Behavior and psychological Behavior and psychological symptoms of dementiasymptoms of dementia

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。

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), particu

lar on moderate stage. Severe dementia delusions are rare. (Deutsch, 1991) Cummings (1985), limbic system and temporal lobe change are playe

d 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)

Sleep disturbances (more) : 42 % (Reisberg, 1987) Agitation Irritability Aggression (more) : 20-30 % (Burns, 1990; Deutsch, 199

1) 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 h

ypothalamus. Wander and loss way (more) : 18 %, (Burns, 1990), more f

ound in moderate stage.

NPI studyNPI study

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

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

Behavioral ChangesBehavioral Changes

Percent of subjects

CDR Passive Agitated Selfcentered All three any

0 0 5 5 0 10

1 71 31 43 13 84

2 84 49 71 39 90

3 93 63 66 49 95

All values differ from controls (p < = 0.0001)

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

Depressive Symptoms in SDAT subjectsDepressive Symptoms in SDAT subjects

Feighner symptoms of depressionFeighner symptoms of depression Percent

Reporter CDR Dys Appetite Sleep Energy P-motor Interest Guilt Con Suicidal

Subject 0 28 4 16 19 12 7 7 11 5

1 28 10 11 25 10 27 * 10 47 *** 2

2 16 11 3 5 18 23 3 3 0

Collateral

Source

0 11 4 13 12 4 0 1 1 1

1 26 13 15 35 ** 26 *** 39 *** 12 * 69 *** 15 *

2 21 16 16 29 42 *** 77 *** 11 71 *** 18 **

* P < = 0.01, ** p <= 0.001, *** p <= 0.0001

Dys = dysphoria; P-motor = psychomotor; con = concentration.

CDR 0.5 subjects indicate a pattern similar to those with mild dementia (changes in psychomotor activity, concentration and energy as reported by the collateral source.

Psychotic SymptomsPsychotic Symptoms

Percent

CDR Delusion misidentifications Hallucinations Any

0.5 Rare

0 0 0 0 0

1 21 12 13 29

2 43 24 27 63

3 25 25 25 25

All values differ from controls ( p < = 0.005)

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).

DiscussionDiscussion 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.

Depression vs. dementiaDepression 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。

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.

Core symptoms of depressions Core symptoms of depressions from the DSM-IVfrom 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.

Major characteristics of the dementia syndrome of depressionMajor characteristics of the dementia syndrome of depression

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 progressi

on of intellectual decline Past history of mood disorder Family history of mood disorder Enlarged lateral vertrivles

J L Cummings and DF Benson, Dementia 1992.

Dementia are proteinopathiesDementia are proteinopathies

Principal protein Disease

α-synuclein proteinParkinson’s Disease

Dementia with Lewy Body

Tau proteinF-T dementia and related conditions

Amyloid beta protein Alzheimer’s Disease

SynucleinopathySynucleinopathy

Parkinson diseaseDementia with Lewy bodiesMultiple system atrophyHallervorden-Spatz syndrom

Neuropsychiatric disturbances in PDNeuropsychiatric disturbances in PD

Total sample ( n = 139 ) Patient with symptom present

Mean SD n % of sample Mean SD

Delusion 0.5 1.6 22 15.8 3.3 2.6

Hallucinations 0.9 2.2 37 26.6 3.6 2.9

Agitation 0.7 2.1 23 16.5 4.3 3.5

Depression 1.5 2.6 53 38.1 3.9 2.9

Anxiety 1.0 2.7 28 20.1 5.1 4.0

Euphoria 0.01 0.2 1 0.7

Apathy 1.1 2.9 23 16.5 6.7 3.7

Disinhibition 0.2 0.9 9 6.5 2.7 2.3

Irritability 0.4 1.9 14 10.1 4.4 4.2

Aberrant behavior

0.7 2.3 15 10.8 6.1 3.9

Neuropsychiatric inventory total

7.1 12.0 85 61.2 11.6 13.5

L Neurol Neurosurg Psychiatry 1999; 67:492-6

Neuropsychiatric disturbances in DLBNeuropsychiatric disturbances in DLB

symptoms

Clinical Cohort (N=190) Neuropathological Cohort (N=80)

DLB AD Analysis DLB AD Analysis

N % N % χ² p N % N % χ² p

Hallucination

Visual 71 72 15 16 60.4 *** 26 65 10 25 12.9 ***

Auditory 37 38 5 5 28.8 *** 14 35 4 10 7.2 **

Delusions 56 57 28 30 14.5 *** 24 60 12 30 7.3 **

Delusional misidentification

49 50 18 20 19.3 *** 15 38 2 5 14.1 ***

Major depression 19 19 7 8 5.6 * 13 32.5 5 12.5 4.6 *

Anxiety 40 41 30 33 1.4 n.s. 15 38 10 25 1.5 n.s.

n.s. : no significant; * : p <0.05; ** : p < 0.01; *** : p < 0.001

AM J Psychiatry 1999; 156:1039-1045

REM Sleep Behavior DisorderREM 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 electroph

ysiologic 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 activit

y 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.

REM Sleep Behavior disorder in PD and DLBREM 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.

Neuropsychiatric abnormalities in Neuropsychiatric abnormalities in synucleinopathiessynucleinopathies

Prominent delusions Hallucinations REM sleep behavioral disorder

Other study about DLBOther study about DLB

DLB (n=27) AD (n=17) Significance

Acute confusional states 22 % 12 % n.s.

Visual hallucinations Once only

26 % 6 %

p <0.001Visual hallucinations persistent

67 % 0 %

BEHAVE-AD 10.0 (5.9) 3.1(4.5) p <0.001

Z Walker et al. J neurol Neurosury Psychiatry 2002; 73:134-140

TauopathiesTauopathies

Frontotemporal lobar degeneration Progressive supranuclear palsy Corticobasal degeneration

Frontal- subcortical systemsFrontal- subcortical systems

Executive dysfunction Apathy Disinhibition Repetitive and compulsive behaviors with rituals Hallucinations and sleep disturbances unusual

Frontal systemsFrontal systems

Primary motorPremotorFrontal eye fieldsDorsolateral prefrontalOrbital prefrontalAnterior cingulate circuit

BPSD, Mega and Cummings (1994)

Dorsolateral prefrontalDorsolateral prefrontal

Poor organizational strategiesPoor memory search strategiesStimulus-bound behavior/ environmental

dependencyImpaired set shifting and maintenanceVerbal-manual dissociation

Orbital prefrontalOrbital prefrontal

Personality change: Irritability, Tactlessness, Fatuous euphoria, Impulsivity, Undue familiarity

Environmental dependency: Utilization behavior, imitation behavior

Mood disorders: lability, maniaO.C.D (with increased orbitofrontal and cau

date metabolism)

Anterior cingulate circuitAnterior cingulate circuit

Impaired motivation:

Akinetic mutism

Marked apathy

Psychiatry emptiness

Poverty of spontaneous speech

Indifference to painPoor response inhibition

Other study about corticobasal degenerationOther study about corticobasal degeneration Litvan I, Cummings J.L., Mega M. Neuropsychiatric features of co

rticobasal 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 l

ess. 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 co

gnition, emotion and motor function in CBD are not affected in parallel.

AD is a triple proteinopathyAD is a triple proteinopathy

A-beta peptide Tau α-synuclein : more in amygdala

Neuropsychiatry Dementia Implicated Protein abnormality

Regional Vulnerability

HallucinationPD with dementia

DLBα-synuclein

Brainstemlimbic cortex neocortex

Delusion

PD with dementia

DLB

AD

α-synucleinBrainstemlimbic cortex neocortex

REM sleep behavior disease

PD with dementia

DLBα-synuclein

Brainstemlimbic cortex neocortex

Disinhibition

F-T dementia

PSP

AD (frontal variant)

TauFrontal cortex or frontal-subcortical systems

O.C.BF-T dementia

PSPTau

Frontal cortex or basal ganglia

Apathy

F-T dementia

PSP

AD

TauFrontal cortex and basal ganglia

Ann Neurol 2003; 54 :147-154