Mild Physical Impairment Predicts Alzheimer's Dementia
All participants were older adults involved in studies of cognitive and functional aging at the Knight Alzheimer's Disease Research Center (ADRC) at Washington University between January 1998 and August 2007. The ADRC recruits older adult volunteers from the greater metropolitan St. Louis area (population: 2.5 million) who are cognitively healthy or have dementia. All participants of the study were enrolled in the ADRC longitudinal study and completed annual clinical assessments. To be included in this study, individuals had to be cognitively normal at the initial clinical assessment, aged 60 and older, ambulatory, able to complete all assessments and at least one follow-up assessment, and have a Physical Performance Test (PPT) score >5 (range of possible PPT scores, from worst to best performance, is 0–36). Five hundred ten individuals completed all assessments required for this study, and 440 met the initial inclusion criteria. During follow-up, five participants were diagnosed with non-DAT dementia: two with dementia with Lewy bodies, two with vascular dementia, and one with dementia due to Parkinson's disease. These individuals were excluded from analyses, giving a final sample size of 435.
Clinical and Cognitive Assessments The clinical evaluation at baseline and at each annual follow-up visit included obtaining past medical, social, and family history from a reliable informant, usually a spouse or adult child. A clinician obtained information regarding possible cognitive change and functional loss from semistructured interviews with the informant and separately with the participant. Included in the clinical assessment protocol were the Mini-Mental State Examination, the Short Blessed Test, an aphasia battery, a medication inventory, a detailed neurological examination, and a depressive features battery.
Using all information from the clinical assessment protocol but without reference to the participant's psychometric performance, the clinician determined the Clinical Dementia Rating (CDR) for the participant. In this study, cognitive normality was denoted as a CDR of 0 and cognitive impairment as a CDR score greater than 0, where CDR 0.5, 1, 2, and 3 indicate very mild, mild, moderate, and severe dementia, respectively. The diagnosis of DAT was made in accordance with standard criteria and, in our ADRC, is confirmed by histopathology in 93% of cases, even for individuals diagnosed in the CDR 0.5 stage.
Physical Assessment After the general physical and neurological examination was completed, a trained research nurse administered the PPT. A modification of the original PPT instrument, which uses the chair rise and progressive Romberg test of standing balance to simulate stair climbing tasks, was used. Performance on these two tasks, which have been included in other physical performance batteries, has been associated with self-reported disability, nursing home placement, and mortality. Specific tasks in the modified PPT are writing a sentence, simulated eating (spooning beans into a container), lifting a book, simulated dressing (putting on and taking off a jacket), picking up a penny from the floor, turning in a complete circle, walking 50 feet, chair rise (sitting in and rising from a chair five times), and the progressive Romberg test of standing balance (standing with feet in tandem, semitandem, and side-by-side positions). The tasks on the PPT were scored on a 5-point scale, from worst to best performance (0, 1, 2, 3, 4). Total PPT score, a simple summation of the individual item scores, is a composite measure of physical function. The maximum (best) total score was 36, with lower scores indicating greater disability. Based on prior work, participants were classified as functional (PPT score ≥28) or impaired function (PPT score < 28).
Analyses were performed using SAS (SAS Institute, Inc., Cary, NC). Change from cognitively normal status to a diagnosis of DAT was the primary outcome measure. Survival analyses were used to examine whether scores on the PPT predicted time to receipt of a DAT diagnosis. Kaplan-Meier survival curves were used to test unadjusted associations between DAT diagnosis and PPT scores in the functional and impaired function ranges. Because they are able to accommodate continuous predictor variables, Cox proportional hazards models were used to examine unadjusted associations between PPT total score and time to DAT; as well as the association between time to DAT and baseline PPT total scores and testing at the functional level on the PPT while adjusting for and simultaneously testing the effects of age, sex, education, and presence of one or more apolipoprotein (APOE) ε4 alleles. P value of .05 was taken to indicate statistical significance in all analyses.
Methods
Participants
All participants were older adults involved in studies of cognitive and functional aging at the Knight Alzheimer's Disease Research Center (ADRC) at Washington University between January 1998 and August 2007. The ADRC recruits older adult volunteers from the greater metropolitan St. Louis area (population: 2.5 million) who are cognitively healthy or have dementia. All participants of the study were enrolled in the ADRC longitudinal study and completed annual clinical assessments. To be included in this study, individuals had to be cognitively normal at the initial clinical assessment, aged 60 and older, ambulatory, able to complete all assessments and at least one follow-up assessment, and have a Physical Performance Test (PPT) score >5 (range of possible PPT scores, from worst to best performance, is 0–36). Five hundred ten individuals completed all assessments required for this study, and 440 met the initial inclusion criteria. During follow-up, five participants were diagnosed with non-DAT dementia: two with dementia with Lewy bodies, two with vascular dementia, and one with dementia due to Parkinson's disease. These individuals were excluded from analyses, giving a final sample size of 435.
Clinical and Cognitive Assessments The clinical evaluation at baseline and at each annual follow-up visit included obtaining past medical, social, and family history from a reliable informant, usually a spouse or adult child. A clinician obtained information regarding possible cognitive change and functional loss from semistructured interviews with the informant and separately with the participant. Included in the clinical assessment protocol were the Mini-Mental State Examination, the Short Blessed Test, an aphasia battery, a medication inventory, a detailed neurological examination, and a depressive features battery.
Using all information from the clinical assessment protocol but without reference to the participant's psychometric performance, the clinician determined the Clinical Dementia Rating (CDR) for the participant. In this study, cognitive normality was denoted as a CDR of 0 and cognitive impairment as a CDR score greater than 0, where CDR 0.5, 1, 2, and 3 indicate very mild, mild, moderate, and severe dementia, respectively. The diagnosis of DAT was made in accordance with standard criteria and, in our ADRC, is confirmed by histopathology in 93% of cases, even for individuals diagnosed in the CDR 0.5 stage.
Physical Assessment After the general physical and neurological examination was completed, a trained research nurse administered the PPT. A modification of the original PPT instrument, which uses the chair rise and progressive Romberg test of standing balance to simulate stair climbing tasks, was used. Performance on these two tasks, which have been included in other physical performance batteries, has been associated with self-reported disability, nursing home placement, and mortality. Specific tasks in the modified PPT are writing a sentence, simulated eating (spooning beans into a container), lifting a book, simulated dressing (putting on and taking off a jacket), picking up a penny from the floor, turning in a complete circle, walking 50 feet, chair rise (sitting in and rising from a chair five times), and the progressive Romberg test of standing balance (standing with feet in tandem, semitandem, and side-by-side positions). The tasks on the PPT were scored on a 5-point scale, from worst to best performance (0, 1, 2, 3, 4). Total PPT score, a simple summation of the individual item scores, is a composite measure of physical function. The maximum (best) total score was 36, with lower scores indicating greater disability. Based on prior work, participants were classified as functional (PPT score ≥28) or impaired function (PPT score < 28).
Statistical Analyses
Analyses were performed using SAS (SAS Institute, Inc., Cary, NC). Change from cognitively normal status to a diagnosis of DAT was the primary outcome measure. Survival analyses were used to examine whether scores on the PPT predicted time to receipt of a DAT diagnosis. Kaplan-Meier survival curves were used to test unadjusted associations between DAT diagnosis and PPT scores in the functional and impaired function ranges. Because they are able to accommodate continuous predictor variables, Cox proportional hazards models were used to examine unadjusted associations between PPT total score and time to DAT; as well as the association between time to DAT and baseline PPT total scores and testing at the functional level on the PPT while adjusting for and simultaneously testing the effects of age, sex, education, and presence of one or more apolipoprotein (APOE) ε4 alleles. P value of .05 was taken to indicate statistical significance in all analyses.
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