Abstract
The rate of cognitive decline in Alzheimer’s disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different “a priori” definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.
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Abbreviations
- AD:
-
Alzheimer’s disease
- RCD:
-
Rapid cognitive decline
- CGA:
-
comprehensive geriatric assessment
- RF:
-
risk factors
- MMSE:
-
Mini-Mental State Examination
- AchEIs:
-
Acetylcholinesterase inhibitors
- ADAS-cog:
-
Alzheimer’s disease Assessment Scale cognitive component
- HR:
-
Hazard ratio
- ADL:
-
Activity of daily living
- MNA:
-
Nutritional Assessment
- EPS:
-
extrapyramidal signs
- DLB:
-
Lewy Body dementia
- CDR:
-
Clinical Dementia Rating
- CVRF:
-
cardiovascular risk factors
- ApoE ɛ4:
-
Apolipoprotein E (4)
- BuChE:
-
Butyrylcholinesterase
- MRI:
-
magnetic resonance imaging
- rCBF:
-
regional cerebral blood flow
- SD:
-
standard deviation
- CSF:
-
cerebrospinal fluid
- WMH:
-
white matter hyperintensity
- Abeta1-42:
-
amyloid beta 1-42
- t-tau:
-
total tau protein
References
Holmes C, Lovestone S. Long-term cognitive and functional decline in late onset Alzheimer’s disease: therapeutic implications. Age and Aging 2003;32:200–204
Folstein MF, Folstein SE, Mc Hugh PR. Mini-Mental-Test: a practical method for grading the cognitive state of patient for the clinician. J Psychiatr Res 1975; 12: 189–198
Morris JC, Edland S, Clark C et al. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer’s disease. Neurology 1993;43:2457–2465.
Cortes F, Gillette-Guyonnet S, Nourhashemi F et al. Recent Data on the natural history of Alzheimer disease: Results from the REAL.FR study. J Nutr Health Aging 2005;9:86–94
Kraemer HC, Tinklenberg J, Yesavage JA. “How far” vs “how fast” in Alzheimer’s disease. Arch Neurol 1994;51:275–79
Hui JS, Wilson RS, Bennett DA et al. Rate of cognitive decline and mortality in Alzheimer’s disease. Neurology 2003;61:1356–1361
Dumont C, Voisin T, Nourhashemi F et al. Predictive factors for rapid loss on the Mini-Mental State Examination in Alzheimer’s disease. J Nutr Health Aging 2005;9:163–167
Holtzer R, Wegesin D, Albert S et al. The rate of cognitive decline and risk of reaching clinical milestones in Alzheimer’s disease. Arch Neurol 2003;60:1137–1142.
Doody RS, Massman P, Dunn K. A method for estimating progression rates in Alzheimer’s disease. Arch Neurol 2001;58:449–454
O’Hara R, Thompson JM, Kraemer HC et al. Which Alzheimer patients are at risk for rapid cognitive decline? J Geriatr Psychiatry Neurol 2002;15:233–238
Atchinson TB, Bradshaw M, Massman PJ. Investigation of profile difference between Alzheimr’s disease patients declining at different rates: Examination of baseline neuropsychological data. Arch Clin Neuropsychol 2004;19:1007–1015
Helmer C, Andrieu S, Pérès K, Orgogozo JM, Vellas B, Dartigues JF. Predictive value of decline in ADAS-cog for survival without severe Alzheimer’s disease. Dement Geriatr Cogn Disor 2007:168–174
Gauthier S, Vellas B, Farlow M, Burn D. Aggressive course of disease in dementia. Alzheimer’s and Dementia. 2006;2:210–217
Dumont C, Gillette-Guyonnet S, Andrieu S, Cantet C, Ousset PJ, Vellas B, groupe REAL.FR. Baisse rapide du Mini-Mental State Examination: etude REAL.FR. Rev Med Int 2003;24:345s-350s
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–1364
Farlow MR, Hake A, Messina J et al. Response of patients with Alzheimer’s disease to rivastigmine treatment is predicted by the rate of disease progression. Arch Neurol 2001;58:417–422
Farlow MR, Small GW, Quarg P, Krause A. Efficacy of rivastigmine in Alzheimer’s disease patients with rapid disease progression: Results of a meta-analysis. Dement Geriatr Cogn Disord 2005;20:192–197
Wilkinson D, Andersen HF. Analysis of the effect of memantine in reducing the worsening of clinical symptoms in patients with moderate to severe Alzheimer’s disease. Dement Geriatr Cogn Disord 2007;24:138–145
Soto ME, Gillette-Guyonnet S, Vellas B, the REAL.FR group. Rapid cognitive decline: searching for a definition and predictive factor among elderly with Alzheimer’s disease. J Nutr Health Aging 2005;9:158–161
Clark CM, Sheppard L, Fillenbaum CG, et al. Variability in annual Mini-Mental State Examination score in patients with probable Alzheimer’s disease: a clinical perspective of data from the Consortium to Establish a Registry for Alzheimer’s disease. Arch Neurol 1999;56:857–862
Carcaillon L, Pèrès K, Péré JJ, Helmer C, Orgogozo JM, Dartigues JF. Fast cognitive decline at the time of dementia diagnosis: a major prognostic factor for survival in the community. Dement Geriatr Cogn Disord 2007;23:439–445
Soto ME, Andrieu S, Cantet C et al. Predictive Value of Rapid Decline in Mini-Mental State Examination in Clinical Practice for Prognosis in Alzheimer’s disease. Dement Geriatr Cogn Disord 2008;26:109–116
Capitani E, Cazzaniga R, Francescani A, Spinnler H. Cognitive deterioration in Alzheimer’s disease: is the early course predictive of the later stages? Neurol Sci 2004;25:198–204
Noda A, MS, Kraemer H, Taylor JL, Schneider B, Ashford JW, Yesavage JA. Strategies to reduce site differences in multisite studies: a case study of Alzheimer disease progression. Am J Geriatr Psyquiatry 2006;14:931–938
Jacobs D, Sano M, Marder K et al. Age at onset on Alzheimer’s disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology 1990;40:8–14
Ho GJ, Hansen LA, Alford MF et al. Age at onset is associated with disease severity in Lewy body variant and in Alzheimer’s disease. Neuroreport 2002;13:1825–1828
Stern Y, Alexander GE, Prohovnik I, Mayeaux R. Inverse relation-ship between education and parietotemporal perfusion deficit in Alzheimer’s disease. Ann Neurol 1992;32:371–375.
Teri L, McCurry SM, Edland SD et al. Cognitive decline in Alzheimer’s disease: a longitudinal investigation of risk factors for accelerated decline. J Gerontol A Biol Sci Med Sci 1995;50:M49-M55
Stern Y, Albert S, Tang MX, Tsai WY. Rate of memory decline in AD is related to education and occupation: Cognitive reserve? Neurology 1999;53:1942–1947
Hall CB, Derby C, Le Valley A, Katz MJ, Verguese J, Lipton RB. Education delays accelerated decline on a memory test in persons who develop dementia. Neurology 2007 69:1657–1664
Guk-Hee Suh, Young-Su Ju, Byeong Kil Yeon, Ajit Shah. A longitudinal study of Alzheimer’s disease: rates of cognitive decline and functional decline. Int J Geriatr Psy 2004;19:817–824
Wilson R, McCann J, Li Yan, Aggarwal N, Gilley D, Evans D. Nursing home placement, day care use, and cognitive decline in Alzheimer’s disease. Am J Psychiatry 2007;164:910–915
Kaufman Y, Anaki D, Binns M, Freedman M. Cognitive decline in Alzheimer’s disease: impact of spirituality, religiosity, and QOL. Neurology 2007 68:1509–1514
Ousset PJ, Nourhashemi F, Reynish E, Vellas B. Nutritional status is associated with disease progression in very mild Alzheimer’s disease. Alz Dis Assoc Disord. 2008;22:66–71
Chui HC, Lyness SA, Sobel E, Schneider LS. Extrapiramidal signs and psychiatric symptoms predict faster cognitive decline in Alzheimer’s disease. Arch Neurol 1994;51:676–681
Miller TP, Tinklenberg JR, Brooks JO, Yesavage JA. Cognitive decline in patients with Alzheimer’s disease: differences in patients with and without extrapiramidal signs. Alzheimer Dis 1991;5:251–256
Lopez OL, Wisnieski SR, Becker JT, Boller F, Dekosky ST.. Extrapiramidal signs in patients with probable Alzheimer’s disease. Arch Neurol 1997;54:969–975
Scarmeas N, Hadjigeorgiou GM, Papadimitriou A et al. Motor signs during course of Alzheimer’s disease. Neurology 2004;63:975–982
Capitani E, Francescani A, Spinner H. Are hallucinations and extrapiramidal signs associated with a steeper cognitive decline in degenerative dementia patients? Neurol Sci 2007;28:245–250
Kraybill MI, Larson EB, Tsuang DW, Teri L. McCormick WC, Bowen JD et al. Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both. Neurology 2005;64:2069–2073
Marra C, Silveri Maria C, Gainotti G. Predictors of cognitive decline in the early stage of probably Alzheimer’s disease. Dement Geriatr Cogn Disord 2000; 11:212–218
Buccione R, Perri R, Carlesimo A, Fadda L, Serra L, Scalmana S, Caltagirone. Cognitive and behavioural predictors of progression rates in Alzheimer’s disease. European Journal of Neurology. 2007;14:1468–1331
Shaufele M, Bickel H, Weyerer S. Which factors influence cognitive decline in older adults suffering from dementing disorders?. Int J Geriatr Pychiatry 2002;17:1055–1063
Coen RF, Maguire C, Swanwick GR, Kirby M, Burke T, Lawlor BA, et al. Letter and category fluency in Alzheimer’s disease: a prognosis indicator of progression. Dementia 1996;7:246–250
Beatty WW, Salmon DP, Tröster AI, Tivis RD. Do primary and secondary measures of semantic memory predict cognitive decline in Alzheimer’s disease? Aging, Neuropsychology, and Cognition 2002;9:1–10
Wilson RS, Tang Y, Aggarwal NT, Gilley DW, McCann JJ, Bienias JL, Evans DA. Hallucinations, cognitive decline, and death in Alzheimer’s disease. Neuroepidemiology 2005;26:68–75
Mortimer JA, Ebbit B, Jun SP et al. Predictors of cognitive and functional progression in patients with Alzheimer’s disease. Neurology 1992;42:1689–1696
Scarmeas N, Brandt J, Blacker D et al. Disruptive behavior as a predictor in Alzheimer Disease. Arch Neurol 2007;64 1755–1761
Bhargava D, Weiner M, Hynan L, Diaz-Arrastia R, Lipton A. Vascular disease and risk factors, rate of progression, and survival in Alzheimer’s disease. J Geriatr Psychiatry Neurol 2006;19:78–82
Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology 2006;67:1357–1361
Abellan G, Rolland Y, Nourhashémi F, Cantet C, Andrieu S, Vellas B. Cardiovascular risk factors and progression of Alzheimer’s disease. Alz Dis Assoc Disord. In press
Mielke MM, Rosenberg PB, Tschanz J et al. Vascular factors predict rate of progression in Alzheimer disease. Neurology 2007;69:1850–1858
Anstey KJ, von Sanden C, Salim A, O’Kearney R. Smoking as a risk for dementia and cognitive decline: a meta-analyses of prospective studies. Am J Epidemiol, 2007;166:367–378
Lane R, Farlow M. Lipid homeostasis and apolipoprotein E in the development and progression in Alzheimer’s disease. J Lipid Res 2005;46:949–968
Consentino S, Scarmeas N, Helzner E et al. APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease. Neurology, 2008;70:1842–1849
Holmes C. Genotype and phenotype in Alzheimer’s disease. Br J Psy 2002;180:131–134
Martins CAR, Oulhaj A, de Jager CA, Williams JH. APOE alleles predict the rate of cognitive decline in Alzheimer’s disease. Neurology 2005;65:1888–1893
Holmes C, Ballard C, Lehman D, David S, Beaumont H, Day IN, et al. Rate of progression of cognitive decline in Alzheimer’s disease: Effect of butyrylcholinesterase K gene variation. J Neurol Neurosurg Psychiatry 2005; 76:640–643
O’Brien KK, Saxby BK, Ballard CG et al. Regulation of attention and response to therapy in dementia by butyrylcholinesterase. Pharmacogenetics 2003;13:231–239
Jack CR Jr, Shiung MM, Gunter JL, et al RC. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology. 2004 24;62:591–600
Kinkingnéhun S, Sarazin M, Lehéricy, Guichart-Gomez E, Hergueta T, Dubois B. VBM anticipates the rate of progression of Alzheimer disease: a 3-year longitudinal study. Neurology 2008;70:2201–2211
Capizzano AA, Acion L, Bekinschtein T, Furman M, Gomila H, Martinez A, Mizrahi R, Starkstein SE. White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2004 Jun;75 (6):822–7.
Brickman AM, Honig LS, Scarmeas N et al. Measuring cerebral atrophy and white matter hyperintensity burden predict the rate of cognitive decline in Alzheimer disease. Arch Neurol. 2008;65:1202–1208
Nagahama Y, Nabatame H, Okina T et al. Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer’s disease.Eur Neurol 2003;50:1–9
Stefani A, Martorana A, Bernardini S et al. CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment. J Neurol Sci. 2006;251:124–128
Huey ED, Mirza N, Putnam KT, et al. Stability of CSF beta-amyloid (1–42) and tau levels by APOE genotype in Alzheimer disease patients. Dement Geriatr Cogn Disord. 2006;22:48–53
Locascio JJ, Fukumoto H, Yap L et al. Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease; Arch Neurol; 2008;65:776–785
Gillette-Guyonnet S, Andrieu S, Cortes F, et al. Outcome of Alzheimer’s disease potential impact of cholinesterase inhibitors. J Gerontol A Biol Sci Med Sci. 2006;61:516–20
Fillit HM, Doody RS, Binaso K, Crooks GM, Ferris SH, Farlow MR, Leifer B, Mills C, Minkoff N, Orland B, Reichman WE, Salloway S. Recommendations for best practices in the treatment of Alzheimer’s disease in managed care. Am J Geriatr Pharmacother 2006;4 Suppl A:S9-S24
Nourhashémi F, Gillette S, Andrieu S. Managing Alzheimer’s disease: global care and support program. Rev Prat. 2005;55:1903–1911
California Workgroup on guidelines for Alzheimer’s Disease Management. Guidelines for Alzheimer’s disease management. 2002
Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L et al. Guidelines for managing Alzheimer’s disease: part II. Treatment. Am Fam Physician 2002;65:2525–2234
NICE: National Institute for Health and Clinical Excellence. Donepezil, rivastigmine, galantamine and memantine for the treatment of Alzheimer’s disease (amended); September 2007. Available at: http://www.nice.org. uk/guidance/index.jsp? action=download≗36556
Masse I, Border R, Deplanque D, Al Khedr A, Richard F, Libersa C, Pasquier F. Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease. J Neurol Neurosurg Psyquiatry 2005;76:1624–1629
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Soto, M.E., Andrieu, S., Arbus, C. et al. Rapid cognitive decline in Alzheimer’s disease. Consensus paper. J Nutr Health Aging 12, 703–713 (2008). https://doi.org/10.1007/BF03028618
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DOI: https://doi.org/10.1007/BF03028618