The journal of nutrition, health & aging

, Volume 16, Issue 2, pp 134–137

Course of neuropsychiatric symptoms during a 4-year follow up in the REAL-FR cohort

  • S. Gonfrier
  • S. Andrieu
  • D. Renaud
  • B. Vellas
  • Ph. Robert
Course of Neuropsychiatric Symptoms During a 4-Year Follow Up in the real-FR Cohort



The multicenter PHRC REAL-FR cohort study was designed to follow community-dwelling patients with a diagnosis of Alzheimer’s Disease. The present study describes the evolution of neuropsychiatric symptoms (NPS) over 4 years.


686 patients were recruited at baseline from 16 French clinical centers. 151 patients were followed over the 4-year interval with 5 Neuropsychiatric evaluations. Neuropsychiatric symptoms were assessed using the Neuropsychiatric inventory (NPI). NPS symptoms were divided into 4 subgroups according to the European Alzheimer Disease Consortium NPI analysis; psychotic subgroup (hallucinations, delusions), hyperactivity subgroup (agitation, aggression, euphoria, disinhibition, irritability, aberrant motor behavior), apathy subgroup (apathy, eating) and affective subgroup (depression, anxiety). Secondly we studied the evolution of the population divided in 4 groups: Apathy only, Hyperactivity only, both Apathy and Hyperactivity, no Apathy no Hyperactivity.


At baseline, 100 patients (66%) presented with one or more clinically significant NPI symptoms. This figure increased to 88% at the end of 4-year follow-up (Linear by linear chi square, p<0, 0012). Five NPI symptoms showed significant increases in prevalence: agitation (17,9 to 29,1%), apathy (43,0 to 62,9%), disinhibition (2,6 to 14,6%), hallucination (2 to 4,6%) and aberrant motor behavior (13,9 to 29,1%). Prevalence of hyperactivity and apathy subgroups increased significantly during the follow-up while the prevalence of affective and psychotic subgroups did not. The number of patients with both apathy and hyperactivity increased (27% to 44%) during the follow-up period whereas the number of patients without these symptoms decreased (p =.009).


The present study shows that 2 types of symptoms increased primarily over time: Apathy and Hyperactivity. The coexistence of such opposite symptoms over time according to our result should be taken into consideration by clinicians treating those patients.

Key words

Alzheimer disease neuropsychiatric symptom cohort apathy hyperactivity 


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  1. 1.
    Steinberg M, Shao H, Zandi P, Lyketsos CG, Welsh-Bohmer KA, Norton MC, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 2008;23(2):170–177.PubMedCrossRefGoogle Scholar
  2. 2.
    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(12):2308–2314.PubMedGoogle Scholar
  3. 3.
    Aalten P, de Vugt ME, Jaspers N, Jolles J, Verhey FR. The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables. Int J Geriatr Psychiatry 2005;20(6):531–536.PubMedCrossRefGoogle Scholar
  4. 4.
    Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000;157(5):708–714.PubMedCrossRefGoogle Scholar
  5. 5.
    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(12):1475–1483.PubMedCrossRefGoogle Scholar
  6. 6.
    Mega MS, Cummings JL, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer’s disease. Neurology 1996;46(1):130–135.PubMedGoogle Scholar
  7. 7.
    Cummings JL, Schneider L, Tariot PN, Kershaw PR, Yuan W. Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease. Am J Psychiatry 2004;161(3):532–538.PubMedCrossRefGoogle Scholar
  8. 8.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189–198.PubMedCrossRefGoogle Scholar
  9. 9.
    Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP. A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2005;13(6):460–468.PubMedGoogle Scholar
  10. 10.
    Gaugler JE, Davey A, Pearlin LI, Zarit SH. Modeling caregiver adaptation over time: the longitudinal impact of behavior problems. Psychol Aging 2000;15(3):437–450.PubMedCrossRefGoogle Scholar
  11. 11.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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;34(7):939–944.PubMedGoogle Scholar
  12. 12.
    Gillette-Guyonnet S, Nourhashemi F, Andrieu S, Cantet C, Micas M, Ousset PJ, et al. The REAL.FR research program on Alzheimer’s disease and its management: methods and preliminary results. J Nutr Health Aging 2003;7(2):91–96.PubMedGoogle Scholar
  13. 13.
    Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9(3):179–186.PubMedCrossRefGoogle Scholar
  14. 14.
    Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist 1980;20(6):649–655.PubMedCrossRefGoogle Scholar
  15. 15.
    Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alzheimer’s disease treatments: a descriptive review. Alzheimers Dement 2008;4(1):49–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Cummings JL, Schneider E, Tariot PN, Graham SM. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006;67(1):57–63.PubMedCrossRefGoogle Scholar
  17. 17.
    Aalten P, Verhey FR, Boziki M, Bullock R, Byrne EJ, Camus V, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord 2007;24(6):457–463.PubMedCrossRefGoogle Scholar
  18. 18.
    Cummings JL. Behavioral and neuropsychiatric outcomes in Alzheimer’s disease. CNS Spectr 2005;10(11 Suppl 18):22–25.PubMedGoogle Scholar
  19. 19.
    Brodaty H, Draper B, Saab D, Low LF, Richards V, Paton H, et al. Psychosis, depression and behavioural disturbances in Sydney nursing home residents: prevalence and predictors. Int J Geriatr Psychiatry 2001;16(5):504–512.PubMedCrossRefGoogle Scholar
  20. 20.
    Snowdon J, Miller R, Vaughan R. Behavioural problems in Sydney nursing homes. Int J Geriatr Psych 1996;11:535–541.CrossRefGoogle Scholar
  21. 21.
    Sourai R, McCusker J, Cole M, Abrahamowicz M. Agitation in demented patients in an acute care hospital: prevalence, disruptiveness and staff burden. Int Psychogeriatr 2001;13:183–197.Google Scholar
  22. 22.
    Robert PH, Verhey FR, Byrne EJ, Hurt C, De Deyn PP, Nobili F, et al. Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer disease consortium. Eur Psychiatry 2005;20(7):490–496.PubMedCrossRefGoogle Scholar
  23. 23.
    Benoit M, Staccini P, Brocker P, Benhamidat T, Bertogliati C, Lechowski L, et al. [Behavioral and psychologic symptoms in Alzheimer’s disease: results of the REAL.FR study]. Rev Med Interne 2003;24Suppl 3:319s–324s.PubMedCrossRefGoogle Scholar
  24. 24.
    Benoit M, Robert P. [Clinical and neurophysiological aspects of depression and apathy]. Encephale 2007;33(Pt 3):853–855.PubMedCrossRefGoogle Scholar
  25. 25.
    Eustace A, Coen R, Walsh C, Cunningham CJ, Walsh JB, Coakley D, et al. A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer’s disease. Int J Geriatr Psychiatry 2002;17(10):968–973.PubMedCrossRefGoogle Scholar
  26. 26.
    Devanand DP, Jacobs DM, Tang MX, Del Castillo-Castaneda C, Sano M, Marder K, et al. The course of psychopathologic features in mild to moderate Alzheimer disease. Arch Gen Psychiatry 1997;54(3):257–263.PubMedCrossRefGoogle Scholar
  27. 27.
    Haupt M, Kurz A, Janner M. A 2-year follow-up of behavioural and psychological symptoms in Alzheimer’s disease. Dement Geriatr Cogn Disord 2000;11(3):147–152.PubMedCrossRefGoogle Scholar
  28. 28.
    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(11):1438–1443.PubMedGoogle Scholar
  29. 29.
    Marin RS, Firinciogullari S, Biedrzycki RC. The sources of convergence between measures of apathy and depression. J Affect Disord 1993;28(1):7–14.PubMedCrossRefGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2012

Authors and Affiliations

  • S. Gonfrier
    • 1
  • S. Andrieu
    • 2
    • 3
  • D. Renaud
    • 4
  • B. Vellas
    • 5
  • Ph. Robert
    • 4
  1. 1.C.H.U NiceNiceFrance
  2. 2.Toulouse University HospitalToulouseFrance
  3. 3.UMR1027 INSERM-Université Paul SabatierToulouseFrance
  4. 4.CMRR NiceNiceFrance
  5. 5.Toulouse University HospitalToulouseFrance

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