Reliable assessment of change from previous cognitive functioning is a prerequisite for determining the possible presence of neurodegenerative diseases such as Alzheimer's disease (AD). We investigated whether standardized change scores on the German version of the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB) could be used for early diagnosis of AD and whether change scores on the CERAD-NAB are superior in this respect to scores recorded on 1 occasion only. Three hundred seventy-four normal control subjects were assessed twice. Data from 95 patients with mostly mild probable AD were collected at their first entry to a memory clinic and an average of 1.1 +/- 0.24 years later. It is concluded that repeated testing with the CERAD-NAB does not generally add to improved diagnostic accuracy for mild and very mild AD and cannot, therefore, be recommended as a routine clinical procedure.
Diagnostic tests yield measurements on very different types of scales. Quantitative scales may consist of non-negative integers, either unbounded or bounded, with a fixed number of different values, or they may consist of continuous or percentage values. Remembering a different threshold value for each diagnostic variable would be cumbersome, in particular if covariates have to be taken into account. As a convenient way to overcome such problems we propose to compute z-scores for all measurements. They will be adjusted for covariates so that any individual can be judged on any test result on one single scale with an appropriate standard normal quantile as threshold. Two issues need to be addressed: Selection of covariates in the regression model which delivers the adjustment and normality of the residuals. The first will be treated by cross-validation and the latter by applying an appropriate transformation. We apply this methodology to neuropsychological tests and adjust for age, length of education and sex. Normality of residuals is needed on the diagnostically relevant side only. This allows to use parametric transformations, which can be easily implemented, e.g. in database systems. Since we have measurements at baseline and at follow-up we also analyze change values in a similar manner. For ease of interpretation, we transform the resulting z-scores back to the original scale.
The epsilon4 allele of the ApoE gene has a negative impact on cognitive performance, notably on episodic memory functions, in physically and mentally healthy aged persons. Practice effects seen in carriers of the ApoE epsilon4 were inferior in most areas tested to the effects seen in ApoE epsilon4 non-carriers. Further follow-up of these subjects will help to determine the clinical significance of these findings.
The new diagnostic criteria for mild cognitive impairment (MCI) from the International Working Group on Mild Cognitive Impairment (Winblad et al., 2004, p. 243) list "evidence of decline over time in objective cognitive tasks" as one diagnostic sign, implying the repeated neuropsychological testing. This study aimed to compare different assessment methods of longitudinal change based on the performances of 366 cognitively healthy participants (237 men, 129 women) examined with a German version of the California Verbal Learning Test (Delis, Kramer, Kaplan, & Ober, 1987) at baseline and 2 years later. Age, education, gender, and baseline performance were taken into account. Results revealed marked practice effects after 2 years. Normal ranges for change that controls for practice effects and regression to the mean proved to be superior to other reliable change indexes. This new method allows for more valid interpretation of change in neuropsychological functioning and thus diagnosis of MCI.
In addition to cognitive decline, current diagnostic criteria for Alzheimer's disease (AD) require evidence of impaired social and/or occupational functioning. The Nurses' Observation Scale for Geriatric Patients (NOSGER) is used to rate the frequency of disturbances in everyday behaviors and, although not specifically developed for this purpose, is often applied for diagnostic purposes. The NOSGER assesses six dimensions: Memory, Instrumental Activities of Daily Living (IADLs), Self-Care (ADL), Mood, Social Behavior, and Disturbing Behavior. The goals of this study were 1) to establish normative data for the NOSGER as a function of demographic variables (i.e., age, years of education, and gender) in healthy elderly subjects; 2) to obtain cutoff values distinguishing healthy elderly subjects from probable AD patients with mild dementia; and 3) to describe the natural course of behavioral changes occurring in mild AD according to the NOSGER dimensions. NOSGER data of 445 normal controls [NCs, 376 men, 69 women; Mini-Mental Status Examination (MMSE) = 28.8 +/- 1.17] and 217 probable AD patients with mild dementia (97 men, 120 women; MMSE = 26.1 +/- 1.59) from the Memory Clinic of Basel, Switzerland, were analyzed. Cutoff scores for distinguishing between average NCs and mildly demented AD patients ranged between 7 and 9 for different NOSGER dimensions. Formulae to obtain demographically adjusted and z-transformed NOSGER dimension and MMSE scores for assessment of individual cases were determined. NCs were best distinguished from patients in the NOSGER dimension Mood, followed by Memory, ADLs, Social Behavior, and Disturbing Behavior. Linear courses of behavioral deterioration were found-in four NOSGER dimensions (Memory, IADLs, Mood, and Social Behavior) in these mildly demented patients. No quadratic course was found for any of the NOSGER dimensions. The NOSGER revealed good discriminatory power in those behavioral dimensions affected in early stages of AD and is suitable for monitoring behavioral changes as a function of disease progression. Its use in combination with the MMSE for dementia screening purposes is recommended.
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