Behavior and psychological symptoms of dementia

1. Behavior and psychological symptoms of dementia

2. 為了與 「認知功能障礙」( cognitive impairment) 區分，Rabins 〈 1994 〉認為，應該把這些情緒、行為症狀歸類為「非認知症狀」( non-cognitive Symptoms)。 • 但非認知行為症狀有些卻是續發於認知功能障礙，例如：錯認、漫遊迷失等。 • 精神表現( psychiatric manifestation ) • 行為障礙( behavioral disturbance) (Rabins, 1996) • 1996, IPA 將這些症狀統稱為失智症的行為及心理症狀 ( Behavioral and psychological symptoms of dementia, BPSD) • 11.7 % ~ 70.6% AD p’t reveal non-cognitive symptoms (Ballard & Oyebode, 1995) • 主要分為五大類症狀：情感症狀、精神病症狀、驅力症狀、行為表現、其他（易怒、淡漠、去抑制化） • 焦慮、易怒及行為問題則多伴隨著認知功能退化而更嚴重。

3. Affective : depression : 0-31 % , euphoria, anxiety • Depression history (Rovner, 1989) • Family history (Pearlson, 1990; Lyketsos, 1996) • Young onset age (Rovner, 1989) • Female (Migliorelli, 1995) • Frequently occurring in early stage • Delusion : 40 %, delusion of theft 13-28% • Delusion frequently happen in mild to moderate stage (2-4 y), particular on moderate stage. • Severe dementia delusions are rare. (Deutsch, 1991) • Cummings (1985), limbic system and temporal lobe change are played important role. • Misidentification : 30-55 %, more of [somebody in my house ]. • Hallucination : 7-49 %, most of visual hallucination • Apathy (80 %) : correlation to frontal and temporal lobe blood flow  (Craig, 1996)

4. Sleep disturbances (more) : 42 % (Reisberg, 1987) • Agitation • Irritability • Aggression (more) : 20-30 % (Burns, 1990; Deutsch, 1991) • Disinhibition: inadequate behavior (rare) • Aberrant behavior: • hoarding (rare) ((2%), Homma, Ishii & Niina, 1994), • repetitive behaviors (more) : more found in moderate stage relation to frontal lobe functions. • Hypersexuality: relation to frontal and temporal area. • Hyperphagia : 5-26%, relation to memory impairment or hypothalamus. • Wander and loss way (more) : 18 %, (Burns, 1990), more found in moderate stage.

5. NPI study • Mega, 1996. • Apathy (72 %) • Agitation (60 %) • Anxiety (48 %) • Irritation (42 %) • Depression (38 %) • Aberrant behavior (38 %)

10. Rubin, E. H.. (1990): Psychopathology of Senile Dementia of the Alzheimer Type. Advances in Neurology, Vol. 51: Alzheimer’s disease. • 83 controls and 68 CDR 1 subjects • Longitudinal and cross-sectional method • Factor analysis of the 11 personality items of the Blessed Dementia Scale  six categories • Passive change (insecure-inactive, less cheerful, less responsive) • Agitated changes (irritable, hyperactive) • Self-centered changes

11. Behavioral Changes • 41 subjects with CDR 0.5 show that about two-thirds of subjects • demonstrate one or more of these behavioral changes.

12. Depressive Symptoms in SDAT subjectsFeighner symptoms of depression

13. Psychotic Symptoms 1. ½ subjects with SDAT during the course of the illness, most common in mild to moderate stage, particular on moderate stage. (twice) 2. Visual hallucination were most common. 3. CDR 0.5 the psychotic symptoms were rare. 4. Mild stage had occurred psychotic symptoms the cognitively deteriorated more rapidly than non, 15 month later assessment 80 % (EP) vs. 33 % (NP).

14. Discussion • Behavioral changes are common: passive changes are present in mild stage, agitation increasing throughout the course, and self-centered behaviors peak during the moderate stage. • Behavioral changes occurring early do not predict a more rapid course. (relation to frontal lobe) • Major affective disorder is rare. • The changes in psychomotor activity, interest, concentration, and energy are more frequently report by the collateral source than subjects. • The psychotic symptoms most evident during the moderate stage. • Psychotic symptoms occurring during mild stage are associated with more rapid cognitive deterioration. (relation to temporal lobe) • CDR 0.5 indicate behavioral change and affective pattern that are more similar to mild stage than controls, but the psychotic symptoms are rare.

15. Depression vs. dementia • 兩者獨立診斷，且無相似症狀，診斷上沒有困難 • 兩者獨立診斷，只是有人隨機同時有兩種症狀 • 兩者為共同病因造成，如：巴金森氏症、血管性失智症、均易發生憂鬱症，也容易發生失智症 • 藥物所導致的認知功能減損 • 失智症病人的憂鬱症狀：過去認為是因為病人沒有辦法面對不斷失去的認知功能而感到傷痛，不過目前的研究已經證實應該是跟神經傳導物質或神經細胞的減少有關。 • 憂鬱症病人有認知功能衰退，以往會被稱為假性痴呆，不過現在的研究已經證實即使經過治療有一群人的認知功能是無法恢復的，他們的image也呈現出類似AD病人的影像。稱之為dementia syndrome of depression。 • Alexopoulos (1993) 研究發現，有假性痴呆的憂鬱症病人比單純憂鬱症的病人，前者有43%發展成不可逆的失智症，後者為12%，前者得到失智症的機會高出4.69倍。

16. Devanand (1996)，憂鬱情緒是失智症的重要危險因子。 • Y.I. Sheline, B.l. Mittler, M.A. Mintun. The hippocampus and depression. Eur Psychiatry 2002; 17 Suppl 3:300-5.

17. Core symptoms of depressions from the DSM-IV • Depressed mood, reports sadness or appears despondent • Markedly diminished interest or pleasure in activated • Significant weight loss or gain (5% of body weight in 1 month) or change in appetite. • Sleep disturbance: insomnia or hypersomnia. • Excessive or depressed level of activity. • Fatigue or low energy level • Feeling of guilt or worthlessness • Poor concentration and indecisiveness • Recurrent thoughts of death or suicide.

18. Mental status change Dysphoria Apathy Decreased motivation Anxiety Depressed affect Persecutory delusions Psychomotor retardation Impaired memory retrieval Poor wordlist generation Dilapidation of cognition (calculation, abstraction) Awareness of cognitive deficit Neurovegetative signs Sleep disturbance Loss of appetite and weight Constipation Impotence Motor : Bradykinesia Masked faces Stooped posture Slow, hypophonic speech Age > 60 Subacute onset and rapid progression of intellectual decline Past history of mood disorder Family history of mood disorder Enlarged lateral vertrivles J L Cummings and DF Benson, Dementia 1992. Major characteristics of the dementia syndrome of depression

19. Dementia are proteinopathies

20. Synucleinopathy • Parkinson disease • Dementia with Lewy bodies • Multiple system atrophy • Hallervorden-Spatz syndrom

21. Neuropsychiatric disturbances in PD

22. Neuropsychiatric disturbances in DLB

23. REM Sleep Behavior Disorder • A. Patient has a complaint of violent or injurious behavior during sleep. • B. Limb or body movement is associated with dream mentation. • C. At least one of the following occurs: 1. Harmful or potentially harmful sleep behaviors. 2. Dreams appear to be “acted out”. 3. Sleep behaviors disrupt sleep continuity. • D. Polysomnographic monitoring demonstrates at least one of following electrophysiologic measures during rapid eye movement (REM) sleep: 1. Excessive augmentation of chin electromyographic (EMG) tone. 2. Excessive chin or limb phasic EMG twitching, irrespective of chin EMG activity and one or more of the following clinical features during REM sleep: a. Excessive limb or body jerking. b. Complex, vigorous, or violent behaviors. c. Absent of epileptic activity in association with the disorder. • E. The symptoms are not associated with mental disorders but may be associated with neurologic disorders. • F. Other Sleep disorders (eg. Sleep terrors or sleepwalking) can be present but are not the cause of the behavior.

24. REM Sleep Behavior disorder in PD and DLB • 38 % 0f 29 patient with idiopathic RBD who subsequently developed a PD with a mean of 12.7 years after the onset of RBD. • 65% have developed parkinsonism and/or dementia during follow up. • 1995: the association of RBD and DLB • Even in the absent of visual hallucination of parkinsonism, the presentation of dementia and RBD may nevertheless indicate underlying Lewy body disease. • Many frequent finding in DLB is rapid eye movement (REM) sleep disorder.

25. Neuropsychiatric abnormalities in synucleinopathies • Prominent delusions • Hallucinations • REM sleep behavioral disorder

26. Other study about DLB

27. Tauopathies • Frontotemporal lobar degeneration • Progressive supranuclear palsy • Corticobasal degeneration

28. Frontal- subcortical systems • Executive dysfunction • Apathy • Disinhibition • Repetitive and compulsive behaviors with rituals • Hallucinations and sleep disturbances unusual

30. Frontal systems • Primary motor • Premotor • Frontal eye fields • Dorsolateral prefrontal • Orbital prefrontal • Anterior cingulate circuit BPSD, Mega and Cummings (1994)

32. Dorsolateral prefrontal • Poor organizational strategies • Poor memory search strategies • Stimulus-bound behavior/ environmental dependency • Impaired set shifting and maintenance • Verbal-manual dissociation

34. Orbital prefrontal • Personality change: Irritability, Tactlessness, Fatuous euphoria, Impulsivity, Undue familiarity • Environmental dependency: Utilization behavior, imitation behavior • Mood disorders: lability, mania • O.C.D (with increased orbitofrontal and caudate metabolism)

36. Anterior cingulate circuit • Impaired motivation: Akinetic mutism Marked apathy Psychiatry emptiness Poverty of spontaneous speech Indifference to pain • Poor response inhibition

37. Other study about corticobasal degeneration • Litvan I, Cummings J.L., Mega M. Neuropsychiatric features of corticobasal degeneration. J Neurol Neurosurg Psychiatry 1998; 65 : 717-721. • Depression (73%) • Apathy (40 %) • Irritability (20%) • Agitation (20%) • Anxiety, disinhibition, delusions or aberrant motor behavior were less. • Depression and irritability are more than PSP p’t. • PSP p’t are more apathy than CBD p’t. • The findings indicate that frontosubcortical pathways mediating cognition, emotion and motor function in CBD are not affected in parallel.

38. AD is a triple proteinopathy • A-beta peptide • Tau • α-synuclein : more in amygdala