Sleep disturbance in mild to moderate Alzheimer's disease

doi:10.1016/j.sleep.2004.12.005

Sleep Medicine

Volume 6, Issue 4, July 2005, Pages 347-352

https://doi.org/10.1016/j.sleep.2004.12.005 Get rights and content

Abstract

Background and purpose

To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates.

Patients and methods

Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis.

Results

The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD ‘aggressiveness’ (P=0.009) and ‘global rating’ (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD.

Conclusions

Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.

Introduction

Sleep disturbance in Alzheimer's disease (AD) is common. Cross-sectional studies of clinic- and community-based studies have reported that up to 40% of patients with AD have sleep disturbance [1].

The cause of sleep disturbance in AD is thought to be multi-factorial. Pathophysiological changes resulting from the disease itself interfere with the maintenance of normal sleep. Damage to neuronal pathways, such as the cholinergic pathways, that initiate and maintain sleep is thought to contribute to sleep changes in AD [2]. The circadian pacemaker, in the suprachiasmatic nucleus, is also important in maintaining a normal sleep-wake cycle. Researchers have demonstrated dysregulation of the circadian timing system in AD, and this may play a role in the development of sleep disturbance [3].

Sleep disturbance is also known to occur as part of associated medical and psychiatric illnesses, such as chronic obstructive airways disease, arthritis, nocturia, and depression, which are frequently diagnosed in patients with AD [4].

For patients with dementia, sleep disturbance will reduce quality of life, and some reports suggest that it is associated with cognitive and functional decline [5], [6]. For caregivers, sleep disturbance is a source of physical and psychological burden and is often cited as a reason for a family's decision to institutionalise a patient [7], [8].

It is therefore important that sleep disturbance in AD is recognised and treated appropriately. Recognition of associated symptoms may help in determining the cause of sleep disturbance in AD. It may also assist the clinician in choosing an appropriate treatment and reduce the likelihood of polypharmacy.

The aim of this study is to determine the prevalence of sleep disturbance in a memory clinic population of patients with AD and identify its clinical correlates.

Section snippets

Method

The sample was recruited through Mercer's Institute for Research on Ageing (MIRA), a national referral centre for people with memory difficulties. All first-appointment attendees who fulfilled the National Institute for Neurological and Communicative Disorders/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) consensus criteria for probable AD were included [9]. This consensus diagnosis was assigned at a Consultant Geriatrician and Consultant Psychogeriatrician led consensus

Results

Fifty-eight percent of the sample lived with their informant, and 94.2% were first-degree relatives of their informant. There was no difference in the sleep-disturbed compared to the non-sleep-disturbed group in terms of relationship to informant.

Of the 224 people evaluated 55 (24.5%) had sleep disturbance. The mean age of the sample was 74.91 years (SD=7.74). There was no significant difference between the sleep-disturbed and the non-sleep-disturbed group with regard to age (95%

Discussion

Before discussing these results it is important to address methodological issues.

While the BEHAVE-AD is a well established and widely used tool for assessing behavioural and psychological symptoms of AD it is not an ideal tool for assessing sleep disturbance. It provides limited information on sleep maintenance, and no detail of sleep times or other sleep parameters. It is important to remember this when considering the findings. Unfortunately to date there is no sleep questionnaire validated

References (38)

M.F. Folstein et al.
Minimental state; a practical method for grading the cognitive state of patients for clinicians
J Psychiatry Res
(1975)
M.V. Vitiello et al.
Sleep complaints cosegrate with illness on older adults. Clinical research informed by and informing studies of sleep
J Psychosom Res
(2002)
P.R. Gehrman et al.
Sleep-disordered breathing and agitation in institutionalised Adults with Alzheimer's disease
Am J Geriatr Psychiatry
(2003)
S. Ancoli-Israel et al.
Effect of light on agitation in institutionalised patients with severe Alzheimer' disease
Am J Geriatr Psychiatry
(2003)
P. Dykierek et al.
The value of REM sleep parameters in differentiating Alzheimer's disease from old-age depression and normal aging
J Psychiatr Res
(1998)
P.N. Prinz et al.
Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type
Neurobiol Aging
(1982)
B.D. Carpenter et al.
Sleep disturbance in community-dwelling patients with Alzheimer's disease
Clin Gerontol
(1995)
M.V. Vitiello et al.
Sleep disturbances in patients with Alzheimer's disease
CNS Drugs
(2001)
K. Mishima et al.
Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons
Chronobiol Int
(2000)
R. Migliorelli et al.
Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease
Am J Psychiatry
(1995)

J.A. Mortimer et al.

Predictor's of cognitive and functional progression in patients with probable Alzheimer's disease

Neurology

(1992)

K.E. Moe et al.

Symposium: cognitive processes and sleep disturbances: sleep/wake patterns in Alzheimer's disease: relationships with cognition and function

J Sleep Res

(1995)

C. Donaldson et al.

Determinants of carer stress in Alzheimer's disease

Int J Geriatr Psychiatry

(1998)

T. Hope et al.

Predictors of institutionalization for people with dementia living at home with a carer

Int J Geriatr Psychiatry

(1998)

G. McKhann et al.

Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease

Neurology

(1984)

B. Reisberg et al.

Behavioural symptoms in Alzheimer's disease: phenomenology and treatment

J Clin Psychiatry

(1987)

J.L. Mack et al.

The evaluation of behavioural disturbance in Alzheimer's disease: the utility of three rating scales

J Geriatr Psychiatry Neurol

(1994)

S.G. Sclan et al.

The behaviour pathology in Alzheimer's disease rating scale (BEHAVE-AD): reliability and analysis of symptom category scores

Int J Geriatr Psychiatry

(1996)

G. Blessed et al.

The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects

Br J Psychiatry

(1968)

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Original articleSleep disturbance in mild to moderate Alzheimer's disease

Abstract

Background and purpose

Patients and methods

Results

Conclusions

Introduction

Section snippets

Method

Results

Discussion

J Psychiatry Res

J Psychosom Res

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

J Psychiatr Res

Neurobiol Aging

Sleep disturbance in community-dwelling patients with Alzheimer's disease

Clin Gerontol

Sleep disturbances in patients with Alzheimer's disease

CNS Drugs

Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons

Chronobiol Int

Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease

Am J Psychiatry

Predictor's of cognitive and functional progression in patients with probable Alzheimer's disease

Neurology

Symposium: cognitive processes and sleep disturbances: sleep/wake patterns in Alzheimer's disease: relationships with cognition and function

J Sleep Res

Determinants of carer stress in Alzheimer's disease

Int J Geriatr Psychiatry

Predictors of institutionalization for people with dementia living at home with a carer

Int J Geriatr Psychiatry

Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease

Neurology

Behavioural symptoms in Alzheimer's disease: phenomenology and treatment

J Clin Psychiatry

The evaluation of behavioural disturbance in Alzheimer's disease: the utility of three rating scales

J Geriatr Psychiatry Neurol

The behaviour pathology in Alzheimer's disease rating scale (BEHAVE-AD): reliability and analysis of symptom category scores

Int J Geriatr Psychiatry

The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects

Br J Psychiatry

Original article
Sleep disturbance in mild to moderate Alzheimer's disease