A Conceptual Framework for Research on Subjective Cognitive Decline in Preclinical Alzheimer's Disease

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

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References

Glodzik-Sobanska L, Reisberg B, De Santi S, Babb J, Pirraglia E, Rich K . Subjective memory complaints: presence, severity and future outcome in normal older subjects. Dement Geriatr Cogn Disord. 2007; 24(3):177-84. DOI: 10.1159/000105604. View

Chary E, Amieva H, Peres K, Orgogozo J, Dartigues J, Jacqmin-Gadda H . Short- versus long-term prediction of dementia among subjects with low and high educational levels. Alzheimers Dement. 2012; 9(5):562-71. DOI: 10.1016/j.jalz.2012.05.2188. View

Perrotin A, Mormino E, Madison C, Hayenga A, Jagust W . Subjective cognition and amyloid deposition imaging: a Pittsburgh Compound B positron emission tomography study in normal elderly individuals. Arch Neurol. 2012; 69(2):223-9. PMC: 4004919. DOI: 10.1001/archneurol.2011.666. View

Tierney M, Szalai J, SNOW W, Fisher R . The prediction of Alzheimer disease. The role of patient and informant perceptions of cognitive deficits. Arch Neurol. 1996; 53(5):423-7. DOI: 10.1001/archneur.1996.00550050053023. View

Jessen F, Feyen L, Freymann K, Tepest R, Maier W, Heun R . Volume reduction of the entorhinal cortex in subjective memory impairment. Neurobiol Aging. 2005; 27(12):1751-6. DOI: 10.1016/j.neurobiolaging.2005.10.010. View

Acosta-Baena N, Sepulveda-Falla D, Lopera-Gomez C, Jaramillo-Elorza M, Moreno S, Aguirre-Acevedo D . Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011; 10(3):213-20. DOI: 10.1016/S1474-4422(10)70323-9. View

Dik M, Jonker C, Comijs H, Bouter L, Twisk J, Van Kamp G . Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly. Neurology. 2002; 57(12):2217-22. DOI: 10.1212/wnl.57.12.2217. View

Vellas B, Aisen P, Sampaio C, Carrillo M, Scheltens P, Scherrer B . Prevention trials in Alzheimer's disease: an EU-US task force report. Prog Neurobiol. 2011; 95(4):594-600. DOI: 10.1016/j.pneurobio.2011.08.014. View

Tepest R, Wang L, Csernansky J, Neubert P, Heun R, Scheef L . Hippocampal surface analysis in subjective memory impairment, mild cognitive impairment and Alzheimer's dementia. Dement Geriatr Cogn Disord. 2008; 26(4):323-9. DOI: 10.1159/000161057. View

10.

Erk S, Spottke A, Meisen A, Wagner M, Walter H, Jessen F . Evidence of neuronal compensation during episodic memory in subjective memory impairment. Arch Gen Psychiatry. 2011; 68(8):845-52. DOI: 10.1001/archgenpsychiatry.2011.80. View

11.

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

12.

Jessen F, Wiese B, Bachmann C, Eifflaender-Gorfer S, Haller F, Kolsch H . Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment. Arch Gen Psychiatry. 2010; 67(4):414-22. DOI: 10.1001/archgenpsychiatry.2010.30. View

13.

Visser P, Verhey F, Knol D, Scheltens P, Wahlund L, Freund-Levi Y . Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009; 8(7):619-27. DOI: 10.1016/S1474-4422(09)70139-5. View

14.

Scheef L, Spottke A, Daerr M, Joe A, Striepens N, Kolsch H . Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment. Neurology. 2012; 79(13):1332-9. DOI: 10.1212/WNL.0b013e31826c1a8d. View

15.

Wang P, Saykin A, Flashman L, Wishart H, Rabin L, Santulli R . Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints. Neurobiol Aging. 2005; 27(11):1613-7. PMC: 3482483. DOI: 10.1016/j.neurobiolaging.2005.09.035. View

16.

Dux M, Woodard J, Calamari J, Messina M, Arora S, Chik H . The moderating role of negative affect on objective verbal memory performance and subjective memory complaints in healthy older adults. J Int Neuropsychol Soc. 2008; 14(2):327-36. DOI: 10.1017/S1355617708080363. View

17.

Eckerstrom M, Skoogh J, Rolstad S, Gothlin M, Steineck G, Johansson B . Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q)--a research tool discriminating between subjectively cognitively impaired patients and healthy controls. Int Psychogeriatr. 2012; 25(3):420-30. DOI: 10.1017/S1041610212001846. View

18.

Reisberg B, Prichep L, Mosconi L, Roy John E, Glodzik-Sobanska L, Boksay I . The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer's disease. Alzheimers Dement. 2008; 4(1 Suppl 1):S98-S108. DOI: 10.1016/j.jalz.2007.11.017. View

19.

Rami L, Fortea J, Bosch B, Sole-Padulles C, Llado A, Iranzo A . Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients. J Alzheimers Dis. 2010; 23(2):319-26. DOI: 10.3233/JAD-2010-101422. View

20.

Petersen R . Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3):183-94. DOI: 10.1111/j.1365-2796.2004.01388.x. View