Journal List > Dement Neurocogn Disord > v.13(2) > 1120725

Kwak, Yang, and Koo: Depression in Alzheimer's Disease

Abstract

Depression is one of the most common psychiatric complications of Alzheimer disease (AD), affecting from 30% to 50% of prevalence, with most estimates in the 20-30% range. Because of having a presentation in the context of AD that differs from typical early-onset depression, it is not easy one to detect and quantify reliably, and can be difficulty to differentiate depression from the other neuropsychiatric symptoms of AD. Due to the lack of large randomized trials, optimal treatment and the true degree of efficacy remains undetermined. However, these treatments can reduce adverse impact of depression on patients and caregivers. This article provides a practical discussion of the diagnosis, evaluation, differential diagnosis and treatment of depression in AD for the clinician.

Figures and Tables

Table 1
Provisional diagnostic criteria for depression of AD
dnd-13-27-i001

Notes

We have no conflicts of interests.

References

1. Devier DJ, Villemarette-Pittman N, Brown P, Pelton G, Stern Y, Sano M, et al. Predictive utility of type and duration of symptoms at initial presentation in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2010; 30:238–244.
crossref
2. Wilson RS, Mendes De Leon CF, Bennet DA, Bienias JL, Evans DA. Depressive symptoms and cognitive decline in a community population of older persons. J Neurol Neurosurg Psychiatry. 2004; 75:126–129.
3. Devanand DP, Sano M, Tang Mx, Taylor S, Gurland BJ, Wilder D, et al. Depressed mood and the incidence of Alzheimer's disease in elderly living in the community. Arch Gen Psychiatry. 1996; 53:175–182.
crossref
4. Wilson RS, Barnes LL, Mendes De Leon CF, Aggarwal NT, Schneider JS, Bach J, et al. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology. 2002; 59:364–370.
crossref
5. Fuhrer R, Dufouil C, Dartigues JF. PAQUID Study. Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study. J Am Geriatr Soc. 2003; 51:1055–1063.
crossref
6. Gonzáles-Salvador T, Lyketsos CG, Baker AS, Roques C, Hovanek L, Steele CD, et al. Quality of life of patients with dementia in long-term care. Int J Geriatr Psychiatry. 2000; 15:181–189.
7. Harwood DG, Barker WW, Ownby RL, Duara R. Association between premorbid history of depression and current depression in Alzheimer's disease. J Geriatr Psychiatry Neurol. 1999; 12:72–75.
crossref
8. Lyketsos CG, Steele C, Galik E, Rosenblatt A, Steinberg M, Warren A, et al. Physical aggression in dementia patients and its relationship to depression. Am J Psychiatry. 1999; 156:66–71.
crossref
9. Gonzáles-Salvador MT, Aragano C, Lyketsos CG, Barba AC. The stress and psychological morbidity of the Alzheimer patient caregiver. Int J Geriatr Psychiatry. 1999; 14:701–710.
crossref
10. Steele C, Rovner B, Chase GA, Folstein M. Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. Am J Psychiatry. 1990; 147:1049–1051.
crossref
11. Lyketsos CG, Baker L, Warren A, Steele C, Brandt J, Steinberg M, et al. Major and minor depression in Alzheimer's disease: prevalence and impact. J Neuropsychiatry Clin Neurosci. 1997; 9:556–561.
crossref
12. Weiner MF, Doody RS, Sairam R, Foster B, Liao TY. Prevalence and incidence of major depressive disorder in Alzheimer's disease: findings from two databases. Dement Geriatr Cogn Disord. 2002; 13:8–12.
crossref
13. Forsell Y, Winblad B. Major depression in a population of demented and nondemented old people: prevalence and correlates. J Am Geriatr Soc. 1998; 46:27–30.
crossref
14. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002; 288:1475–1483.
crossref
15. Payne JL, Sheppard JM, Steinberg M, Warren A, Baker A, Steele C, et al. Incidence, prevalence, and outcomes of depression in residents of a long term care facility with dementia. Int J Geriatr Psychiatry. 2002; 17:247–253.
crossref
16. Teng E, Lu PH, Cummings JL. Neuropsychiatric symptoms are associated with progression from mild cognitive impairment toAlzheimer's disease. Dement Geriatr Cogn Disord. 2007; 24:253–259.
crossref
17. Levy ML, Cummings JL, Fairbanks LA, Bravi D, Calvani M, Carta A. Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry. 1996; 153:1438–1443.
crossref
18. Olin JT, Katz IR, Meyers BS, Schneider LS, Lebowitz BD. Provisional diagnostic criteria for depression of Alzheimer disease: rationale and background. Am J Geriatr Psychiatry. 2002; 10:129–141.
crossref
19. Holtzer R, Scarmeas N, Wegesin DJ, Albert M, Brandt J, Dubois B. Depressive symptoms in Alzheimer's disease: natural course and temporal relation to function and cognitive status. J Am Geriatr Soc. 2005; 53:2083–2089.
crossref
20. Wilson RS, Hoganson GM, Rajan KB, Barnes LL, Mendes de Leon CF, Evans DA. Temporal course of depressive symptoms during the development of Alzheimer disease. Neurology. 2010; 75:21–26.
crossref
21. Kwak YT, Yang Y, Pyo SJ, Koo MS. Clinical characteristics according to depression screening tools in patients with Alzheimer's disease: view from self, caregiver-reported and drug-intervention pattern. Geriatr Gerontol Int. 2013; 13:701–707.
crossref
22. Kwak YT, Yang Y, Kwak SG. Clinical characteristics of behavioral and psychological symptoms in patients with drug-naive Alzheimer's disease. Dement Neurocognitive Disord. 2012; 11:87–94.
crossref
23. Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R. Depressive symptoms and risk of dementia: the Framingham Heart Study. Neurology. 2010; 75:35–41.
crossref
24. Andersen K, Lolk A, Kragh-Sørensen P, Petersen NE, Green A. Depression and the risk of Alzheimer disease. Epidemiology. 2005; 16:233–238.
crossref
25. Gatz JL, Tyas SL, St John P, Montgomery P. Do depressive symptoms predict Alzheimer's disease and dementia? J Gerontol A Biol Sci Med Sci. 2005; 60:744–747.
crossref
26. Chen R, Hu Z, Wei L, Qin X, McCracken C, Copeland JR. Severity of depression and risk for subsequent dementia: cohort studies in China and the UK. Br J Psychiatry. 2008; 193:373–377.
crossref
27. Byers AL, Covinsky KE, Barnes DE, Yaffe K. Dysthymia and depression increase risk of dementia and mortality among older veterans. Am J Geriatr Psychiatry. 2012; 20:664–672.
crossref
28. Irie F, Masaki KH, Petrovitch H, Abbott RD, Ross GW, Taaffe DR, et al. Apolipoprotein E epsilon4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia Aging Study. Arch Gen Psychiatry. 2008; 65:906–912.
crossref
29. Geerlings MI, Schmand B, Braam AW, Jonker C, Bouter LM, van Tilburg W. Depressive symptoms and risk of Alzheimer's disease in more highly educated older people. J Am Geriatr Soc. 2000; 48:1092–1097.
crossref
30. Becker JT, Chang YF, Lopez OL, Dew MA, Sweet RA, Barnes D. Depressed mood is not a risk factor for incident dementia in a community-based cohort. Am J Geriatr Psychiatry. 2009; 17:653–663.
crossref
31. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, et al. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002; 156:445–453.
crossref
32. Vinkers DJ, Gussekloo J, Stek ML, Westendorp RG, van der Mast RC. Temporal relation between depression and cognitive impairment in old age: prospective population based study. BMJ. 2004; 329:881.
crossref
33. Amieva H, Le Goff M, Millet X, Orgogozo JM, Peres K, Barberguer-Gateau P, et al. Prodromal Alzheimer's disease: sucessive emergence of the clinical symptoms. Ann Neurol. 2008; 64:492–498.
crossref
34. Dal Forno G, Palermo MT, Donohue JE, Karagiozis H, Zonderman AB, Kawas CH. Depressive symptoms, sex, and risk for Alzheimer's disease. Ann Neurol. 2005; 57:381–387.
crossref
35. Dotson VM, Beydoun MA, Zonderman AB. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology. 2010; 75:27–34.
crossref
36. Barnes DE, Yaffe K, Byers AL, McCormick M, Schaefer C, Whitmer RA. Mid-life versus late-life depressive symptoms and risk of dementia: differential effects for Alzheimer's disease and vascular dementia. Arch Gen Psychiatry. 2012; 69:493–498.
37. Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol. 2003; 60:753–759.
38. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision. Washington, DC: American Psychiatric Press;2000.
39. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23:56–62.
crossref
40. Zubenko GS, Zubenko WN, McPherson S, Spoor E, Marin DB, Farlow MR, et al. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Am J Psychiatry. 2003; 160:857–866.
crossref
41. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988; 23:271–284.
crossref
42. Olin JT, Schneider LS, Katz IR, Meyers BS, Alexopoulos GS, Breitner JC, et al. Provisional diagnostic criteria for depression of Alzheimer's disease. Am J Geriatr Psychiatry. 2002; 10:125–128.
43. Teng E, Ringman JM, Ross LK, Mulnard RA, Dick MB, Bartzokis G, et al. Diagnosing depression in Alzheimer's disease with the national institute of mental health provisional criteria. Am J Geriatr Psychiatry. 2008; 16:469–477.
crossref
44. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4:561–571.
crossref
45. Debruyne H, Van Buggenhout M, Le Bastard N, Aries M, Audenaert K, De Deyn PP, et al. Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment? Int J Geriatr Psychiatry. 2009; 24:556–562.
crossref
46. Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas A. Behavioral symptoms in Alzheimer's disease: phenomenology and treatment. J Clin Psychiatry. 1987; 48:9–15.
47. Tariot PN, Mack JL, Patterson MB. The behavior rating scale for dementia of the Consortium to establish a Registry for Alzheimer's disease. Am J Psychiatry. 1995; 152:1349–1357.
48. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology. 1994; 44:2308–2314.
crossref
49. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983; 17:37–49.
crossref
50. Heun R, Kockler M, Ptok U. Depression in Alzheimer's disease: is there a temporal relationship between the onset of depression and the onset of dementia? Eur Psychiatry. 2002; 17:254–258.
crossref
51. Cummings JL, Back C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease. Am J Geriatr Psychiatry. 1998; 6:S64–S78.
crossref
52. Whitford GM. Alzheimer's disease and serotonin: a review. Neuropsychobiology. 1986; 15:133–142.
crossref
53. Meltzer CC, Smith G, DeKosky ST, Pollock BG, Mathis CA, Moore RY, et al. Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging role of functional imaging. Neuropsychopharmacology. 1998; 18:407–430.
crossref
54. Gareri P, De Fazio P, Sarro G. Neuropharmacology of depression in aging and age-related diseases. Ageing Res Rev. 2002; 1:113–134.
crossref
55. Forstl H, Burns A, Luthert P. Clinical and neuropathological correlates of depression in Alzheimer's disease. Psychol Med. 1992; 22:877–884.
crossref
56. Zubenko GS. Biological correlates of clinical heterogeneity in primary dementia. Neuropsychopharmacology. 1992; 6:77–93.
57. Zweig RM, Ross CA, Hedreen JC, Steele C, Cardillo JE, Whitehouse PJ, et al. The neuropathology of aminergic nuclei in Alzheimer's disease. Ann Neurol. 1988; 24:233–242.
crossref
58. Palmer AM, Stratmann GC, Procter AW, Bowen DM. Possible neurotransmitter basis of behavioral changes in Alzheimer's disease. Ann Neurol. 1988; 23:616–620.
crossref
59. Zubenko GS, Moossy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol. 1990; 47:209–214.
crossref
60. Blin J, Baron JC, Dubois B, Crouzel C, Fiorelli M, Attar-Lévy D, et al. Loss of brain 5HT2 receptors in Alzheimer's disease: In vivo assessment with positron emission tomography and 18F setoperone. Brain. 1993; 116:497–510.
61. Rapp MA, SchneiderBeeri M, Purohit DP, Perl DP, Haroutunian V, Sano M. Increased neurofibrillary tangles in patients with Alzheimer's disease with comorbid depression. Am J Geriatr Psychiatry. 2008; 16:168–174.
crossref
62. Wilson RS, Schneider JA, Bienias JL, Arnold SE, Evans DA, Bennet DA. Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons. Neurology. 2003; 61:1102–1107.
crossref
63. Teri L, Logsdon RG, Uomoto J, McCurry SM. Behavioral treatment of depression in dementia patients: a controlled clinical trial. J Gerontol B Psychol Sci Soc Sci. 1997; 52:P159–P166.
crossref
64. Teri L, Gibbons LE, McCurry SM, Logsdon RG, Buchner DM, Barlow WE, et al. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003; 290:2015–2022.
crossref
65. DeRubeis RJ, Hollon SD, Amsterdam JD, Shelton RC, Young PR, Salomon RM, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression. Arch Gen Psychiatry. 2005; 62:409–416.
crossref
66. Hollon SD, DeRubeis RJ, Shelton RC, Amsterdam JD, Salomon RM, O'Reardon JP, et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry. 2005; 62:417–422.
crossref
67. Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, Munro C, Baker AS, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003; 60:737–746.
68. Petracca G, Tesón A, Chemerinski E, Leiguarda R, Starkstein SE. A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. J Neuropsychiatry Clin Neurosci. 1996; 8:270–275.
crossref
69. Fuchs A, Hehnke U, Erhart C, Schell C, Pramshohler B, Danninger B, et al. Video rating analysis of effect of maprotiline in patients with dementia and depression. Pharmacopsychiatry. 1993; 26:37–41.
crossref
70. Roth M, Mountjoy CQ, Amrein R. Meclobemide in elderly patients with cognitive decline and depression. An international double-blind, placebo-controlled trial. Br J Psychiatry. 1996; 168:149–157.
crossref
71. Nyth AL, Gottfries CG. The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. A Nordic multicentre study. Br J Psychiatry. 1990; 157:894–901.
crossref
72. Rosenberg PB, Drye LT, Martin BK, Martin BK, Frangakis C, Mintzer JE, et al. Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry. 2010; 18:136–145.
crossref
73. Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet. 2011; 378:403–411.
crossref
74. de Vasconcelos Cunha UG, Lopes Rocha F, Avila de Melo R, Alves Valle E, de Souza Neto JJ, Mendes Brega R, et al. A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia. Dement Geriatr Cogn Disord. 2007; 24:36–41.
crossref
75. Reifler BV, Teri L, Raskind M, Veith R, Barnes R, White E, et al. Double-blind trial of Imipramine in Alzheimer's disease patients with and without depression. Am J Psychiatry. 1989; 146:45–49.
crossref
76. Petracca GM, Chemerinski E, Starkstein SE. A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease. Int Psychogeriatr. 2001; 13:233–240.
crossref
77. Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011; 59:577–585.
crossref
78. Lyketsos CG, Sheppard JM, Steele CD, Kopunek S, Steinberg M, Baker AS, et al. Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the depression in Alzheimer's disease study. Am J Psychiatry. 2000; 157:1686–1689.
crossref
79. Petracca GM, Chemerinski E, Starkstein SE. A doubleblind placebo-controlled study of Fluoxetine in depressed patients with Alzheimer's disease. Int Psychogeriatr. 2001; 13:233–240.
crossref
80. Munro CA, Brandt J, Sheppard JM, Steele CD, Samus QM, Steinberg M, et al. Cognitive response to pharmacological treatment for depression in Alzheimer disease: secondary outcomes from the depression in Alzheimer's disease study (DIADS). Am J Geriatr Psychiatry. 2004; 12:491–498.
crossref
81. Cummings JL, Schneider L, Tariot PN, Kershaw PR, Weiying Y. Reduction of behavioural disturbances and caregiver distress by galantamine in patients with Alzheimer's disease. Am J Psychiatry. 2004; 161:532–538.
crossref
82. Gauthier S, Feldman H, Hecker J, Vellas B, Emir B, Subbiah P. Donepezil MSAD study investigators group. Functional, cognitive, and behavioral effects of donepezil in patients with moderate Alzheimer's disease. Curr Med Res Opin. 2002; 18:347–354.
crossref
83. Mega MS, Masterman DM, O'Connor SM, Barclay TR, Cummings JL. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol. 1999; 56:1388–1393.
crossref
84. Pinheiro D. Anticonvulsantmood stabilizers in the treatment of behavioral and psychological symptoms of dementia (BPSD). Encephale. 2008; 34:409–415.
85. Sultzer DL, Davis SM, Tariot PN, Dagerman KS, Lebowitz BD, Lyketsos CG, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: Phase 1 outcomes from the CATIEAD effectiveness trial. Am J Psychiatry. 2008; 165:844–854.
crossref
86. Rao V, Lyketsos CG. The benefits and risks of ECT for patients with degenerative dementia who also suffer from depression. Int J Geriatr Psychiatry. 2000; 15:729–735.
crossref
87. Rabins PV, Lyketsos CG, Steele CD. Practical dementia care. New York: Oxford University Press;1999.
88. Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J Clin Psychiatry. 1999; 60:107–115.
crossref
89. Tariot PN, Erb R, Podgorski CA, Cox C, Patel S, Jakimovich L, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry. 1998; 155:54–61.
crossref
90. Porsteinsson AP, Tariot PN, Erb R, Cox C, Smith E, Jakimovich L, et al. Placebo-controlled study of divalproex sodium for agitation in dementia. Am J Geriatr Psychiatry. 2001; 9:58–66.
crossref
TOOLS
Similar articles