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Rapid Eye Movement Sleep Deprivation in Elderly Patients With Concurrent Symptoms of Depression and Dementia DanielJ. Buysse, M.D. Charles F. Reynolds III, M.D. Carolyn C. Hoch, Ph.D., R.N. Patricia R. Houck, M.S.H. Susan R. Berman, B.S. Janette Matzzie, R.PSG.T. DavidJ. Kupfer, M.D.

Rapid

eye movement

(REM)

sleep

measures

distin-

guish elderly patients with depression from those with dementia. The authors used a 2-night REM sleep deprivation (RSD) protocol to characterize patients with mixed symptoms of depression and dementia in comparison with patients with “pure” depression or dementia and healthy controls. Mixed-symptom patients resembled dementia patients in baseline sleep measures, but their large change in phasic REM activity following RSD suggests neurobiological similarities to depression. Mixed-symptom patients with stable cognitive impairment had greater REM sleep rebound than those with a more progressive dementing course. These results are consistent with previous neuropathological and neurochemical data. (The Journal Neurosciences

of Neuropsychiatry 1992;

4:249-256)

and

Clinical

E

lderly patients with mixed symptoms of depression and dementia do not constitute a homogeneous population. Following treatment for depression some show stability, or even improvement, in cognitive function,1 but others show progressive cognitive impairment similar to that seen in primary degenerative dementia, despite response of depressive symptoms to treatment.2’3 Baseline clinical ratings differ in the expected directions for mixed-symptom patients with nonprogressive versus progressive cognitive impairment: depressive symptoms are more severe in the former group, and symptoms of cognitive impairment are more severe in the latter.4 In one study, individual items from rating scales accurately discriminated 90.5% of patients with progressive versus nonprogressive courses.4 Treatment response to antidepressants also differentiates mixed-symptom patients with nonprogressive versus progressive cognitive impairment.5’6 Electroencephalographic (EEG) sleep patterns, both during baseline sleep and during recovery sleep following total sleep deprivation (TSD), provide another means of examining neurobiological differences in patients with depression, dementia, and mixed symptoms.79 Specifically, patients with depression have more early-morning wakefulness (REM)

Received

April19,

10,

From

1991.

NEUROPSYCHIATRY

higher

amounts

phasic

REM

1991; the

of

3811

Street,

O’Hara

Copyright

OF

and

and

Department

Dr. Buysse

JOURNAL

sleep

Sleep

revised

Western PA

eye

than

Rhythms Psychiatric

15213.

Address

movement

patients

8, 1991;accepted

Biological

Pittsburgh,

at the above © 1992

November

and

Psychiatry,

of rapid

activity

Research Institute reprint

with

November Program,

and

Clinic,

requests

to

address.

American

Psychiatric

Press,

Inc.

249

REM

SLEEP,

DEPRESSION,

AND

DEMENTIA

dementia. Following TSD, depressed patients have a greater reduction of depressive symptoms and more robust REM sleep rebound than demented patients. Results in the same direction are seen for mixed-symptom patients with nonprogressive cognitive impairment versus those with progressive cognitive impairment: the former group has more REM sleep at baseline, a greater antidepressant response to TSD, and a more robust REM rebound following TSD.9 Recent results using REM sleep deprivation (RSD) by awakenings again indicate differences between patients with depression and patients with dementia in REM sleep measures at baseline and during recovery sleep.’#{176}These findings suggest that EEC sleep measures, and in particular REM sleep measures, can assist in diagnostic discrimination and help to reveal the underlying neurobiological heterogeneity. Specifically, the REM sleep findings are consistent with theories suggesting cholinergic supersensitivity in depression11 and cholinergic underactivity in dementia,’2 and they suggest that these relative neurochemical changes may extend to subgroups of mixed-symptom patients. The current study examines the responses to RSD by awakenings in patients with concurrent symptoms of depression and dementia. Based on previous findings, we hypothesized that:

evaluation, and treatment following sleep studies have also been discussed previously’0 and will be summarized briefly here. Patients and control subjects examined in the current RSD study did not participate in TSD studies previously reported by our group.8’9 Demographic and clinical data for the current group of subjects are presented in Table 1. Patients with serious, unstable, or rapidly progressive medical illnesses, as well as those with psychiatric diagnoses other than depression or dementia, were excluded. All patients had a thorough medical history and physical examination as well as screening laboratory blood studies, CT or MRI studies of the head, and waking EEGs. All patients were free of psychotropic drugs for at least 14 days prior to sleep studies. Psychiatric diagnoses were made according to Research Diagnostic Criteria, using the Schedule for Affective Disorders and Schizophrenia (SADS/RDC)13 as well as DSM-III)4 Mixed-symptom patients had diagnoses of major depression (9 with probable and 5 with definite endogenous subtype) or primary degenerative dementia with depression. However, in contrast to patients with “pure” depression or dementia seen at our institution, all of the current mixed-symptom patients had substantial evidence of both depression and cognitive impairment, regardless

1.Mixed-symptom tween patients terms of REM

patients would be intermediate bewith “pure” depression or dementia in sleep and sleep continuity measures,

both at baseline and following the challenge of RSD. 2. Mixed-symptom patients with a more “depressive” clinical course (i.e., nonprogressive cognitive impairment) would have higher measures of phasic and tonic REM activity at baseline and after RSD than those with a more “dementing” course (i.e., progressive cognitive impairment).

METHODS Patients study included 18 inpatients and I outpatient with concurrent symptoms of depression and dementia, recruited from the psychogeriatric units at the Western Psychiatric Institute and Clinic and the Benedum Geriatric Center, both at the University of Pittsburgh. For comparison, we examined a group of healthy control subjects (n = 15), a group of patients with depression and no evidence of dementia (n = 14), and a group of patients with dementia and no evidence of depression (n = 15). Responses to REM sleep deprivation (RSD) in these latter three groups have been discussed in a previous report.’#{176} Methods of patient recruitment, medical and psychiatric This

250

of

their

initial

primary

diagnosis.

Clinical

ratings included the Hamilton Rating Scale for Depression (HRSD),’5 the Folstein Mini-Mental State Exam (MMSE),’6 the Blessed Dementia Index,’7 the Clinical Dementia Rating Scale,18 and the Hachinski Modified Ischemia Scale. 19 All mixed-symptom patients were required to have an HRSD score of 10 and an MMSE score of 25. Although these represent lenient severity criteria, mean scores for the mixed-symptom patients indicate at least moderate severity of both depressive and dementia symptoms (see Table 1). Following the RSD protocol, mixed-symptom patients were treated openly with nortriptyline or electroconvulsive therapy, as previously described.6 Follow-up clinical ratings were obtained every 6 months for up to 2 years by research nurses trained to reliability and blind to baseline diagnoses and sleep results. In an exploratory analysis of the data, two of the authors (D.J.B. and C.F.R.) further categorized each mixed-symptom patient as having either nonprogressive or progressive cognitive impairment. Categorizations were based on the course of clinical ratings alone and were made blind to initial diagnoses and sleep data. No specific criterion values were used to assign patients to nonprogressive versus progressive categories; rather, the pattern and trend of clinical rating scores were considered. For instance, if a patient had low HRSD scores with worsening dementia ratings, the case would be classified “progressive.” If a patient

VOLUME

4

#{149} NUMBER

3

#{149} SUMMER

1992

et al.

BUYSSE

had decreasing HRSD scores change in dementia ratings, “nonprogressive.” as exploratory

Again, rather than

protocol

in detail

according

or little

would

blind

be classified

these classifications definitive.

used

in this

elsewhere.1#{176} Patients

polysomnographic nights,

improvement case

were

seen

sleep

2 RSD

nights,

performed

inpatient

study had

studies,

and

and

in the

been

nights

sleep

Sleep

entire

RSD

protocol.

mixed-symptom

1 patient

could

group

not

nonprogressive,

recovery nights and analyses of delta

activity

were

as previously

include

data

placed

asymmetrically

EOG

speed

was

TABLE

1.

for

the

for

the

Because

two

or

mixed-symptom

at the

and one channel High and low were

30 Hz and

10 mm/sec.

one

channel

of study

outer

canthi

to with

and

were

and visually

units

“REM asleep

REM

for

intensity” in minutes.

performed

Age Gender,male/female Race, white/black

paper

with the

a zero-cross number

of rapid

eye

of

half-wave 0.5-2 Hz

States

(POMS)

each

ning. Most demented tients required the complete the POMS. Data Analysis All data are ings

presented

as means

Demographic were

variables

analyzed

using

one-way

A Control (a = 15)

B Depressed (a = 14)

C Demented (a = 15)

72.8 ± 5.1

71.7 ± 5.2

75.9

5/10

1/13

± 5.9

D Mixed-Symptom (a = 19) 72.3

4/11

± 9.2 2/17

0.83

0.48

Recurrent/nonrecurrent

-

10/4

months

-

Depressionepisodenumber

Clinical Hachinski

-

onset

OF

unless

analysis

of variance

23.8

± 38.9

43.3

3.3±2.1 57.1

7/12

-

± 27.6

72.4

± 20.2

0.11 1.64

1.9±2.1

3.39

-

63.2±15.3

1.13

± 6.5

69.4 ± 9.1

-

± 17.4

34.1

1.16

3.0 ± 1.6

11.3 ± 6.0

8.3 ± 3.2

146.30”

AC,AD,BC,BD,CD

State score

29.8 ± 0.4

29.5 ± 0.6

16.9 ± 8.5

19.4 ± 5.1

95.54”

AC,AD,BC,BD,CD

± 3.6

5.6 ± 4.5

± 3.8

36.43”

AB,AC,AD,BC,CD

0.0 ± 0.1

0.3 ± 0.2

1.6 ± 0.7

1.3 ± 0.7

180.54”

AC,AD,BC,BD,CD

1.1 ± 0.3

2.0 ± 0.8

1.4 ± 1.2

1.9 ± 1.3

score

Scale score Scale score

as plus or minus

NEUROPSYCHIATRY

rat-

Tukey’s post hoc

0.0 ± 0.0

Ischemia

pato

otherwise clinical

score

Rating

eve-

baseline

-

Scale for Depression

Modified

each

-

Index

Note: Values shown ‘P < 0.05; “P