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Impact of Functional Deficits in Instrumental Activities of Daily Living in Mild Cognitive Impairment: A Clinical Algorithm to Predict Progression to Dementia

Devanand, Davangere P. MD; Liu, Xinhua PhD; Brown, Patrick J. PhD

Alzheimer Disease & Associated Disorders: January-March 2017 - Volume 31 - Issue 1 - p 55–61
doi: 10.1097/WAD.0000000000000160
Original Articles

Background: The utility of functional deficits in patients with mild cognitive impairment is not established.

Materials and Methods: In 3886 individuals with mild cognitive impairment evaluated and followed at 34 National Alzheimer Coordinating Center sites, informant-reported Pfeffer Functional Activities Questionnaire (FAQ) items associated with progression to dementia were derived in a training set (n=1943) and tested in the validation set (n=1943).

Results: In the training set, the optimal combination comprised 6 FAQ items (FAQ6): difficulties with finances (2 items), remembering events/appointments, playing games of skill, current events, and travel. In the validation set, hazard ratio for dementia increased from 2.00 for 1 FAQ6 deficit to 5.56 for 6 FAQ6 deficits. In patients 50 to 67 years old with high Mini Mental State Exam scores, dementia risk rose from 12.06% for no FAQ6 deficits to 56.75% for 6 functional deficits. Likelihood of progression to dementia reached 80% to 89% in older age groups with low Mini Mental State Exam and severe FAQ6 deficits.

Conclusions: Specific functional deficits increased dementia risk and, with age and global cognition, constituted a validated clinical algorithm to estimate dementia risk. Clinicians can use this clinically important algorithm to personalize decision-making about further investigation and identify high-risk patients for early treatment or inclusion in clinical trials.

Supplemental Digital Content is available in the text.

*Department of Psychiatry, Division of Geriatric Psychiatry, New York State Psychiatric Institute and Columbia University Medical Center

Division of Biostatistics in the Mailman School of Public Health, Columbia University, New York, NY

Supported by National Institute on Aging (NIA) grants U01AG016976 and 2010-JI-01 to the National Alzheimer’s Coordinating Center (NACC), NIA grant R01AG041795 (to D.P.D.), and from the National Institute of Mental Health to P.J.B. (K23MH09097). The NACC database is supported by NIA/NIH Grant U01 AG016976. The funding source, NIA, designed and conducted the NACC study and provided the database for the analyses in this report. NIA did not play a role in the analyses, interpretation, or writing of this report. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), and P50 AG005681 (PI John Morris, MD).

D.P.D.: conceptualized the study; X.L. and P.J.B. conducted the analyses; D.P.D.: drafted the paper and all authors edited the paper and approved the final version for submission. D.P.D. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

D.P.D. has received consulting fees from AbbVie, Lundbeck, Astellas, and Intracellular Therapeutics. The remaining authors declare no conflicts of interest.

Reprints: Davangere P. Devanand, MD, Department of Psychiatry and Neurology, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 126, New York, NY 10032 (e-mail:

Received February 17, 2016

Accepted June 25, 2016

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