Katie Palmer - Epi2008

Mild Cognitive Impairment in theGeneral Population:Occurrence and progression toAlzheimer’s diseaseKatie Palmer, Marie Curie Fellow- EUAging Research CenterDepartment of Neurobiology, Care Sciences and Society

Gradual and progressive decline inAlzheimer’s diseaseNormal cognitive agingClinicaldiagnosisCognitivefunctioningPathological changes?Symptoms?Signs?SevereADKatie PalmerSeptember 2008, Brazil2

Mild Cognitive Impairment (MCI)Not normal, not demented(Does not meet criteria (DSM IV, ICD 10) for a dementiasyndrome)Cognitive decline-Self and/or informant report-Objective cognitive testingPreserved basic activities of daily living / minimal impairment incomplex instrumental functionsPetersen et al, J Internal Medicine 2004Winblad et al, J Internal Medicine 2004Katie PalmerSeptember 2008, Brazil3

BackgroundMCI criteria have been continually revised over the past ten yearsThe latest criteria propose different MCI subtypes depending on whichcognitive domain is impairedKatie PalmerSeptember 2008, Brazil4

Background It is widely assumed that the MCI-amnestic is themost common subtype, and that MCI-amnestic oftenrepresents a preclinical phase of Alzheimer’s disease Little data is available at the population levelconcerning the prevalence of MCI subtypes It has been suggested that different MCI subtypeshave different etiologies, but data from the generalpopulation is limited concerning the predictive valueof the MCI subtypes for identifying early prodromaldementiaKatie PalmerSeptember 2008, Brazil5

Aims1) To detect the occurrence of three MCI subtypes inthe general population2) To identify cases of cognitive impairment which arenot detected by current operational criteria for MCI3) To determine the predictive value of the subtypes foridentifying future Alzheimer’s diseaseKatie PalmerSeptember 2008, Brazil6

The Kungsholmen Project,Stockholm, SwedenThe Kungsholmen Project1810 participants at baseline75+ years oldLiving in KunsgholmenBaselineFour follow-ups1st2nd3rd4th1987-1989 1991-1993 1994-1996 1997-19981999-2000Katie Palmer, Aging Research Center October 15th, IPA Osaka 7

Method1435 non-demented persons aged 75+ yearsStandard MCI criteria Subjective complaints of memory problemsObjective domain-specific cognitive deficits:Episodic memory, Visuospatial functioning, Verbal fluencyNormal general cognitive functioning (MMSE >1SD withinage/education norms)Modified MCI criteriaAs above with one exception: Definition includes any level of generalcognitive functioning (any score on the MMSE)Other cognitive impairmentNormal episodic memory, visuospatial functioning &verbal fluencyImpairment only evident in general cognitive functioning (MMSE)Katie PalmerSeptember 2008, Brazil8

Occurrence of MCI subtypesPrevalence per 100 non-demented personsMCI-Amnestic3.41.8Modified MCIcriteriaOriginal MCIcriteriaMCI-Singlenonmemory8.27.2MCI-Multidomain5.22.10 2 4 6 8 10 12Palmer et al, Am J Geri Psychiatr 2008Katie Palmer September 2008, Brazil 9

Occurrence of other cognitive impairmentMCI-AmnesticMCI-SinglenonmemoryMCI-MultidomainCognitiveImpairment-No MCI0 2 4 6 8 10 127% of thepopulation hadimpairment onthe globalcognitive task(MMSE) butperformed atnormal levels onall other domainspecifictasks.Palmer et al, Am J Geri Psychiatr 2008Katie Palmer September 2008, Brazil 10

Three year progression from MCI to ADNo impairmentOther cognitive ImpairmentSingle MCIAmnestic MCIMulti MCI0% 25% 50% 75% 100%Status at 3 year follow-upAlive no dementia Died ADPalmer et al, Am J Geri Psychiatr 2008Katie Palmer September 2008, Brazil 11

Three year progression from MCI to ADModified vs standard MCI criteriaMCI-Amnestic MCI-MultidomainsModifiedcriteriaStandardcriteriaModifiedcriteriaStandardcriteriaHazard Ratios for progression from MCI to AD, adjusted for age, sex, educationPalmer et al, Am J Geri Psychiatr 2008Katie Palmer September 2008, Brazil 12

Conclusions MCI-single non-memory domain impaired is the mostcommon MCI subtype but is not associated withimpending AD Occurrence of MCI subtypes increases whenmodified criteria are applied Positive predictive values for AD increase whenmodified criteria are used for MCI-amnestic Two-thirds of MCI-multidomains, but only one third toone half of MCI-amnestic progress to AD The standard MCI criteria fail to detect those peoplewith global cognitive deficits who have a high risk ofprogressing to ADKatie PalmerSeptember 2008, Brazil13

Laura FratiglioniLars BäckmanBengt WinbladAging Research CenterDepartment of Neurobiology, Care Sciences & Society, KIand Stockholm Gerontology Research CenterKatie PalmerAging Research Center, Karolinska Institutet, Sweden, andItalian National Research Council (CNR),Foundation Santa Lucia, Rome, ItalyFunding acknowledgementsMarie Curie Intra-European Individual Fellowship (EU)Swedish Council for Working Life and Social Research (FAS)Gamla Tjänarinnor FoundationLoo and Hans Osterman Foundation