GAIT ABNORMALITY AND NON-ALZHEIMER’S DEMENTIA ABNORMALITY OF GAIT AS A PREDICTOR OF NON-ALZHEIMER’S DEMENTIA JOE VERGHESE, M.D., RICHARD B. LIPTON, M.D., CHARLES B. HALL, PH.D., GAIL KUSLANSKY, PH.D., MINDY J. KATZ, M.P.H., AND HERMAN BUSCHKE, M.D. ABSTRACT syndromes account for 30 to 50 percent of cases in Background Neurologic abnormalities affecting elderly patients who present for evaluation of abnor- gait occur early in several types of non-Alzheimer’s de- mal gait.2-5 Like the frequency of gait disorders, the mentias, but their value in predicting the development prevalence of dementia also increases with age.6 Al- of dementia is uncertain. though Alzheimer’s disease is the most common type Methods We analyzed the relation between neuro- of dementia, vascular and other non-Alzheimer’s de- logic gait status at base line and the development of mentias account for 30 to 50 percent of all cases of de- dementia in a prospective study involving 422 sub- mentia.6-9 The prevalence of vascular dementia is high jects older than 75 years of age who lived in the com- worldwide and is particularly high in Asia.6,9 Patients munity and did not have dementia at base line. Cox with vascular dementia may be more depressed, have proportional-hazards regression analysis was used to calculate hazard ratios with adjustment for potential greater functional impairment, and require different confounding demographic, medical, and cognitive diagnostic and therapeutic approaches than patients variables. with Alzheimer’s disease.10 Recent studies have fo- Results At enrollment, 85 subjects had neurologic cused on identifying persons who are at high risk for gait abnormalities of the following types: unsteady gait Alzheimer’s disease, often with the use of cognitive (in 31 subjects), frontal gait (in 12 subjects), hemipa- tests.11,12 Predictors of non-Alzheimer’s dementia have retic gait (in 11 subjects), neuropathic gait (in 11 sub- been less well characterized.13,14 jects), ataxic gait (in 10 subjects), parkinsonian gait (in According to current criteria, the early appearance 8 subjects), and spastic gait (in 2 subjects). During fol- of abnormalities of gait makes a diagnosis of probable low-up (median duration, 6.6 years), there were 125 Alzheimer’s disease unlikely.15,16 In contrast, gait dis- newly diagnosed cases of dementia, 70 of them cases orders are a well-known presenting feature of non-Alz- of Alzheimer’s disease and 55 cases of non-Alzheimer’s dementia (47 of which involved vascular dementia and heimer’s dementias such as vascular and parkinsonian 17-21 8 of which involved other types of dementia). Subjects dementias. Because gait abnormalities are often with neurologic gait abnormalities had a greater risk present at the onset of non-Alzheimer’s dementia, we of development of dementia (hazard ratio, 1.96 [95 per- hypothesized that they may precede and predict di- cent confidence interval, 1.30 to 2.96]). These subjects agnosis. had an increased risk of non-Alzheimer’s dementia For 21 years, the Bronx Aging Study has conducted (hazard ratio, 3.51 [95 percent confidence interval, 1.98 detailed clinical evaluations of a community-based co- to 6.24]), but not of Alzheimer’s dementia (hazard ra- hort of subjects who did not have dementia at base tio, 1.07 [95 percent confidence interval, 0.57 to 2.02]). line,22,23 providing an opportunity to identify risk fac- Of non-Alzheimer’s dementias, abnormal gait predict- tors for non-Alzheimer’s dementia. We examined the ed the development of vascular dementia (hazard ra- tio, 3.46 [95 percent confidence interval, 1.86 to 6.42]). role of abnormal gait in predicting not only the risk of Among the types of abnormal gait, unsteady gait pre- dementia, but also the risk of Alzheimer’s disease as dicted vascular dementia (hazard ratio, 2.61), as did compared with non-Alzheimer’s dementia. frontal gait (hazard ratio, 4.32) and hemiparetic gait (hazard ratio, 13.13). METHODS Conclusions The presence of neurologic gait ab- Study Population normalities in elderly persons without dementia at base line is a significant predictor of the risk of devel- Study design and recruitment methods for the Bronx Aging opment of dementia, especially non-Alzheimer’s de- Study have been described previously. 22,23 Briefly, we enrolled Eng- mentia. (N Engl J Med 2002;347:1761-8.) lish-speaking subjects between 75 and 85 years of age. Criteria for exclusion included a previous diagnosis of idiopathic Parkinson’s dis- Copyright © 2002 Massachusetts Medical Society. ease, liver disease, alcoholism, or known terminal illness; visual or hearing impairment that interfered with completion of neuropsy- chological tests; and presence of dementia. The inception cohort AIT disorders become increasingly com- mon with advancing age, occurring in 8 to 19 percent of elderly persons residing in the From the Department of Neurology (J.V., R.B.L., C.B.H., G.K., M.J.K., H.B.) and the Department of Epidemiology and Social Medicine (R.B.L., 1,2 community. Common causes of abnormal C.B.H.), Albert Einstein College of Medicine, Bronx, N.Y.; and Innovative Ggait in elderly persons include neurologic diseases, ar- Medical Research and the Center for Healthier Aging (Advanced PCS), Hunt Valley, Md. (R.B.L.). Address reprint requests to Dr. Verghese at the thritis, and acquired foot deformities. Neurologic dis- Einstein Aging Study, Albert Einstein College of Medicine, 1165 Morris Park eases such as neuropathies, stroke, and parkinsonian Ave., Bronx, NY 10461, or at [email protected]. N Engl J Med, Vol. 347, No. 22 · November 28, 2002 · www.nejm.org · 1761 The New England Journal of Medicine was middle-class, mostly white (90 percent), and largely female Neuropsychological Evaluation (64.5 percent). Subjects were screened to rule out dementia and were included if they made 8 or fewer errors on the Blessed Infor- A battery of neuropsychological tests was administered at study mation–Memory–Concentration test (worst possible score, 32 er- visits in order to assess the following cognitive domains: general cog- nitive status, assessed by the Blessed Information–Memory–Con- rors).24 This test has high test–retest reliability (0.86) and correlates centration test24 and the verbal and performance IQ according to well with the pathology of Alzheimer’s disease.25,26 Subjects were the Wechsler Adult Intelligence Scale30; attention, assessed by the interviewed about their medical history with the use of structured 30 questionnaires. Functional status was assessed with the subscale for Digit Span subtest of the Wechsler Adult Intelligence Scale ; ex- 24 ecutive function, assessed by the Digit–Symbol Substitution sub- activities of daily living from the Blessed Dementia Scale. When- 30 ever possible, a close friend or family member was also interviewed test of the Wechsler Adult Intelligence Scale ; memory, assessed by the Fuld Object-Memory Evaluation31 and the five-item Blessed by a study clinician in order to confirm the history and assess func- 30 tional status. Written informed consent was obtained at enrollment, memory phrase subtest (the selective reminding test, an exten- and subjects were asked to consider eventual participation in an au- sively validated memory test, was not administered at the first visit, and results on this test are not reported here); visual–perceptual topsy program. The local institutional review board approved the 32 study protocol. processing, assessed by Raven’s Progressive Matrices, Set A, and by the Object-Assembly subtest of the Wechsler Adult Intelligence A total of 488 subjects were enrolled between 1980 and 1983, 30 33 and the study period ended in 2001. In 1992, the Bronx Aging Scale ; motor skills, assessed by the Purdue Pegboard test ; lan- guage skills, assessed by the Category Fluency Test 34; and mood, Study was incorporated into the Einstein Aging Study. Subjects had 35 follow-up visits every 12 to 18 months, at which they underwent assessed by the self-rating Zung depression scale. detailed neurologic and neuropsychological evaluations. We exclud- ed 65 subjects who did not have a follow-up visit, either because Diagnosis of Dementia they died, because they moved, or because they declined to re- Subjects in whom dementia was suspected on the basis of clinical 22,23 turn. We excluded one subject both of whose legs had been am- and neuropsychological evaluations, worsening scores on the Blessed putated above the knee. After these exclusions, 422 subjects (86.5 Information–Memory–Concentration test, or the observations of percent) remained eligible for the study. Although 79 subjects sub- study investigators underwent a workup.22,23 The presence or ab- sequently dropped out of the study, the mean (±SD) follow-up was sence of gait impairment was not used to trigger evaluation. The similar among the 8 subjects with abnormal gait who dropped out workup included computed tomographic scanning and blood tests and the 71 without abnormal gait who dropped out (6.6±4.2 years (complete blood count, routine chemical screen, liver-function and vs. 7.2±5 years, P=0.70). thyroid-function tests, measurement of vitamin B12 and folate levels, and serologic testing for syphilis) and did not vary with gait status. Assessment of Gait Diagnoses of dementia were assigned according to the criteria of Neurologic abnormalities affecting gait were diagnosed after clin- the Diagnostic and Statistical Manual of Mental Disorders, third edi- ical examination by board-certified neurologists.2,3,27 Gait impair- tion (DSM-III),36 at case conferences attended by at least one study ments due solely to nonneurologic causes such as arthritis were not neurologist, a neuropsychologist, and a geriatric nurse or social classified as abnormal gait.