Neuropsychiatric disturbances in atypical parkinsonian disorders

Figures & data

Figure 1 Flowchart of the search and selection process.

Table 1 Summary of studies on neuropsychiatric disturbances in MSA

Reference	Sample	Study design	Aim	Methods	Main results	Quality score
Pilo et al, 1996^Citation9	12 MSA, 12 PD	Observational, cross-sectional	Motor disability and mood disorders in MSA and PD	Interview for major depression, BDI	Moderate depressive symptoms in 3 MSA. No major depression detected	I =0 II =1 III =1 IV =1 V =1 VI =1 Total score =4
Gill et al, 1999^Citation10	15 Shy Drager syndrome	Observational, cross-sectional	Frequency and severity of depressive symptoms	BDI (mailed questionnaires)	Depressive symptoms in 13 patients, mild in 9, moderate-severe in 4	I =0 II =0 III =0 IV =0 V =1 VI =1 Total score =2
Fetoni et al, 1999^Citation11	12 MSA, 12 PD	Observational, cross-sectional	Psychiatric disturbances in MSA and PD	BDI, HAMD, BPRS	MSA: 1 dysthymia, 1 major depression	I =0 II =1 III =1 IV =0 V =1 VI =1 Total score =4
Benrud-Larsen et al, 2005^Citation12	99 MSA	Patients identified from computerized database; observational	Depressive symptoms in relation to life satisfaction	BDI (mailed questionnaire)	Mild depressive symptoms in 40 patients, moderate in 30, severe in 7	I =0 II =0 III =2 IV =0 V =1 VI =1 Total score =4
Schrag et al, 2006^Citation13	115 MSA (comparison of data with PD from literature)	Multicenter, observational, cross-sectional	Determinant of quality of life in MSA	BDI, SF36, Compass, and others	Moderate-severe depression in 53 patients. Depression associated with poor HR-QoL. Mean BDI score higher in MSA than in PD (similar disease duration)	I =0 II =0 III =2 IV =0 V =1 VI =1 Total score =4
Kawai et al, 2008^Citation17	21 MSA-C, 14 MSA-P, 21 HC	Observational, case–control	Cognitive dysfunction in MSA-C vs MSA-P	HADS	Higher level of depression both in MSA-C and MSA-P compared to HC, but no differences between the two subtypes	I =0 II =2 III =1 IV =0 V =1 VI =1 Total score =5
Schrag et al, 2010^Citation14	188 PSP, 286 MSA	Multicenter observational, case–control	To compare depression, anxiety, and health status in PSP and MSA	HADS, EQ-5D	55.6% of PSP and 43% of MSA probable depression. 37.3% of PSP and 37.3% of MSA had probable anxiety	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5
Balas et al, 2010^Citation18	25 MSA, 12 PD, 10 HC	Observational, cross-sectional	Cognitive dysfunction and mood in MSA-C vs MSA-P vs HC	Self-evaluation state anxiety, trait anxiety, depression	MSA-P and PD higher level of depression than HC. MSA-C increased level of anxiety compared to HC	I =0 II =2 III =1 IV =0 V =1 VI =0 Total score =4
Winter et al, 2011^Citation15	46 MSA, 40 PSP	Observational, case–control	Factors determining quality of life in PSP and MSA	BDI, EQ-5D	Depression independent predictor of low quality of life	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5
Siri et al, 2013^Citation16	61 MSA, 20 PD	Multicenter, observational, cross-sectional	Cognitive and behavioral features in MSA-P and MSA-C compared to PD	NPI, GDS	Depression in 62% of MSA, 10% of PD. NPI scores similar between MSA and PD; GDS and NPI scores similar in MSA-C and MSA-P	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5
Kawahara et al, 2015^Citation19	33 MSA, 14 cortical cerebellar atrophy, 106 HC	Cross-sectional	Cognitive and affective functions in MSA-C, MSA-P, and cortical cerebellar atrophy	GDS	GDS scores higher in MSA-P, MSA-C, cortical cerebellar atrophy than HC. No differences between the three disorders	I =0 II =2 III =2 IV =0 V =1 VI =1 Total score =6
Cao et al, 2015^Citation20	110 MSA, 55 HC	Cross-sectional	Frontal lobe function and behavioral changes in MSA patients	FBI, FAB, MMSE, others	22.7% of MSA patients had mild frontal lobe dysfunction, 57% moderate, 2.7% severe	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5

Abbreviations: MSA, multiple system atrophy; PD, Parkinson’s disease; PSP, progressive supranuclear palsy; BDI, Beck Depression Inventory; HAMD, Hamilton Rating Scale Depression; BPRS, brief psychiatric rating scale; SF36, Short Form (36) Health Survey; MSA-C, multiple system atrophy cerebellar type; MSA-P, multiple system atrophy parkinsonian type; HC, healthy controls; HADS, Hospital Anxiety and Depression Scale; EQ-5D, EuroQol-5-dimensions; NPI, Neuropsychiatric Inventory; GDS, Geriatric Depression Scale; FBI, Frontal Behavior Inventory; FAB, Frontal Assessment Battery; MMSE, Mini Mental State Examination; HR-QoL, health-related quality of life.

Table 2 Summary of studies on neuropsychiatric disturbances in PSP

Reference	Sample	Study design	Aim	Methods	Main results	Quality score
Menza et al, 1995^Citation34	19 PSP, 42 PD	Observational	Psychiatric symptoms in PSP and PD	DSM-III, Zung Depression Scale; GDS; Zung Self- Rated Anxiety Scale	Major depression in 2, dysthymia in 1, adjustment disorders in 5. No differences between PSP and PD in depression and anxiety measures	I =0 II =1 III =1 IV =0 V =1 VI =2 Total score 6
Maher and Lees, 1986^Citation25	52 PSP	Observational	Clinical features and natural history	Descriptive	At diagnosis: personality changes in 12 patients, depression in 8, emotional lability in 9	I =0 II =0 III =2 IV =0 V =1 VI =0 Total score 3
Esmonde et al, 1996^Citation33	25 PSP, 25 HC	Observational, case–control	Motor, cognitive, and psychiatric disturbances in PSP and HC	BDI	BDI =11–17, n=7, BDI 18–23, n=3, BDI =24 n=3. No correlation between BDI scores, disease severity, and neuropsychological parameters	I =0 II =1 III =1 IV =0 V =1 VI =1 Total score =4
Litvan et al, 1996^Citation27	22 PSP, 20 AD, 40 HC	Observational, case–control	Behavioral symptoms in PSP, AD, and HC	NPI	Apathy in 91%, disinhibition in 36%, dysphoria and anxiety in 18%, irritability, abnormal motor behaviors, or agitation <9%	I =0 II =2 III =2 IV =0 V =1 VI =1 Total score =6
Litvan et al, 1998^Citation28	34 PSP, 15 CBD, 25 HC	Observational, case–control	Behavioral features in PSP, CBD, and HC	NPI	Apathy more frequent in PSP patients. Depression and irritability more frequent in CBD	I =0 II =2 III =2 IV =0 V =1 VI =1 Total score =6
Aarsland et al, 2001^Citation29	61 PSP/144 PD	Observational, case–control	Psychiatric symptoms in PSP and PD. Correlation of neuropsychiatric symptoms with clinical variables	NPI	Total NPI score higher in PSP than in PD. Higher apathy and disinhibition scores in PSP compared to PD	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5
Nath et al, 2003^Citation26	187 PSP	Clinical cohort study	Clinical features and natural history of PSP	No specific rating scales used	At onset personality change in 8 patients, depression, anxiety, and apathy in 5. During the disease, apathy present in 50% of the patients	I =0 II =0 III =2 IV =1 V =1 VI =0 Total score =4
Josephs andDickson, 2003^Citation42	137 PSP, 43 clinically diagnosed as PSP but non- PSP at pathological diagnosis	Clinicopathological correlation	Description of clinical features differentiating PSP from non-PSP	Descriptive case histories	Psychosis in 18% of true PSP and in 44% of non-PSP	I =2 II =1 III =2 IV =1 V =1 VI =0 Total score =7
Papapetropulosand Mash, 2005^Citation43	22 PSP	Clinicopathological correlation	Assessment of visual hallucinations	Descriptive case histories	Visual hallucinations in 2/22 patients	I =2 II =0 III =2 IV =1 V =1 VI =0 Total score =6
Borroni et al, 2008^Citation41	24 PSP, 39 PD, 27 LBD, 16 CBS	Observational, case–control	Frequency, type of behavioral disturbances in the mild stages of PSP, PD, LBD, CBS	NPI	PSP: depression in 50%, anxiety in 40%, sleep disturbances and eating abnormalities in 30%, apathy in 22%	I =0 II =1 III =2 IV =1 V =1 VI =1 Total score =6
Borroni et al, 2009^Citation31	57 PSP/68 CBS	Observational, case–control	Behavioral abnormalities in PSP and CBS	FBI	FBI scores low in both groups. Apathy more frequent in PSP	I =0 II =1 III =2 IV =1 V =1 VI =1 Total score =6
Schrag et al, 2010^Citation14	188 PSP, 286 MSA	Multicenterobservational	To comparedepression, anxiety,and health status inPSP and MSA	HADS, EQ-5D	55.6% of PSP and43% of MSA probabledepression. 37.3% of PSPand 37.3% of MSA hadprobable anxiety	I =0 II =1 III =2 IV =0 V =1 VI =1 Total score =5
Yatabe et al, 2011^Citation37	10 PSP, 13 FTD	Observational,cross-sectional	Compareneuropsychiatricsymptoms,stereotypical, andantisocial behaviorsin PSP and FTD	NPI; StereotypyRating Inventory	NPI comparablebetween PSP and FTD. High scores for apathy,aberrant motor behavior,disinhibition, and lowscores for stereotypicalbehavior in PSP	I =0 II =1 III =0 IV =0 V =1 VI =1 Total score =3
Winter et al, 2011^Citation15	40 PSP, 46 MSA	Observational	Factors determiningquality of life in PSPand MSA	BDI, EQ-5D	Depression independentpredictor of low qualityof life	I =0 II =1 III =1 IV =0 V =1 VI =1 Total score =4
Gersteneckeret al, 2013^Citation30	154 PSP	Multicenter,observational	Type and clinicalcorrelates ofneuropsychiatricprofile in PSP	NPI	Apathy in 62%,depression in 58%,anxiety in 24%, sleepabnormalities in 52%,eating disorders in 39.6%,aggression/agitation in35.6%	I =0 II =0 III =2 IV =0 V =1 VI =1 Total score =4
Bloise et al, 2014^Citation35	28 PSP, 28 HC	Case–controlobservationalstudy	Frequency ofpsychiatric disordersdiffers in patientswith PSP andage-matched healthycontrols	DSM-IV criteriawith structuredinterview HAM-D,HAM-A, BPRS	Psychiatric disturbancesin 15 PSP and in 5 HC.8 PSP patients withdepressive disorders dueto PSP	I =0 II =1 III =1 IV =0 V =1 VI =2 Total score =5

Abbreviations: PSP, progressive supranuclear palsy; PD, Parkinson’s disease; MSA, multiple system atrophy; LBD, Lewy body dementia; HC, healthy controls; AD, Alzheimer’s disease; CBD, corticobasal degeneration; CBS, corticobasal syndrome; FTD, frontotemporal dementia; BDI, Beck Depression Inventory; NPI, Neuropsychiatric Inventory; HADS, Hospital Anxiety and Depression Scale; EQ-5D, EuroQol-5-dimensions; FBI, Frontal Behavior Inventory; GDS, Geriatric Depression Scale; BPRS, brief psychiatric rating scale; DSM-III, Diagnostic and Statistical Manual for Mental disorders, 3rd edition; HAM-D, Hamilton Rating Scale for Depression; HAM-A, Hamilton Rating Scale for Anxiety.

Table 3 Summary of studies on neuropsychiatric disturbances in CBD

Reference	Sample	Study design	Aim	Methods	Main results	Quality score
Mimura et al, 1997^Citation47	3 CBD	Case reports	Clinical characteristics of CBD	Profile of mood status	2 patients with depressed mood	I =0 II =0 III =0 IV =1 V =1 VI =0 Total score =2
Massman et al, 1996^Citation48	21 CBD, 21 AD	Observational, case–control	Neuropsychological functions in CBD and AD	GDS	CBD patients show more depressive symptoms than AD patients	I =0 II =1 III =1 IV =0 V =1 VI =1 Total score =4
Litvan et al, 1998^Citation28	34 PSP, 15 CBD, 25 HC	Observational, case–control	Compare behavioral features of CBD, PSP, and HC	NPI	Apathy more frequent in PSP patients. Depression and irritability more frequent in CBD	I =0 II =2 III =2 IV =0 V =1 VI =1 Total score =6
Wenning et al, 1998^Citation49	14 CBD	Clinicopathological correlation	Natural history of 14 CBD patients with Post-mortem confirmation	Descriptive case histories	Apathy, irritability, disinhibition at disease onset in 3 patients and in 7 at last visit	I =2 II =0 III =0 IV =1 V =1 VI =0 Total score =4
Moretti et al, 2005^Citation52	10 CBD	Observational, with 18 months follow-up	Neuropsychiatric disturbances with respect to asymmetric motor symptoms presentation	BEHAVE-AD delusions, hallucinations, aggressiveness, sleep disturbances, affective disorders, anxiety, and phobias	Patients with left-sided symptoms: more disinhibition, apathy, irritability; patients with predominantly right-sided symptoms: more depression	I =0 II =0 III =0 IV =1 V =1 VI =1 Total score =3
Geda et al, 2007^Citation50	36 CBD	Clinicopathological correlation	Neuropsychiatric features in 36 CBD patients with post-mortem confirmation	Descriptive case histories	Neuropsychiatric disturbances in 8 patients. Type of neuropsychiatric symptoms depending on clinical phenotype	I =2 II =0 III =1 IV =1 V =1 VI =0 Total score =5
Borroni et al, 2008^Citation41	24 PSP, 39 PD, 27 LBD, 16 CBS	Observational	Frequency and type of behavioral disturbances in the mild stages of PSP, PD, LBD, CBS	NPI	Depression in 50%, anxiety in 40%, sleep disturbances and eating abnormalities in 30%, apathy in 22%	I =0 II =1 III =2 IV =1 V =1 VI =1 Total score =6
Borroni et al, 2009^Citation31	57 PSP/68 CBS	Observational	Behavioral abnormalities in PSP and CBS	FBI	FBI scores low in both groups. Apathy more frequent in PSP	I =0 II =1 III =1 IV =0 V =1 VI =2 Total score =5

Abbreviations: CBD, corticobasal degeneration; AD, Alzheimer’s disease; PSP, progressive supranuclear palsy; HC, healthy controls; PD, Parkinson’s disease; LBD, Lewy body dementia; CBS, corticobasal syndrome; GDS, Geriatric Depression Scale; BEHAVE-AD, Behavioral Pathology in AD Rating Scale; NPI, Neuropsychiatric Inventory; FBI, Frontal Behavior Inventory.

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