Disturbed sleep is a major clinical problem in Alzheimer’s disease (AD). Apolipoprotein •4 (APOE •4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE •4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-•4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the •4 allele.
1. Allen SR, Seiler WO, Stahelin HB, Spiegel R. Seventy-two hour polygraphic and behavioral recordings of wakefulness and sleep in a hospital geriatric unit: comparison between demented and nondemented patients. Sleep1987; 10:143-159.
2.
2. Hoch CC, Reynolds CF III, Houck PR. Sleep patterns in Alzheimer, depressed, and healthy elderly. Western J Nursing Res1988; 10:239-256.
3.
3. Martin PR, Loewenstein RJ, Kaye WH, et al. Sleep EEG in Korsakoff’s psychosis and Alzheimer’s disease. Neurology1986; 36:411-414.
4.
4. Reynolds CF III, Hoch CC, Stack J, Campbell D. The nature and management of sleep/wake disturbance in Alzheimer’s dementia. Psychopharmacol Bull1988; 24:43-48.
5.
5. Reynolds CF III, Kupfer DJ, Houck PR, et al. Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data. Arch Gen Psychiatry1988; 45:258-264.
6.
6. Vitiello MV, Prinz PN, Williams DE, et al. Sleep disturbances in patients with mild-stage Alzheimer’s disease. J Gerontol1990; 45:M131-M138.
7.
7. Vitiello MV, Poceta JS, Prinz PN. Sleep in Alzheimer’s disease and other dementing disorders. Can J Psychol1991; 45:221-239.
8.
8. Moe KE, Vitiello MV, Larsen LH, Prinz PN. Sleep/wake patterns in Alzheimer’s disease: relationships with cognition and function. J Sleep Res1995; 4:15-20.
9.
9. Vitiello MV, Borson S. Sleep disturbances in patients with Alzheimer’s disease: epidemiology, pathophysiology and treatment. CNS Drugs2001; 15:777-796.
10.
10. Ancoli-Israel S, Gehrman P, Martin JL, et al. Increased light exposure consolidates sleep and strengthens circadian rhythms in severe Alzheimer’s disease patients. Behav Sleep Med2003; 1:22-36.
11.
11. Donaldson C, Tarrier N, Burns A. Determinants of carer stress in Alzheimer’s disease. Int J Geriatr Psychiatry1998; 13:248-256.
12.
12. McCurry SM, Logsdon RG, Vitiello MV, Teri L. Successful behavioral treatment for reported sleep problems in elderly caregivers of dementia patients: a controlled study. J Gerontol B Psychol Sci Soc Sci1998; 53:122-129.
13.
13. Pollak CP, Perlick D. Sleep problems and institutionalization of the elderly. J Geriatr Psychiatry Neurol1991; 4:204-210.
14.
14. Sanford JRA. Tolerance of debility in elderly dependents by supporters at home: its significance for hospital practice. BMJ1975; 3:471-473.
15.
15. Strittmatter WJ, Roses AD. Apolipoprotein E and Alzheimer’s disease. Annu Rev Neurosci1996; 19:53-77.
16.
16. Asada T, Motonaga T, Yamagata Z, et al. Associations between retrospectively recalled napping behavior and later development of Alzheimer’s disease: association with APOE genotypes. Sleep2000; 23:629-634.
17.
17. Cacabelos R, Rodriguez B, Carrera C, et al. APOE-related frequency of cognitive and noncognitive symptoms in dementia. Meth Find Exp Clin Pharmacol1996; 18:693-706.
18.
18. Friedman L, Kraemer HC, Zarcone V, et al. Disruptive behavior and actigraphic measures in home-dwelling patients with Alzheimer’s disease: preliminary report. J Geriatr Psychiatry Neurol1997; 10:58-62.
19.
19. Yesavage JA, Friedman L, Kraemer HC, et al. A follow-up study of actigraphic measures in home-residing Alzheimer disease patients. J Geriatr Psychiatry Neurol1998; 11:7-10.
20.
20. Yesavage JA, Taylor JL, Kraemer H, et al. Sleep/wake cycle disturbance in Alzheimer’s disease: how much is due to an inherent trait?International Psychogeriatr2002; 14:73-81.
21.
21. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: a report of the NINCDS-ADRDA Work-Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology1984; 34:939-944.
22.
22. Folstein MF, Folstein SE, McHugh PH. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res1975; 12:189-198.
23.
23. Kraemer HC, Taylor JL, Tinklenberg JR, Yesavage JA. The stages of Alzheimer’s disease: a reappraisal. Dement Geriatr Cogn Disord1998; 9:299-308.
24.
24. Murphy GM Jr, Taylor J, Kraemer HC, et al. No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer’s disease. Am J Psychiatry1997; 154:603-608.
25.
25. Pat-Horenczyk R, Klauber MR, Shochat T, Ancoli-Israel S. Hourly profiles of sleep and wakefulness in severely versus mild-moderately demented nursing home patients. Aging (Milano)1998; 10:308-315.
26.
26. Ancoli-Israel S, Klauber MR, Jones DW, et al. Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients. Sleep1997; 20:18-23.
27.
27. Bliwise DL. Sleep apnea, APOE4 and Alzheimer’s disease: 20 years and counting?J Psychosom Res2002; 53:539-546.
28.
28. Liu RY, Zhou JN, van Heerikhuize J, et al. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotype. J Clin Endocrinol Metab1999; 84:323-327.
29.
29. Stopa EG, Volicer L, Kuo-LeBlanc V, et al. Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia. J Neuropathol Exp Neurol1999; 58:29-39.
30.
30. Skene DJ, Swaab DF. Melatonin rhythmicity: effect of age and Alzheimer’s disease. Exp Gerontol2003; 38:199-206.
