The Fate of the 0.5s: Predictors of 2-Year Outcome in Mild Cognitive Impairment

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Journal of the International Neuropsychological Society (Impact Factor: 2.96). 12/2010; 17(2):277-88. DOI: 10.1017/S1355617710001621
Source: PubMed


Impairments in executive cognition (EC) may be predictive of incident dementia in patients with mild cognitive impairment (MCI). The present study examined whether specific EC tests could predict which MCI individuals progress from a Clinical Dementia Rating (CDR) score of 0.5 to a score ≥1 over a 2-year period. Eighteen clinical and experimental EC measures were administered at baseline to 104 MCI patients (amnestic and non-amnestic, single- and multiple-domain) recruited from clinical and research settings. Demographic characteristics, screening cognitive measures and measures of everyday functioning at baseline were also considered as potential predictors. Over the 2-year period, 18% of the MCI individuals progressed to CDR ≥ 1, 73.1% remained stable (CDR = 0.5), and 4.5% reverted to normal (CDR = 0). Multiple-domain MCI participants had higher rates of progression to dementia than single-domain, but amnestic and non-amnestic MCIs had similar rates of conversion. Only three EC measures were predictive of subsequent cognitive and functional decline at the univariate level, but they failed to independently predict progression to dementia after adjusting for demographic, other cognitive characteristics, and measures of everyday functioning. Decline over 2 years was best predicted by informant ratings of subtle functional impairments and lower baseline scores on memory, category fluency, and constructional praxis.

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    • "Neuropsychological testing informs the diagnosis of MCI and can assist in delineating specific MCI subtypes. This is important because individuals with amnestic multidomain (AMD) MCI have repeatedly been shown to have a poorer prognosis due to their increased risk for dementia [4] [5] [6]. A biomarker to complement the clinical and neuropsychological assessment of individuals with MCI and to assess their risk of conversion to dementia would be extremely useful [7]. "
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    ABSTRACT: A blood-based biomarker to complement the clinical and neuropsychological assessments used to evaluate the risk of individuals with mild cognitive impairment (MCI) developing Alzheimer's disease (AD) would be invaluable. Previous pilot studies by our group identified elevated platelet membrane β-secretase activity in patients with AD and MCI, as compared to controls, and this activity was influenced by membrane cholesterol levels. The present study investigated baseline platelet membrane β-secretase activity and cholesterol levels in 97 MCI participants and 85 controls and explored whether these parameters differed in individuals with stable MCI, as compared to those who subsequently developed AD. To evaluate signal specificity, β-secretase activity assays were conducted in the presence and absence of beta-site amyloid-β protein precursor-cleaving enzyme (BACE) inhibitors. Baseline platelet membrane β-secretase activity did not differ significantly in MCI participants, as compared to controls, and platelet membrane cholesterol levels were significantly lower in the MCI group. The longitudinal study indicated that the activities inhibited by two different BACE inhibitors did not predict conversion to AD; however, the activity that was not affected by BACE inhibitors was significantly (40%) higher in individuals with stable MCI, as compared with those who subsequently developed AD. These findings indicated that further research into the source of this activity could contribute to a measure facilitating prediction of the risk of conversion from MCI to AD.
    Preview · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
    • "In fact, more than half of the people (58.33%) who developed AD were classified as mMCI at their first assessment, versus other subtypes of MCI. Therefore, the presence of deficits in various cognitive domains (multidomain MCI) versus alteration in a sole domain (monodomain MCI) implies higher risk for the development of dementia (Aretouli et al., 2011; Baars et al., 2009; D ıaz- Mardomingo et al., 2010; Manly et al., 2008; Rasquin et al., 2005). "
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    ABSTRACT: In the field of neuropsychology, it is essential to determine which neuropsychological tests predict Alzheimer's disease (AD) in people with mild cognitive impairment (MCI) and which cut-off points should be used to identify people at greater risk for converting to dementia. The aim of the present study was to analyse the predictive value of the cognitive tests included in a neuropsychological battery for conversion to AD among MCI participants and to analyse the influence of some sociodemographic variables - sex, age, schooling - and others, such as follow-up time and emotional state. A total of 105 participants were assessed with a neuropsychological battery at baseline and during a 3-year follow-up period. For the present study, the data were analysed at baseline. During the follow-up period, 24 participants (22.85%) converted to dementia (2.79 ± 1.14 years) and 81 (77.14%) remained as MCI. The logistic regression analysis determined that the long delay cued recall and the performance time of the Rey figure test were the best predictive tests of conversion to dementia after an MCI diagnosis. Concerning the sociodemographic factors, sex had the highest predictive power. The results reveal the relevance of the neuropsychological data obtained in the first assessment. Specifically, the data obtained in the episodic verbal memory tests and tests that assess visuospatial and executive components may help to identify people with MCI who may develop AD in an interval not longer than 4 years, with the masculine gender being an added risk factor. © 2015 The British Psychological Society.
    No preview · Article · Mar 2015 · Journal of Neuropsychology
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    • "This task often activates the temporal lobe, a region broadly related to conceptualization, general information and knowledge about names (Patterson et al., 2007). Semantic verbal fluency contributes to predict future cognitive and functional impairments in the elderly (Salmon et al., 2002; Amieva et al., 2005; Hodges et al., 2006; Aretouli et al., 2011), and predict the progression from MCI to AD (Saxton et al., 2004). "
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    ABSTRACT: Semantic verbal fluency test is an important cognitive measure, broadly used in the neuropsychological assessment of the elderly, however its standards scores are less informative than what this task can provide. Graph theory represents a promising tool to understand a variety of neuropsychological states and this study presents a graph analysis of data generated by the semantic verbal fluency test in cognitive health elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI) - and Alzheimer’s disease (AD). The groups were compared when divided in three (NC – MCI – AD) and four groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, in the graph measures of diameter, the average shortest path, and on the density of the network. The graph measures also sorted the elderly in their groups with good specificity and sensitivity. When the four groups were compared the graph measures revealed significant difference between the groups in the density of the network, except between the two MCI subtypes and NC and aMCI. The diameter of the network and average shortest path were significant different between the NC and AD an aMCI and AD. Again the graph analysis sorted the elderly in their groups with good specificity and sensitivity, being better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of the semantic memory through the verbal fluency task, amplifying the predictive power of this test. The clinical use of graph analysis may likely give an important contribution to the differential diagnosis on elderly, helping in precocious diagnosis, and, consequently, improving prognosis.
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