The Prognosis in Alzheimer's Disease: 'How Far' Rather Than 'How Fast' Best Predicts the Course

Department of Neurology, University of Massachusetts Medical School, Worcester 01655.
JAMA Neurology (Impact Factor: 7.42). 09/1990; 47(8):851-6. DOI: 10.1001/archneur.1990.00530080033007
Source: PubMed


Clinical features at the initial examination of 42 patients with probable Alzheimer's disease were tested for prognostic value at subsequent follow-up of 54 +/- 25 months. These potential prognostic features were of three types: degree of severity features (eg, IQ scores); variable clinical features (eg, extrapyramidal signs); and individual distinguishing features (eg, gender, education, and age). The power of these potential prognostic features to predict prognosis was assessed using the Kaplan-Meier life-tables method and the Cox proportional hazards model. Three clinical end points were considered: total dependence in activities of daily living; incontinence; and institutionalization at follow-up. Degree of severity features (subtests of the Wechsler Adult Intelligence Scale-Revised and the Wechsler Memory Scale, and the Clinical Severity Score) predicted subsequent dependence in activities of daily living, incontinence, and institutionalization. Historical disease duration, age, gender, family history of dementia, retrospective rate of progression, anxiety, psychosis, depression, and extrapyramidal signs did not influence prognosis. These results suggest that initial degree of severity ("how far") rather than variation in the rate of progression ("how fast") best predicts prognosis in the early to intermediate stages of Alzheimer's disease. The relationship of disease severity to prognosis should be taken into account before concluding that there are subtypes of Alzheimer's disease that have different rates of progression.

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    • "Studies investigating the rate of disease progression by measuring cognitive and functional abilities over time yielded variable results. Some reports demonstrated that EOAD shows a more rapid progression [15-17], and others found that AOO is not a major predictor of the rate of progression [18,19]. "
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    ABSTRACT: Alzheimer disease (AD) is a devastating neurodegenerative disease affecting 1 in 68 in the population. An arbitrary cutoff 65 years as the age of onset to distinguish between early- and late-onset AD has been proposed and has been used in the literature for decades. As the majority of patients develop AD after 65 years of age, most clinical trials address this population. While the early-onset cases represent only 1% to 6% of AD cases, this population is the active working subset and thus contributes to a higher public health burden per individual, and early-onset cases are the most devastating at the level of the individual and their families. In this review, we compare and contrast the clinical, neuropsychological, imaging, genetic, biomarker, and pathological features of these two arbitrary groups. Finally, we discuss the ethical dilemma of non-abandonment and justice as it pertains to exclusion of the early-onset AD patients from clinical trials.
    Alzheimer's Research and Therapy 02/2011; 3(1):4. DOI:10.1186/alzrt63 · 3.98 Impact Factor
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    • "By contrast a study from the Baylor College of Medicine [27] did not find such an effect on MMSE score decline, though the sample was smaller and thus may have been under-powered. Similarly Drachman and colleagues found few significant effects on the rate of decline in AD despite studying a wide range of predictor variables in a sample of just 42 patients [28]. On the other hand Mortimer and colleagues found a significant association between psychotic symptoms and the rate of cognitive decline in a sample of 65 patients [29]; we also reported a link between psychotic symptoms and cognitive status in our patients [25]. "
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    ABSTRACT: Cognitive reserve is thought to influence the degree of neuropathology needed for diagnosis of Alzheimer disease (AD). Cognitive reserve can be operationally defined as the hypothesized capacity of the mature adult brain to sustain the effects of disease or injury without manifesting clinical symptoms of AD, but sufficient to cause clinical dementia in an individual possessing less cognitive reserve. Its effect on the subsequent course of AD is less clear. Pre-morbid IQ is a useful measure of cognitive reserve. We studied 659 consecutive patients with AD at a tertiary referral memory clinic. Patients were assessed on six cognitive tests at baseline. Activities of Daily Living (ADL) were measured on the Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). The National Adult Reading Test (NART) was used to estimate pre-morbid IQ. Patients were followed up after starting a cholinesterase inhibitor over 78 weeks. Mixed general linear models estimated the effects of NART on cognition and ADL. Three hundred and fifty-five patients had NART scored with a mean estimated pre-morbid IQ of 104.7 (standard deviation 18.5). NART increased overall cognitive ability by 2.7% for every 10 IQ points (p < .001). There was a trend for an effect on the change in cognition over time (p = .065) with higher NART associated with improvement of cognitive ability over time. After adjusting for age and sex, a 10 point increase in NART was associated with an improvement of 2% in ADL scores, but this effect was explained by NART's influence on contemporaneous cognitive ability. Our data support the hypothesis that cognitive reserve continues to have a limited influence on cognition after AD has been diagnosed and thus, indirectly, has an impact on ADL.
    BMC Psychiatry 04/2008; 8(1):27. DOI:10.1186/1471-244X-8-27 · 2.21 Impact Factor
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    • "Among patients with VaD, changes in executive functioning and memory over a one-year period were predictive of IADL and BADL changes, respectively, suggesting that different cognitive functions subserve complex and rote, habituated functional activities. These findings are consistent with prior cross-sectional studies in AD linking executive functioning to IADLs (Boyle et al., 2003; Cahn-Weiner et al., 2003) and memory to BADLs (Drachman et al., 1990) and augment the cognitive-functional literature by demonstrating that such relationships maintained in VaD. "
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    ABSTRACT: This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year. Twenty-four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant-based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow-up assessment was conducted one-year post-baseline. Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively. Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes.
    International Journal of Geriatric Psychiatry 08/2006; 21(8):752-4. DOI:10.1002/gps.1556 · 2.87 Impact Factor
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