Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease

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Abstract

Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimer's disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimer's disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n = 15) and MCI subjects (n = 25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease.

Introduction

Mild cognitive impairment (MCI) is a widely cited concept in clinical research on ageing-related cognitive disorder. Generally, it refers to subclinical complaints of memory functioning in elderly people, which are considered to have a high probability of evolving towards Alzheimer's disease (AD). Cognitive impairment without dementia is so common among elderly people that it has been regarded as an inevitable feature of the ageing process. Several clinical labels have been proposed to describe this end of the normal cognitive range, such as benign senescent forgetfulness (Kral, 1962), age-associated memory impairment (Crook et al., 1986), mild cognitive decline (ICD-10, 1993), mild neurocognitive decline (DSM-IV, 1994), and mild cognitive impairment (Petersen et al., 1997, DeCarli, 2003). Benign senescent forgetfulness was one of the earliest terms to denote a stable impairment, commonly featuring depressive symptoms (Kral, 1962). On the other hand, age-associated memory impairment refers to subjective complaints of memory loss in elderly people, verified by a decrease of at least one standard deviation (SD) in a formal memory test in comparison with means established for young adults (Crook et al., 1986). This term was criticised by Levy and his colleagues, who found that age-associated memory impairment was a concept too restrictive in terms of the nature of the deficit and pointed out that cognitive impairment itself commonly occurs with other deficits. They proposed the term “ageing-associated cognitive decline” with a wider range of cognitive functions, such as attention, memory, learning, thinking, language and visuospatial function, and emphasized that it refers to an objective decline in cognitive functioning due to the physiological process of ageing (Levy, 1994). Within ICD-10, the criteria given for mild cognitive disorder refer to disorders of memory, learning and concentration (ICD-10, 1993). DSM-IV proposed a similar entity, “mild neurocognitive disorder”, which also encompasses perceptual-motor, linguistic and central executive functions besides memory and learning difficulties (DSM-IV, 1994). Petersen and his colleagues initially used the term to refer to complaints of memory loss with normal general cognitive functioning and retained ability to carry out activities of daily living (Petersen et al., 1997). Ritchie and his colleagues examined whether this type of cognitive deficit was partly due to an underlying disease which might be differentiated from normal ageing-related physiological changes. They reviewed the conceptual basis and current clinical status of mild cognitive impairment and concluded that MCI was based on a pathological model of cognitive change, it was applicable to cognitive impairment only in elderly people, and it was not generally thought to be a direct consequence of a systemic disease, rather a risk factor for senile dementia (Ritchie and Touchon, 2000). Other authors defined MCI as a prodrome of Alzheimer's disease or a clinically heterogeneous group of patients at increased risk of dementia due to any cause. Morris (2005) suggested that MCI in many cases represents a transitional state between normal cognition and AD. The most common subset of subjects with MCI are patients with amnestic MCI, who present with a subjective memory complaint, preferably corroborated by an informant, and have an objective memory impairment compared with age-matched healthy subjects. However, they perform well in tests of general cognitive function and have generally preserved activities of daily living. Nevertheless, these subjects are likely to progress to AD. In community-based studies, individuals with MCI are about 3 times more likely to develop AD than those without cognitive impairment, and this rate is somewhat higher in persons with amnestic MCI (Petersen et al., 2001, Grundman et al., 2004, Grundman et al., 2006). Other hypothetical presentations of MCI with slight impairments at multiple domains may progress to AD or VD, and those with single non-memory domain impairment might progress to frontotemporal dementia, Lewy body dementia, VD, primary progressive aphasia or Parkinson.s disease besides AD (Petersen et al., 2001, Dubois and Albert, 2004). Bennett et al. (2005) reported that in MCI several pathological findings similar to that of AD or cerebral infarctions were present and thus concluded that MCI might be the earliest clinical manifestation of age-related neurological diseases.

For clarity's sake, amnestic MCI is recommended to be used with its operational criteria, including (1) memory complaint, corroborated by an informant; (2) abnormal memory function; documented by delayed recall; (3) normal general cognitive function based on Clinical Dementia Rating (CDR) (Leonard, 1988) and Mini Mental State Examination (MMSE) (Folstein et al., 1975); (4) none or minimal impairments in activities of daily living (ADL); (5) not sufficiently impaired cognitively and functionally to meet NINCDS-ADRDA criteria for AD.

Several cognitive tests were applied both to MCI and AD patients to determine the specific cognitive dysfunctions in each pathology. Verbal learning and delayed recall tests proved to be useful for the detection of preclinical AD and MCI (Estevez-Gonzalez et al., 2003, Ivanoiu et al., 2005, Alladi et al., 2006), as well as several visual or other cognitive tasks, such as visual recognition, visuoconstructional performance, and semantic fluency (Malloy et al., 2003, Barbeau et al., 2004, Ribeiro et al., 2006).

Computerized neurocognitive batteries have been used in the evaluation of cognitive impairments both among AD and MCI patients. In MCI, dysfunctions were reported in memory, executive function, visual spatial skills, processing speed and cognitive flexibility (Dwolatzky et al., 2004, Gualtieri and Johnson, 2005).

The aim of our study was to compare cognitive dysfunctions in AD and MCI by a mean of a computerized test battery which may provide more objective results in the individual test than the classical neurocognitive tests. Furthermore, the computerized battery is language independent and also, as a visual test, it can be a useful tool to measure cognitive functions in patients with mild aphasia. The hypothesis was that the performance deficits of AD and MCI patients on the Cambridge Neuropsychological Automated Test Battery (CANTAB) might be similar, as MCI patients may already be in early stages of Alzheimer's disease. In early AD, novel therapeutic interventions are aimed at slowing the progression of the impairments and at delaying the onset of disability; thus, there is an increased need for diagnostic markers which may predict AD reliably.

Section snippets

Patient population

Two patients groups were entered into the study: dementia patients and non-demented patients with amnestic MCI. A detailed clinical examination was performed on all patients including cranial computed tomography (CT) or magnetic resonance imaging (MRI). The first patient group consisted of 15 demented patients (7 men, 8 women) with the diagnosis of probable dementia of Alzheimer type (AD) according to criteria of NINCDS-ADRDA and DSM-IV. The mean age (± SD) of the subjects was 58 ± 6 years (range:

Results

On all measures, the AD group performed significantly poorer than the healthy individuals or the MCI group, as shown in Fig. 1. The results of the individual tests for the two groups are given in Table 2.

Discussion

The present results show that several cognitive domains are already impaired in patients with MCI, and in AD patients several other cognitive domains show impairment and the severity of the cognitive dysfunctions is more pronounced.

Visual Paired Associate Learning (PAL test) was significantly (P < 0.05) impaired among subjects with AD and MCI. A successful performance in the PAL test requires both the elaboration of “frontal strategies” and the “mnemonic processes” of the medial temporal lobe (

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