Background. Prior research indicates that heart failure (HF) patients exhibit significant cognitive deficits on neuropsychological testing. Sleep apnea is associated with both HF and reduced cognitive function, but the combined impact of these conditions on cognitive function is unknown. Methods. In the current study, 172 older adults with a dual diagnosis of HF and sleep apnea or HF alone completed a battery of cognitive tests measuring attention, executive functioning, and memory. Results. Relative to patients with HF alone, persons with both HF and sleep apnea performed worse on measures of attention after adjusting for demographic and medical variables. Conclusions. The current findings suggest that HF patients with comorbid sleep apnea may be at greater risk for cognitive impairment relative to HF patient without such history. Further work is needed to clarify mechanisms for these findings and to determine whether the interactive effects on cognitive function lead to poorer patient outcomes. 1. Introduction The American Heart Association estimates that heart failure (HF) affects more than five million adults and costs an estimated $30 billion annually in the United States alone [1]. As the population of older adults and the frequency of HF risk factors (e.g., hypertension and obesity) continue to rise, it is estimated that one in five adults will develop HF during their lifetime [1]. While the prevalence of this disease is alarming, so are the consequences—HF is a leading cause of hospitalization, morbidity, and mortality in the US [2–4]. HF is also a known risk factor for neurological disorders including Alzheimer’s disease, stroke, and vascular dementia [5–7]. However, it is now known that cognitive deficits begin to manifest long before patients are diagnosed with these more serious conditions. For example, recent studies have suggested that up to 75% of persons with HF exhibit deficits on testing, including reduced performance on tests of memory, attention, executive function, and language [8–11]. A growing number of contributors to cognitive impairment in persons with HF have been identified, including structural brain changes, reduced cerebral blood flow, and autonomic nervous system disruption [12–16]. Although not previously examined, it appears likely that sleep apnea is another important contributor. Sleep apnea is common in persons with HF and has an independent adverse impact on cognitive function [17–21]. Recent work has shown that persons with sleep apnea score poorly on measures of attention [20–23], memory retrieval [24, 25], and
References
[1]
American Heart Association, “Heart disease and stroke statistics—2011 update: a Report from the American Heart Association,” Circulation, vol. 123, pp. e18–e209, 2011.
[2]
R. Kahn, R. M. Robertson, R. Smith, and D. Eddy, “The impact of prevention on reducing the burden of cardiovascular disease,” Circulation, vol. 118, no. 5, pp. 576–585, 2008.
[3]
D. Lloyd-Jones, R. Adams, M. Carnethon, et al., “Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee,” Circulation, vol. 119, no. 3, pp. e21–181, 2009.
[4]
National Heart Lung and Blood Institute, Morbidity & Mortality: 2007 Chart Book on Cardiovascular, Lung, and Blood Diseases, National Heart Lung and Blood Institute, Bethesda, Md, USA, 2007.
[5]
C. Qiu, B. Winblad, A. Marengoni, I. Klarin, J. Fastbom, and L. Fratiglioni, “Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study,” Archives of Internal Medicine, vol. 166, no. 9, pp. 1003–1008, 2006.
[6]
G. C. Román, “Vascular dementia prevention: a risk factor analysis,” Cerebrovascular Diseases, vol. 20, no. 2, pp. 91–100, 2005.
[7]
T. J. Wang, J. M. Massaro, D. Levy et al., “A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study,” JAMA, vol. 290, no. 8, pp. 1049–1056, 2003.
[8]
O. P. Almeida and L. Flicker, “The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning,” Internal Medicine Journal, vol. 31, no. 5, pp. 290–295, 2001.
[9]
S. J. Bennett and M. J. Sauvé, “Cognitive deficits in patients with heart failure: a review of the literature,” The Journal of Cardiovascular Nursing, vol. 18, no. 3, pp. 219–242, 2003.
[10]
S. J. Pressler, U. Subramanian, D. Kareken et al., “Cognitive deficits in chronic heart failure,” Nursing Research, vol. 59, no. 2, pp. 127–139, 2010.
[11]
R. L. C. Vogels, P. Scheltens, J. M. Schroeder-Tanka, and H. C. Weinstein, “Cognitive impairment in heart failure: a systematic review of the literature,” European Journal of Heart Failure, vol. 9, no. 5, pp. 440–449, 2007.
[12]
S. J. Bennett, M. J. Sauvé, and R. M. Shaw, “A conceptual model of cognitive deficits in chronic heart failure,” Journal of Nursing Scholarship, vol. 37, no. 3, pp. 222–228, 2005.
[13]
S. Dimopoulos, M. Anastasiou-Nana, D. Sakellariou et al., “Effects of exercise rehabilitation program on heart rate recovery in patients with chronic heart failure,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 13, no. 1, pp. 67–73, 2006.
[14]
M. Garet, F. Degache, V. Pichot et al., “Relationship between daily physical activity and ANS activity in patients with CHF,” Medicine and Science in Sports and Exercise, vol. 37, no. 8, pp. 1257–1263, 2005.
[15]
G. C. Román, “Brain hypoperfusion: a critical factor in vascular dementia,” Neurological Research, vol. 26, no. 5, pp. 454–458, 2004.
[16]
T. Siachos, A. Vanbakel, D. S. Feldman, W. Uber, K. N. Simpson, and N. L. Pereira, “Silent strokes in patients with heart failure,” Journal of Cardiac Failure, vol. 11, no. 7, pp. 485–489, 2005.
[17]
L. Ayalon, S. Ancoli-Israel, A. A. Aka, B. S. McKenna, and S. P. A. Drummond, “Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task,” Sleep, vol. 32, no. 3, pp. 373–381, 2009.
[18]
L. Ferini-Strambi, C. Baietto, M. R. Di Gioia et al., “Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP),” Brain Research Bulletin, vol. 61, no. 1, pp. 87–92, 2003.
[19]
B. Naegele, V. Thouvard, J. L. Pepin et al., “Deficits of cognitive executive functions in patients with sleep apnea syndrome,” Sleep, vol. 18, no. 1, pp. 43–52, 1995.
[20]
S. Redline, M. E. Strauss, N. Adams et al., “Neuropsychological function in mild sleep-disordered breathing,” Sleep, vol. 20, no. 2, pp. 160–167, 1997.
[21]
M. L. Jackson, M. E. Howard, and M. Barnes, “Cognition and daytime functioning in sleep-related breathing disorders,” Progress in Brain Research, vol. 190, pp. 53–68, 2011.
[22]
F. Barbe, J. Pericas, A. Munoz et al., “Automobile accidents in patients with sleep apnea syndrome: an epidemiological and mechanistic study,” American Journal of Respiratory and Critical Care Medicine, vol. 158, no. 1, pp. 18–22, 1998.
[23]
M. C. Bedard, J. Montplaisir, F. Richer, I. Rouleau, and J. Malo, “Obstructive sleep apnea syndrome: pathogenesis of neuropsychological deficits,” Journal of Clinical and Experimental Neuropsychology, vol. 13, no. 6, pp. 950–964, 1991.
[24]
B. Na?gelé, S. H. Launois, S. Mazza, C. Feuerstein, J. L. Pépin, and P. Lévy, “Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory,” Sleep, vol. 29, no. 4, pp. 533–544, 2006.
[25]
A. Vakulin, S. D. Baulk, P. G. Catcheside et al., “Effects of moderate sleep deprivation and low-dose alcohol on driving simulator performance and perception in young men,” Sleep, vol. 30, no. 10, pp. 1327–1333, 2007.
[26]
S. Tregear, J. Reston, K. Schoelles, and B. Phillips, “Obstructive sleep apnea and risk of motor vehicle crash: systematic review and meta-analysis,” Journal of Clinical Sleep Medicine, vol. 5, no. 6, pp. 573–581, 2009.
[27]
P. O. Kiratli, A. U. Demir, B. Volkan-Salanci, B. Demir, and A. Sahin, “Cerebral blood flow and cognitive function in obstructive sleep apnea syndrome,” Hellenic Journal of Nuclear Medicine, vol. 13, no. 2, pp. 138–143, 2010.
[28]
M. E. Zimmemnan and M. S. Aloia, “A review of neuroimaging in obstructive sleep apnea,” Journal of Clinical Sleep Medicine, vol. 2, no. 4, pp. 461–471, 2006.
[29]
E. L. Teng and H. C. Chui, “The Modified Mini-Mental State (MMS) examination,” Journal of Clinical Psychiatry, vol. 48, no. 8, pp. 314–318, 1987.
[30]
R. M. Reitan, “Validity of the Trail Making Test as an indicator of organic brain damage,” Perceptual & Motor Skills, vol. 8, pp. 271–276, 1958.
[31]
B. Dubois, A. Slachevsky, I. Litvan, and B. Pillon, “The FAB: a frontal assessment battery at bedside,” Neurology, vol. 55, no. 11, pp. 1621–1626, 2000.
[32]
D. Wechsler, Manual for the Wechsler Adult Intelligence Scale, The Psychological Corporation, San Antonio, Tex, USA, 3rd edition, 1997.
[33]
C. J. Golden, The Stroop Color and Word Test: A Manual for Clinical and Experimental Uses, Stoelting, Chicago, Ill, USA, 1978.
[34]
R. J. Echemendia, M. R. Lovell, M. W. Collins, and G. P. Prigatano, “Return to play following mild traumatic brain injury: neuropsychology's role,” in Proceedings of the 107th Annual Meeting of the American Psychological Association, Washington, DC, USA, August 1999.
[35]
D. Delis, J. H. Kramer, E. Kaplan, and B. A. Ober, California Verbal Learning Test: Adult Version, The Psychological Corporation, San Antonio, Tex, USA, 1987.
[36]
R. E. Rikli and C. J. Jones, Senior Fitness Test Manual, Human Kinetics, Champaign, Ill, USA, 2001.
[37]
A. T. Beck, R. A. Steer, and G. K. Brown, BDI-II, Beck Depression Inventory: Manual, Harcourt Brace, Boston, Mass, USA, 2nd edition, 1996.
[38]
M. A. Woo, P. M. Macey, G. C. Fonarow, M. A. Hamilton, and R. M. Harper, “Regional brain gray matter loss in heart failure,” Journal of Applied Physiology, vol. 95, no. 2, pp. 677–684, 2003.
[39]
R. Schmidt, F. Fazekas, H. Offenbacher, J. Dusleag, and H. Lechner, “Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy,” Stroke, vol. 22, no. 2, pp. 195–199, 1991.
[40]
J. R. C. Almeida, T. C. T. F. Alves, M. Wajngarten et al., “Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study,” Brazilian Journal of Medical and Biological Research, vol. 38, no. 3, pp. 431–436, 2005.
[41]
T. C. T. F. Alves, J. Rays, R. Fráguas et al., “Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT,” Journal of Neuroimaging, vol. 15, no. 2, pp. 150–156, 2005.
[42]
M. L. Alosco, M. B. Spitznagel, R. Cohen et al., “Cognitive impairment is independently associated with reduced instrumental activities of daily living in persons with heart failure,” The Journal of Cardiovascular Nursing, vol. 27, no. 1, pp. 44–50, 2012.
[43]
L. L. Barclay, E. M. Weiss, S. Mattis, O. Bond, and J. P. Blass, “Unrecognized cognitive impairment in cardiac rehabilitation patients,” Journal of the American Geriatrics Society, vol. 36, no. 1, pp. 22–28, 1988.
[44]
M. A. Konstam, “Progress in heart failure management? Lessons from the real world,” Circulation, vol. 102, no. 10, pp. 1076–1078, 2000.
[45]
G. Zuccalà, C. Pedone, M. Cesari et al., “The effects of cognitive impairment on mortality among hospitalized patients with heart failure,” American Journal of Medicine, vol. 115, no. 2, pp. 97–103, 2003.
[46]
C. F. Salorio, D. A. White, J. Piccirillo, S. P. Duntley, and M. L. Uhles, “Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome,” Journal of Clinical and Experimental Neuropsychology, vol. 24, no. 1, pp. 93–100, 2002.
[47]
G. D. Greenberg, R. K. Watson, and D. Deptula, “Neuropsychological dysfunction in sleep apnea,” Sleep, vol. 10, no. 3, pp. 254–262, 1987.
[48]
H. C. Kim, T. Young, C. G. Matthews, S. M. Weber, A. R. Woodard, and M. Palta, “Sleep-disordered breathing and neuropsychological deficits: a population-based study,” American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 6, pp. 1813–1819, 1997.
[49]
I. Rouleau, A. Décary, A. J. Chicoine, and J. Montplaisir, “Procedural skill learning in obstructive sleep apnea syndrome,” Sleep, vol. 25, no. 4, pp. 401–411, 2002.
[50]
M. G. Fradley, M. G. Larson, S. Cheng et al., “Reference limits for N-terminal-pro-B-type natriuretic peptide in healthy individuals (from the Framingham Heart Study),” American Journal of Cardiology, vol. 108, no. 9, pp. 1341–1345, 2011.
[51]
W. Jiang, J. Alexander, E. Christopher, et al., “Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure,” Archives of Internal Medicine, vol. 162, no. 3, pp. 362–364, 2001.
[52]
T. Rutledge, V. A. Reis, S. E. Linke, B. H. Greenberg, and P. J. Mills, “Depression in heart failure. A meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes,” Journal of the American College of Cardiology, vol. 48, no. 8, pp. 1527–1537, 2006.
[53]
H. G. Koenig, “Depression in hospitalized older patients with congestive heart failure,” General Hospital Psychiatry, vol. 20, no. 1, pp. 29–43, 1998.
[54]
A. G. Wheaton, G. S. Perry, D. P. Chapman, and J. B. Croft, “Sleep disordered breathing and depression among U.S. adults: National health and nutrition examination survey, 2005–2008,” Sleep, vol. 35, no. 4, pp. 461–467, 2012.