medications, drug interactions and side effects, and substance withdrawal. </li></ul><ul><li>A detailed social and environmental history is required. </li></ul><ul><li>Significant noise exposure, over- or understimulation, overcrowding, change of environment or routine can trigger abnormal neuropsychiatric behaviors. </li></ul><ul><li>Laboratory studies or brain imaging. </li></ul>
  29. 29. Behavioral Interventions <ul><li>Most important intervention is family and caregiver education about the disease and all possible cognitive and neuropsychiatric complications. </li></ul><ul><li>Done at the time of diagnosis or shortly thereafter. </li></ul><ul><li>Will help mitigate the caregiver's resentment, guilt, anger, retaliation, and apprehension. </li></ul><ul><li>The family and caregivers need to be referred to appropriate support groups. </li></ul><ul><li>Behavioral interventions are the first line of therapy for many neuropsychiatric problems. </li></ul>
  30. 30. Behavioral Interventions <ul><li>Apathy: stimulating activities. </li></ul><ul><li>Anxiety: reassurance, avoidance of anxiety-provoking situations, teaching of coping strategies. </li></ul><ul><li>Agitation: calm and nonconfrontational reassurance and redirection. </li></ul><ul><li>Visual hallucinations: occurring in the evenings may be due to sensory understimulation and may resolve with measures such as leaving a light or soft music on. </li></ul><ul><li>Orientation: Calendar, a clock, and family photographs. </li></ul>
  31. 31. Pharmacologic Interventions: Cholinesterase inhibitors <ul><li>Mainstream cognitive therapy for AD, DLBD and VaD. </li></ul><ul><li>Also provide a reduction of neuropsychiatric symptoms. </li></ul><ul><li>Donepezil and rivastigmine: decrease neuropsychiatric symptomatology in patients with AD. </li></ul><ul><li>The greatest impact of AChEIs has been on apathy and mood symptoms. </li></ul><ul><li>To be used alone or in conjunction with medications from other classes for cognitive and neuropsychiatric symptoms </li></ul>
  32. 32. Memantine <ul><li>Newest agent approved for treatment of AD. </li></ul><ul><li>N-methyl-d-aspartate receptor agonist. </li></ul><ul><li>Improves cognitive and functional performance in moderate to severe AD. </li></ul><ul><li>A recent study of AD patients reported improvement of agitation, aggression, irritability, and lability compared with placebo (Cummings et al, 2006). </li></ul>
  33. 33. Antipsychotics <ul><li>Agression: Risperidone (0.5 mg to 2.0 mg/d) and olanzapine (5 mg to 10 mg/d) are effective (in AD). </li></ul><ul><li>Psychotic symptoms: Risperidone (1 mg/d) and Aripiprazole (2.0 mg to 25 mg/d), </li></ul><ul><li>Anxiety and Euphoria: Olanzapine (5 mg to 10 mg/d). </li></ul><ul><li>Agitation: atypical antipsychotics. </li></ul><ul><li>However, significantly more side effects were reported relative to placebo. </li></ul><ul><li>These included CVAs, death, EPS, falls, drowsiness, peripheral edema, and abnormal gait. </li></ul>
  34. 34. Antipsychotics <ul><li>Typical antipsychotics have been largely replaced by the atypical antipsychotics in dementia. </li></ul><ul><li>Supporting evidence is limited, while some side effects (eg, sedation and EPS) are more severe (Sink et al, 2005). </li></ul><ul><li>Typical antipsychotics- contraindicated in DLB as they may cause severe adverse events, such as NMS, death. </li></ul><ul><li>The frequency of extrapyramidal adverse events is much higher in DLB versus AD (81% versus 19%). </li></ul><ul><li>Atypical antipsychotics are generally safer and preferred in DLB. </li></ul>
  35. 35. Mood Stabilizers <ul><li>Valproic acid and carbamazepine have been tested for the treatment of behavioral problems in dementia. </li></ul><ul><li>Neither drug is was shown to be effective (Sink et al, 2005). </li></ul><ul><li>Should be regarded as second-line therapies for the treatment of agitation in dementia. </li></ul>Antidepressants <ul><li>SSRIs: well tolerated, but only modestly effective for the management of behavioral problems in dementia. </li></ul><ul><li>They may also help reduce anxiety, agitation, and emotional lability (Sink et al, 2005). </li></ul>
  36. 36. Pharmacotherapy of neuropsychiatric symptoms Risperidone + SSRIs/SNRIs Trazodone AChEIs SSRIs, SNRIs, BZDs SSRIs Risperidone, Quetiapine SSRIs Quetiapine, Risperidone First line Olanzepine+SSRIs/SNRIs Psychotic depression Zolpidem Insomnia/ sundowning Apathy Atypical antipsychotics Anxiety SNRIs Depression Olanzapine, Aripiprazole Aggression Quetiapine, Risperidone Agitation Olanzapine, Aripiprazole Psychosis Second line Symptom
  37. 37. Conclusion <ul><li>Neuropsychiatric symptomatology is inherent in almost all neurodegenerative disorders. </li></ul><ul><li>In the initial stages of AD the primary concerns of patients and their families is on loss of memory. </li></ul><ul><li>Later, behavioral problems increasingly capture the attention of the relatives and health care professionals and require timely management. </li></ul><ul><li>Prevention, education, and adequate treatment of neuropsychiatric symptoms are the current standard of care of patients who are demented. </li></ul>
  38. 38. Key Points <ul><li>Neuropsychiatric symptoms are a common feature of all neurodegenerative dementias. </li></ul><ul><li>Neuropsychiatric disturbances are major contributors to the emotional, social, and economic burden of dementia. </li></ul><ul><li>The presence and severity of neuropsychiatric symptoms in MCI correlate with the degree of cognitive and functional impairment. </li></ul><ul><li>Behavioral symptoms, once manifest, tend to worsen over the course of Alzheimer's disease; symptoms may fluctuate and not be present at each clinical evaluation. </li></ul>
  39. 39. Key Points <ul><li>Apathy: most pervasive neuropsychiatric symptom in AD. </li></ul><ul><li>Anxiety: could be triggered by patient's awareness of the cognitive decline, increased dependency on others, and fear of the disease and the future. </li></ul><ul><li>Agitation: is related to changes in frontal cortex. </li></ul><ul><li>Depression: associated with decreased quality of life, functional dependency, increased institutionalization, caregiver burden, and caregiver depression. </li></ul><ul><li>New-onset depression in elderly persons may indicate the presence of dementia and predict cognitive decline. </li></ul>
  40. 40. Key Points <ul><li>Autosomal dominant forms of AD frequently display increased and atypical psychopathology. </li></ul><ul><li>Visual hallucinations are core diagnostic criteria for DLBD. </li></ul><ul><li>Neuropsychiatric symptoms differentiate DLBD from other common types of dementia. </li></ul><ul><li>Depression has been recently added as a supportive diagnostic criterion for the diagnosis of DLBD. </li></ul><ul><li>Visual hallucinations and visuospatial dysfunction contribute to a more accurate diagnosis of DLBD. </li></ul>
  41. 41. Key Points <ul><li>Frontal or behavioral FTD manifests with early prominent behavioral disturbances and personality changes. </li></ul><ul><li>Behavioral abnormalities in semantic dementia tend to resemble those seen in frontal or behavioral FTD. </li></ul><ul><li>The most common neuropsychiatric symptom seen in vascular dementia is depression. </li></ul><ul><li>Depression, aggressive behavior, apathy, irritability, and anxiety are the most common neuropsychiatric abnormalities in vascular dementia. </li></ul>
  42. 42. Key Points <ul><li>For patients with dementia, the most important intervention is family and caregiver education about the disease and all possible cognitive and neuropsychiatric complications. </li></ul><ul><li>B ehavioral interventions are the first line of therapy. </li></ul><ul><li>AChEIs: to be used either alone or in conjunction with medications from other classes for both cognitive and neuropsychiatric symptoms in dementia. </li></ul><ul><li>Typical antipsychotics are contraindicated in DLBD. </li></ul>

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