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March 12, 1997, Vol 277, No. 10 >
ARTICLE | March 12, 1997

Predicting Time to Nursing Home Care and Death in Individuals With Alzheimer Disease FREE

Yaakov Stern, PhD; Min-Xing Tang, PhD; Marilyn S. Albert, PhD; Jason Brandt, PhD; Diane M. Jacobs, PhD; Karen Bell, MD; Karen Marder, MD; Mary Sano, PhD; Devangere Devanand, MD; Steven M. Albert, PhD; Frederick Bylsma, PhD; Wei-Yann Tsai, PhD
[+] Author Affiliations

Reprints: Yaakov Stern, PhD, Sergievsky Center, 630 W 168th St, New York, NY 10032.


JAMA. 1997;277(10):806-812. doi:10.1001/jama.1997.03540340040030
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Article
References

Objective.  —To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies.

Design.  —Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed.

Setting.  —Three AD research centers.

Patients.  —All patients met National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit.

Intervention.  —Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features.

Main Outcome Measures.  —(1) Requiring the equivalent of nursing home placement and (2) death.

Results.  —Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted.Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients.When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients.

Conclusions.  —The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

REFERENCES

1 +
Stern Y, Brandt J, Albert M, et al.  Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission and death in Alzheimer's disease . Neurology . 1994;;44:2300-2307.
2 +
Jacobs D, Sano M, Marder K, et al.  Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline . Neurology . 1994;;44:1215-1220.
3 +
Stern Y, Mayeux R, Sano M, et al.  Predictors of disease course in patients with probable Alzheimer's disease . Neurology . 1987;;37:1649-1653.
4 +
Chui HC, Lyness S, Sobel E, et al.  Prognostic implications of symptomatic behaviors in Alzheimer's disease . In: Heterogeneity of Alzheimer's Disease . New York, NY: Springer-Verlag; 1992;:12-24.
5 +
Mortimer JA, Ebbitt B, Jun SP, Finch MD.  Predictors of cognitive and functional decline in patients with probable Alzheimer's disease . Neurology . 1992;;42:1689-1696.
6 +
Stern Y, Mayeux R, Sano M, Chen J.  Prognostic factors for the progression of probable Alzheimer's disease . Bull Clin Neurosci . 1989;;54:73-79.
7 +
Stern Y, Folstein M, Albert M, et al.  Multicenter study of predictors of disease course in Alzheimer disease (the 'Predictors Study'), I . Alzheimer Dis Assoc Disord . 1993;;7:3-21.
8 +
McKhann G, Drachman D, Folstein M, et al.  Clinical diagnosis of Alzheimer's disease . Neurology . 1984;;34:939-944.
9 +
Mayeux R, Stern Y, Sano M, et al.  Clinical and biochemical correlates of bradyphrenia in Parkinson's disease . Neurology . 1987;;37:1130-1134.
10 +
Correction: Neurology . 1987;;37:1693.
11 +
Sano M, Stern Y, Mayeux R, et al.  A standardized technique for establishing the onset symptoms of probable Alzheimer's disease . J Clin Exp Neuropsychol . 1987;;9:65.
12 +
Stern MB, Hurting HI.  The clinical characteristics of Parkinson's disease and Parkinsonian syndromes: diagnosis and assessment . In: The Comprehensive Management of Parkinson's Disease . New York, NY: PMA Corp; 1978;:3-50.
13 +
Richards M, Marder K, Bell K, et al.  Interrater reliability of extrapyramidal signs in a group assessed for dementia . Arch Neurol . 1991;;48:1147-1149.
14 +
Devanand DP, Miller L, Richards M, et al.  The Columbia University scale for psychopathology in Alzheimer's disease . Arch Neurol . 1992;;49:371-376.
15 +
Mayeux R, Stern Y, Rosen J, Leventhal J.  Depression, intellectual impairment and Parkinson's disease . Neurology . 1981;;31:645-650.
16 +
Stern Y, Sano M, Paulson J, Mayeux R.  Modified Mini-Mental State Examination: validity and reliability . Neurology . 1987;;37( (suppl 1) ):179.
17 +
Folstein MF, Folstein SE, McHugh PR.  'Mini-Mental State': a practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975;;12:189-198.
18 +
Wechsler D. Wechsler Adult Intelligence Scale— Revised . New York, NY: Psychological Corp; 1981;.
19 +
Blessed G, Tomlinson BE, Roth M.  The association between quantitative measures of senile change in the cerebral grey matter of elderly subjects . Br J Psychol . 1968;;114:797-811.
20 +
Hughes CP, Berg L, Danziger WL, et al.  A new clinical scale for the staging of dementia . Br J Psychiatry . 1982;;146:566-572.
21 +
Stern Y, Albert SM, Sano M, et al.  Assessing patient dependence in Alzheimer's disease . J Gerontol . 1994;;49:M216-M222.
22 +
Katzman R, Brown T, Fuld P, et al.  Validation of a short orientation-memory-concentration test of cognitive impairment . Am J Psychiatry . 1983;; 140:734-739.
23 +
Buschke H, Fuld PA.  Evaluating storage, retention, and retrieval in disordered memory and learning . Neurology . 1974;;24:1019-1025.
24 +
Hixson J, Vernier D.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhAI . J Lipid Res . 1991;;31:545-548.
25 +
Collet D. Modelling Survival Data in Medical Research . London, England: Chapman and Hall; 1994;:153.
26 +
Tysnes OB, Vollset SE, Larsen JP, Aarli JA.  Prognostic factors and survival in amyotrophic lateral sclerosis . Neuroepidemiology . 1994;;13:226-235.
27 +
Corder EH, Saunders AM, Strittmatter WJ, et al.  Apolipoprotein E, survival in Alzheimer's disease patients, and competing risks of death and Alzheimer's disease . Neurology . 1995;;45:1323-1328.
28 +
Frisoni GB, Govoni S, Geroldi C, et al.  Gene dose of the є4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer's disease . Ann Neurol . 1995;;37:596-604.
29 +
van Dujin CM, de Knijff P, Wehnert A, et al.  The apolipoprotein E є2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival . Ann Neurol . 1995;;37:605-610.

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1 +
Stern Y, Brandt J, Albert M, et al.  Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission and death in Alzheimer's disease . Neurology . 1994;;44:2300-2307.
2 +
Jacobs D, Sano M, Marder K, et al.  Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline . Neurology . 1994;;44:1215-1220.
3 +
Stern Y, Mayeux R, Sano M, et al.  Predictors of disease course in patients with probable Alzheimer's disease . Neurology . 1987;;37:1649-1653.
4 +
Chui HC, Lyness S, Sobel E, et al.  Prognostic implications of symptomatic behaviors in Alzheimer's disease . In: Heterogeneity of Alzheimer's Disease . New York, NY: Springer-Verlag; 1992;:12-24.
5 +
Mortimer JA, Ebbitt B, Jun SP, Finch MD.  Predictors of cognitive and functional decline in patients with probable Alzheimer's disease . Neurology . 1992;;42:1689-1696.
6 +
Stern Y, Mayeux R, Sano M, Chen J.  Prognostic factors for the progression of probable Alzheimer's disease . Bull Clin Neurosci . 1989;;54:73-79.
7 +
Stern Y, Folstein M, Albert M, et al.  Multicenter study of predictors of disease course in Alzheimer disease (the 'Predictors Study'), I . Alzheimer Dis Assoc Disord . 1993;;7:3-21.
8 +
McKhann G, Drachman D, Folstein M, et al.  Clinical diagnosis of Alzheimer's disease . Neurology . 1984;;34:939-944.
9 +
Mayeux R, Stern Y, Sano M, et al.  Clinical and biochemical correlates of bradyphrenia in Parkinson's disease . Neurology . 1987;;37:1130-1134.
10 +
Correction: Neurology . 1987;;37:1693.
11 +
Sano M, Stern Y, Mayeux R, et al.  A standardized technique for establishing the onset symptoms of probable Alzheimer's disease . J Clin Exp Neuropsychol . 1987;;9:65.
12 +
Stern MB, Hurting HI.  The clinical characteristics of Parkinson's disease and Parkinsonian syndromes: diagnosis and assessment . In: The Comprehensive Management of Parkinson's Disease . New York, NY: PMA Corp; 1978;:3-50.
13 +
Richards M, Marder K, Bell K, et al.  Interrater reliability of extrapyramidal signs in a group assessed for dementia . Arch Neurol . 1991;;48:1147-1149.
14 +
Devanand DP, Miller L, Richards M, et al.  The Columbia University scale for psychopathology in Alzheimer's disease . Arch Neurol . 1992;;49:371-376.
15 +
Mayeux R, Stern Y, Rosen J, Leventhal J.  Depression, intellectual impairment and Parkinson's disease . Neurology . 1981;;31:645-650.
16 +
Stern Y, Sano M, Paulson J, Mayeux R.  Modified Mini-Mental State Examination: validity and reliability . Neurology . 1987;;37( (suppl 1) ):179.
17 +
Folstein MF, Folstein SE, McHugh PR.  'Mini-Mental State': a practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975;;12:189-198.
18 +
Wechsler D. Wechsler Adult Intelligence Scale— Revised . New York, NY: Psychological Corp; 1981;.
19 +
Blessed G, Tomlinson BE, Roth M.  The association between quantitative measures of senile change in the cerebral grey matter of elderly subjects . Br J Psychol . 1968;;114:797-811.
20 +
Hughes CP, Berg L, Danziger WL, et al.  A new clinical scale for the staging of dementia . Br J Psychiatry . 1982;;146:566-572.
21 +
Stern Y, Albert SM, Sano M, et al.  Assessing patient dependence in Alzheimer's disease . J Gerontol . 1994;;49:M216-M222.
22 +
Katzman R, Brown T, Fuld P, et al.  Validation of a short orientation-memory-concentration test of cognitive impairment . Am J Psychiatry . 1983;; 140:734-739.
23 +
Buschke H, Fuld PA.  Evaluating storage, retention, and retrieval in disordered memory and learning . Neurology . 1974;;24:1019-1025.
24 +
Hixson J, Vernier D.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhAI . J Lipid Res . 1991;;31:545-548.
25 +
Collet D. Modelling Survival Data in Medical Research . London, England: Chapman and Hall; 1994;:153.
26 +
Tysnes OB, Vollset SE, Larsen JP, Aarli JA.  Prognostic factors and survival in amyotrophic lateral sclerosis . Neuroepidemiology . 1994;;13:226-235.
27 +
Corder EH, Saunders AM, Strittmatter WJ, et al.  Apolipoprotein E, survival in Alzheimer's disease patients, and competing risks of death and Alzheimer's disease . Neurology . 1995;;45:1323-1328.
28 +
Frisoni GB, Govoni S, Geroldi C, et al.  Gene dose of the є4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer's disease . Ann Neurol . 1995;;37:596-604.
29 +
van Dujin CM, de Knijff P, Wehnert A, et al.  The apolipoprotein E є2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival . Ann Neurol . 1995;;37:605-610.

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