MCI Conversion to Dementia: Clinic and Community-Based Studies

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MCI Conversion to Dementia: Clinic and Community-Based Studies Ranjan Duara, M.D. Wien Center for Alzheimer’s Disease & Memory Disorders, Miami Beach

Collaborators Wien Center, Mount Sinai, Miami Beach Ranjan Duara, MD, David Loewenstein, PhD Amarilis Acevedo, PhD, Warren Barker, MS Debbie Hurwitz, MSW, Marina Bravo, MSW Mercy Luis, MSW, Cheryl Luis, PhD Roskamp Institute, USF, Tampa Michael Mullan, MD, PhD, Fiona Crawford, PhD University of Toronto Peter St. George-Hyslop, MD

MCI to Dementia Conversion Demographics of Clinic Sample MCI With Followup (n) 210 Age of Onset (yrs) 72  9 MMSE 25  3 Diagnosis (% AD) 59% Followup Interval (yrs) 1.9  1.8 Followup Rate (%) 25.5%

MCI Study: Non-AD Diagnoses Diagnosis Number / % Vascular Cognitive Impairment 32 / 37% Psychiatric Disorders (depression, etc) 11 / 13% Other Degenerative (FTD, Parkinsons, etc) 8 / 9% Other Neurological (seizure, hydrocephalus, etc.) 35 / 41%

Criteria for MCI History of cognitive impairment (subjective, collateral, or both) Objective cognitive deficits on memory  other cognitive domains Lacking DSM III criteria for dementia Preserved functional capacity

Criteria for MCI (AD) Meets criteria for MCI Meeting NINCDS-ADRDA criteria for AD, but lacking DSM III criteria for dementia

Criteria for Conversion of MCI to Dementia in Clinic Sample Worsening of cognitive function by collateral report Worsening of objective cognitive deficits Meets DSM III criteria for dementia

APOE e4 Allele Frequency in Clinic Samples Diagnosis e4 Frequency (%) Probable AD (n=678) 29% MCI – AD (n=195) 26% MCI – Other (n=138) 14%

Conversion to Dementia Effect of AD Diagnosis 2=6.8 (p=.009)

MCI to Dementia Conversion Rates in Clinic Sample 1-yr Rate 2-yr Rate 3-yr Rate ALL MCI (n=210) 17% 31% 47% MCI - AD (n=124) 23% 41% 58% MCI - Non-AD (n=86) 11% 21% 34% 2=6.8 (p=.009) for survival curve difference of AD vs non-AD

Conversion to Dementia Effect of APOE

Conversion to Dementia Effect of Age 2=0.4 (p=.83)

Factors Influencing Follow-Up Rate in MCI Patients Predictor Data P-value Gender 26% (m) 23%(f) n.s. AD Diagnosis 32%(MCI-AD) 20% (MCI-non-AD) .006 Age at Onset of MCI 24% (60s) 29% (70s) 21% (80+) .16 Initial MMSE 24.4 (followup+) 24.9 (no followup) Initial HDRS (fup+/-) 8.4 (followup+) 8.7 (followup-)

MCI to Dementia Risk Factors in Clinic Sample No Association Age of onset Use of Aricept Education Gender Increased Risk Diagnosis of AD APOE e4 (trend)

Classification of Screening Sample MMSE (0-30) 4 Trial Recall (0-12) APOE e4 Allele Frequency Normal 24 10 12% MCI <24 5-9 >4 18% Demented 4 26%

MCI to Dementia Conversion 11% 15% 20%