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Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
Psychiatric Manifestations In Dementia
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Psychiatric Manifestations In Dementia

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

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