A comparison of sleep profiles in patients with dementia with lewy bodies and alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRYInt[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999# J[ B[ GRACE0 \ M[ P[ WALKER1 AND I[ G[ MCKEITH2 0 Lecturer in Psychiatry\ Department of Old A`e Psychiatry\ Wolfson Research Unit\ Newcastle General Hospital\ 1 MRC Research Assistant\ MRC Neuropatholo`y Unit\ Newcastle General Hospital\ Newcastle upon Tyne\ UK 2 Professor of Old A`e Psychiatry\ Wolfson Research Unit\ Newcastle General Hospital\ Newcastle upon Tyne\ UK Introduction[ Sleep disturbances are common in healthy old age and in dementia syndromes[ Polysomnography has demonstrated typical changes in both Alzheimer|s disease "AD# and dementia with Lewy bodies "DLB# with ADbeing characterised by sundowning and sleep apnoea and DLB patients showing more disturbances of movementcontrol during sleep[ The technical di.culties associated with EEG sleep recordings mean that polysomnography isnot possible out of specialist centres[ Objectives[ To use questionnaires to assess the frequency of sleep disturbances in patients with Alzheimer|s disease Method[ The sleep pro_les of twenty patients with AD and 06 with DLB were assessed using three questionnaires\ one designed to assess night time sleep disturbance\ one day time sleepiness and the last carer burden[ The sleepquestionnaires were repeated in a subgroup after treatment with a cholinesterase inhibitor "rivastigmine#[ Results[ Level of sleep disturbance in both groups was high[ DLB patients had more overall sleep disturbance\ more movement disorders whilst asleep and more abnormal day time sleepiness[ Treatment with rivastigmineproduced a trend towards normalisation of sleep pro_le in a small number of subjects[ Conclusions[ Both groups have extensive sleep problems[ The DLB and AD groups have di}erent sleep pro_les that are of diagnostic importance and may suggest di}erent treatment strategies[ The results are consistent with thosefound from polysomnographic assessment and suggest that the questionnaires used are sensitive to detect di}erencespreviously documented with polysomnography[ KEY WORDS*Alzheimer|s disease^ dementia with Lewy bodies^ sleep^ cholinesterase inhibitors taking or in the standard textbooks[ In a Medlinesearch for the years 0882 to date\ only 565 out of Alzheimer|s disease "AD# and dementia with Lewy 63 987 papers\ less than 0)\ published with a key bodies "DLB# are both common progressive word of {old| or {elderly|\ mention sleep in the title dementing illnesses associated with changes in sleep pro_le[ Sleep disturbance adds to carer bur! In patients with AD the most common sleep den and may lead to the prescription of additional behaviours are a tendency to confusion in early evening "sundowning# and wandering at night Despite the frequency and severity of sleep dis! "Ancoli!Israel et al[\ 0882\ 0883#[ Daytime napping turbance in the elderly\ little attention is paid to is increased compared to age!matched controls[ sleep disturbance in schemes for psychiatric history The degree of sleep disturbance\ both assessed byclinical observation and polysomnography\ tendsto worsen as memory impairment worsens "Pol! Correspondence to] Dr J[ B[ Grace\ SpR in Old Age lack\ 0886#[ An accurate description of the changes Psychiatry\ Castleside Unit\ Newcastle General Hospital\Newcastle found in sleep in AD is hampered by the fact that many studies do not di}erentiate between mild\ Copyright Þ 1999 John Wiley + Sons\ Ltd[ SLEEP PROFILES IN PATIENTS WITH DLB AND AD moderate and severe dementia and the diagnosis is previously documented sleep disorders in groups often less than rigorous[ Sleep apnoea may also of patients with AD and DLB[ Measurements were be more common in dementia patients than age! made of night!time behaviour disturbance\ day! matched controls "Bahro et al[\ 0882^ Bader et al[\ A small subset of the DLB patients were enrolled Typical electro!encephalographic changes have in an open label study of rivastigmine\ a chol! been described in AD as showing a relative inesterase inhibitor\ enabling a pilot study of the decrease in the proportion of rapid eye movement e}ects of this class of drugs on sleep:wake cycles[ "REM# sleep "Ancoli!Israel et al[\ 0883#[ As REMsleep is generated and maintained by cholinergicactivity\ this is a predictable consequence of the marked loss of cholinergic neurones[ Corticallyexpressed EEG events such as sleep spindles and Patients were recruited from a specialist centre in K complexes are less frequent in patients with AD old age psychiatry\ either from day hospital con! than in age!matched controls and occur less often tact or memory clinic assessments[ Patients were recruited consecutively after initial assessment by DLB is associated with abnormal control of con! the clinical team[ All patients with a possible diag! sciousness throughout the day\ with ~uctuations nosis of AD or DLB were screened for possible in arousal and alertness[ Patients with DLB have inclusion in the study[ If they met the recently subcortical and cortical cholinergic de_cits greater agreed consensus criteria for DLB "McKeith et al[\ than those seen in AD and alteration in cholinergic 0885# or National Institute of Neurological and activity may underlie the ~uctuating level of con! Communicative Disorders and Stroke "NINCDS# sciousness observed in 79) of these patients "McKhann 0873# criteria for probable AD and "Byrne\ 0878^ Perry et al[\ 0887#[ Sleep in DLB has had a carer able to give a sleep history\ they were not been as extensively investigated as in AD\ but approached to take part in the study[ Patients with abnormal control of motor function during sleep a recorded diagnosis of depression or chronic pain appears to be common[ This may present as REM were excluded from this study as they may be pre! sleep behaviour disorder "RSBD#\ which is charac! terised by a loss of the muscle atonia normally For each subject\ the Mini State Examination seen in REM sleep and an {acting out| of dreams "MMSE^ Folstein et al[\ 0864# was used to provide "Schenk\ 0886^ Boeve et al[\ 0887#[ Normal REM a simple global measure of cognitive functioning sleep is characterised by muscle atonia particularly and CDR "clinical dementia rating scale# was used a}ecting the antigravity muscles and is initiated to stage the degree of global severity[ Details of by cholinergic brainstem neurones[ RSBD is more common in Parkinson|s disease "inter alia Cornella The sleep scales used were the Epworth Sleepi! et al[\ 0882\ 0887#\ multiple system atrophy "Plazzi ness Scale "ESS^ Johns\ 0882#\ which is an eight! et al[\ 0886^ Tachibana\ 0886# and DLB "Boeve item scale designed to quantify daytime sleepiness et al[\ 0887# than in age!matched controls[ It is and tendency to {nap| by rating the likelihood of hypothesised that some sleep disturbance at night\ falling asleep in di}erent situations on a scale of especially the periodic limb movements\ bad dre! {never| to {highly likely|\ scoring 9Ð2 for each time\ ams and confusion on waking\ are a result of REM giving a range of 9Ð13[ The Pittsburgh Sleep Qual! sleep abnormalities[ Detailed electro!physiological ity Inventory "PSQI^ Buysee et al[\ 0877# is a seven! sleep work has yet to be done in DLB\ but the component scale designed to measure sleep dis! more profound cholinergic de_cits seen could be turbance over the preceding month[ Each com! predicted to cause extensive disruption to sleep ponent has a value on the scale of 9 "no sleep architecture\ particularly REM related phenom! disturbance# to 2 "high level of sleep disturbance#\ giving a ratio of 9Ð10[ It has been validated in Although changes in 13!hour arousal are com! nursing home populations "Gentili et al[\ 0884#[ mon in both AD and DLB and are clinically The carer distress scale from the sleep item of the important\ physiological measures of sleep pro_le Neuropsychiatric Inventory "NPI^ Cummings et such as EEG polysomnography are time consum! al[\ 0883# was used\ rating distress over the pre! ing\ expensive and limited to a few centres[ In this ceding 3 weeks on a six!point scale from 9 to 5 paper sleep questionnaires are used to quantify the "{not a problem| to {very severe problem|#[ Copyright Þ 1999 John Wiley + Sons\ Ltd[ Int[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999# For the patients on rivastigmine\ all the rating more distress at sleep disturbances in the DLB scales were repeated after 01 weeks of treatment group than the AD group\ with 05:06 saying that sleep problems were a stressor compared with 7:19in the AD group "Table 1#[ A stressor was de_nedas a carer rating of moderate\ severe or very severe In quantifying speci_c night!time sleep prob! Seventeen patients with DLB and 19 with AD were lems\ DLB patients were more likely to dem! recruited from either day hospital care or com! onstrate periodic limb movements\ confusion on munity psychiatric nurse "CPN# contact[ All were waking DLB\ and bad dreams than the AD group[ under the care of a psychogeriatrician[ Six patients The scales used detected no signi_cant di}erence with DLB were started on rivastigmine and mea! between groups in subjective sleep quality\ latency sures were repeated after 01 weeks| treatment at In the small subgroup treated with rivastigmine The AD and DLB groups were similar in terms at maximum tolerated dose there was a reduction of age\ gender\ and cognitive impairment\ as mea! in both ESS and PSQI scores and reduced inci! sured by the MMSE\ and level of global severity\ dence of individual troublesome night!time behav! as measured by CDR "Table 0#[ Six out of 19 "29)# of the AD patients and 4 out of 06 "18)# movements and confusion on waking "Table 3#[ of the DLB patients were on hypnotic medication[ None of these patients were on hypnotic medi! More men than would be expected were recruited[ cation[ Due to the small numbers\ statistical analy! This may be due to the exclusion of many female patients as they had no carer to provide a history[ Both groups demonstrated a tendency to fall asleep during the day\ as measured by the ESS[ The data show that the DLB group had a greatertendency to fall asleep at inappropriate times dur! The three questionnaires used in this paper dem! ing the day[ The DLB group also demonstrated onstrated a high incidence of sleep disturbance in more night!time sleep disturbance[ Carers reported both AD and DLB patients[ Disturbances in the Table 0[ A comparison of baseline characteristics of the two groups Table 1[ Sleep characteristics of AD and DLB patients Copyright Þ 1999 John Wiley + Sons\ Ltd[ Int[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999# SLEEP PROFILES IN PATIENTS WITH DLB AND AD Table 2[ Description of sleep characteristics Subjective sleep quality bad or fairly bad Sleep latency on average more than 29 min Sleep duration less than 5 hours per night Table 3[ Change in sleep characteristics after treatment control of wakefulness and sleep are apparent in groups shows a much greater tendency for the both groups[ DLB patients had higher levels of DLB group to sleep during the day[ Fluctuations sleep disturbance overall and speci_cally had more in consciousness are an integral part of the diag! abnormalities in areas such as control of move! nosis of DLB and from the tools used it is di.cult ment "periodic limb movements#\ bad dreams and to separate ~uctuation in arousal from sleep[ The confusion on waking[ These _ndings imply that ESS\ however\ measures the tendency to fall asleep the ESS and PSQI detect some of the di}erences in a variety of situations\ perhaps indicating a in sleep pro_le previously documented using poly! lower level of innate arousal in this patient group or re~ecting the sleep de_cit arising from a dis! The questionnaires used take approximately 04 minutes to administer and give a quanti_ed The simple carer distress measure used indicates measurement of sleep disturbances[ Although the that the problems of sleep disturbance in both PSQI has been previously validated in nursing types of dementia are a signi_cant cause of distress home populations\ neither it nor the ESS are exten! to carers[ The low incidence of prescribed night! sively used in psychiatric practice[ Although the time medication may represent a reluctance on the gold standard for the detection of sleep disturbance part of psychogeriatricians to prescribe addictive remains polysomnography "PSG# and daytime benzodiazepines or potentially dangerous neuro! sleepiness can only be de_nitively assessed by inter! leptics\ a lack of enquiry on the part of the treating vention measures such as the multiple sleep latency doctor or previous ine}ectual treatment with hyp! test\ whereby tendency to nap is monitored by an notic medication[ As discussed earlier\ the typical observer and EEG recording\ the tools used in this change in sleep pro_le in AD and DLB is charac! study are brief and easily administered\ showing a terised by a loss of REM sleep and as most benzo! clear di}erence between the diagnostic groups and diazepines and sedating antidepressants are REM a possible improvement in sleep between treated suppressors\ they may have a paradoxical e}ect on sleep[ However\ if sleep disturbances are related to A comparison of the ESS score between the Copyright Þ 1999 John Wiley + Sons\ Ltd[ Int[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999# Ancoli!Israel S\ Kripke DF\ Klauber MR\ Parker L\ Stepnowsky C\ Kullen A\ Fell R[ 0882[ Natural his!tory of sleep disordered breathing in community , Patients with AD and DLB have high levels dwelling elderly[ Sleep 05] S14ÐS18[ of sleep disturbance both during the day and Bader GG\ Turesson K\ Wallin A[ 0885[ Sleep related breathing and movement disorders in healthy elderly , DLB patients have more sleep disturbance and demented subjects[ Dementia 6] 168Ð176[ Bahro M\ Riemann D\ Stadtmuller G\ Berger M\ Gattaz WF[ 0882[ REM sleep parameters in the dis! , Sleep questionnaires are su.ciently sensitive crimination of probable Alzheimer|s disease from old!age depression[ Biol Psychiat 23"6#] 371Ð375[ to discriminate between sleep patterns in AD Boeve BF\ Silber MH\ Ferman TJ\ Kokmen E\ Smith GE\ Ivnik RJ\ Parisi JE\ Olson EJ\ Petersen RC[ 0887[ REM sleep behavior disorder and degenerative , A small pilot study suggests that rivastigmine may correct some of the sleep disturbances Buysee DJ\ Reynolds CF\ Monk TH\ Berman SR\ Kupfer DJ[ 0877[ The Pittsburgh Sleep Quality Index]a new instrument for psychiatric practice andresearch[ Psychiat Res 17] 082Ð102[ Byrne EJ\ Lennox G\ Lowe J\ Godwin!Austen\ RB[ pressing medication may have a bene_cial e}ect 0878[ Di}use Lewy body disease] clinical features in 04 cases[ J Neurol Neurosur` Psychiatry 41] 698Ð600[ The early indications from the small number of Cornella CL\ 0882[ REM abnormalities in Parkinson|s patients started on rivastigmine are that there is a disease[ 0882[ Ann Neurol 23] 609[ reduction in the level of sleep disturbance\ with a Cornella CL\ Nardine TM\ Diedrich NJ\ Stebbins GT[ fall in PSQI and a reduction in carer burden[ "Six 0887[ Sleep related violence\ injury and REM sleepbehaviour disorder in Parkinson|s disease[ Neurolo`y out of six reported an improvement in night!time behaviour[# Rivastigmine also reduced daytime Cummings JL\ Mega M\ Gray K\ Rosenberg!Thompson sleepiness\ as re~ected in the fall in ESS\ perhaps demonstrating the role of the cholinergic system in ropsychiatric Inventory] comprehensive assessment of the control of arousal[ If larger trials show an psychopathology in dementia[ Neurolo`y 33] 1297Ð improvement in sleep pro_le with the prescription of cholinesterase inhibitors for the treatment of Folstein MF\ Folstein SE\ McHugh PR[ 0864[ {{Mini! cognitive impairment or non!cognitive symptoms mental state||] A practical method for grading the of dementia\ the need for more potentially danger! cognitive state of patients for the clinician J Psychiatr ous drugs such as benzodiazepines or neuroleptics Gentili A\ Weiner DK\ Kuchibhatla M\ Edinger JD[ 0884[ TestÐretest reliability of the Pittsburgh SleepQuality Index in nursing home residents[ J Am Geriatr Johns MW[ 0882[ Sleepiness\ snoring and obstructive Distressing night!time behaviours and daytime sleep apnoea] the Epworth Sleepiness Scale[ Chest sleepiness are common in AD and DLB\ but are more common in DLB[ Few patients are on hyp! McKhann G\ Drachman D\ Folstein M\ Katzman R\ notic medication[ The scales used in this study are Price D\ Stadlan EM[ 0873[ Clinical diagnosis of Alz! sensitive enough to detect the di}erences between heimer|s disease] Report of the NINCDS!ADRDAWork Group under the auspices of Department of AD and DLB patients\ con_rming the di}erences Health and Human Services Task Force on Alz! seen in polysomnography studies[ Disruptions in heimer|s Disease[ Neurolo`y 23"6#] 828Ð833[ night!time behaviour and excessive daytime sleepi! McGa.gan S\ Bliwise DL[ 0886[ The treatment of sun! downing[ A selective review of pharmacological andnon pharmacological studies[ Dru`s A`in` 09"0#] 09Ð McKeith IG\ Galasko D\ Kosaka K et al[ 0885[ Con! Ancoli!Israel S\ Klauber MR\ Gillin JC\ Campbell SS\ sensus guidelines for the clinical and pathologic diag! Hofstetter CR[ 0883[ Sleep in non!institutionalised nosis of dementia with Lewy bodies[ Neurolo`y 36"4#] Alzheimer|s patients[ A`in` 5"5#] 340Ð347[ Copyright Þ 1999 John Wiley + Sons\ Ltd[ Int[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999# SLEEP PROFILES IN PATIENTS WITH DLB AND AD Perry EK\ Walker M\ Grace J\ Perry RH[ 0887[ Ace! dents and their caregivers[ J Amer Geriatr Soc 34] tylcholine in mind[ Trends Neurosci 11"5#] 162Ð179[ Plazzi G\ Corsini R\ Provini F\ Pierangeli G\ Martinelli Tachibana N\ Kimura K\ Kitajima K\ Shinde A\ P\ Montagna P\ Lugaresi E\ Cortelli P[ 0886[ REM Kimura J\ Shibasaki H[ 0886[ REM sleep motor dys! sleep behavior disorders in multiple system atrophy[ function in multiple system atrophy] With special emphasis on sleep talk as its early clinical mani! Pollak CP\ Stokes PE[ 0886[ Circadian Rest!Activity in festation[ J Neurol Neurosur` Psychiatry 52"4#] 567Ð demented and nondemented older community resi! Copyright Þ 1999 John Wiley + Sons\ Ltd[ Int[ J[ Geriatr[ Psychiatry 04\ 0917Ð0922 "1999#

Source: http://walkerlab.berkeley.edu/reprints/Grace_Walker_IntGerPsych_2001.pdf