Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study

BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline

Estimated pre-morbid IQ effects on cognitive and functional outcomes in Alzheimer disease: a longitudinal study in a treated cohort

Abstract Background 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. Methods 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. Results 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 Conclusion 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.</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Screening for mild cognitive impairment: a systematic review.

OBJECTIVE: Patients with mild cognitive impairment account for a significant number of referrals to old age psychiatry services and specialist memory clinics. The cognitive evaluation of such patients is commonly restricted to brief dementia screens, with no consideration to their suitability for assessing MCI. Here, we review the utility of such cognitive screens for MCI and provide an overview of validated instruments. METHODS: We identified papers published after Petersen and colleagues 1999 MCI criteria (Petersen et al., 1999) and examining face-to-face cognitive screening for MCI from publication databases using combinations of the search terms 'mild cognitive impairment' and 'cognitive screening'. We also combined the former search with the names of 39 screening tests recently identified in a relevant review (Cullen et al., 2007). RESULTS: Fifteen cognitive screening instruments were identified, 11 cover a restricted range of cognitive domains. High sensitivity and specificity for MCI relative to healthy controls were reported for two comprehensive and two noncomprehensive screening instruments, adequate test-retest and inter-rater reliability for only one of these. With the exception of three studies, sample sizes were universally small (i.e. n </= 100), and prognostic values were reported for only two of the identified 15 screening measures. Sensitivities of the full domain measures were universally high, but information about their specificity against psychiatric and non-progressive neurological conditions and predictive validity is lacking. CONCLUSION: Several cognitive screening instruments afford the clinician the ability to detect MCI, early AD, and in some cases non-AD dementia, but they cannot currently be used to make reliable inferences about the course and eventual outcome of MCI

Clinical referral patterns and cognitive profile in mild cognitive impairment.

BACKGROUND: There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile. AIMS: To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype. METHOD: Consecutive tertiary referrals (n=187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination. RESULTS: Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment. CONCLUSIONS: Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment

MRI correlates of episodic memory in Alzheimer's disease, mild cognitive impairment, and healthy aging.

Episodic memory is a core feature of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Impaired episodic memory in AD results from the dysfunction of an integrated network and involves both gray and white matter pathologies. We explored the neural correlates of episodic memory in AD, MCI and healthy aging by correlating a measure of episodic memory with hippocampal volume and fractional anisotropy (FA) and mean diffusivity (MD) of the cingulum and fornix. Episodic memory was associated with hippocampal volume and MD of the cingulum and fornix. In contrast, there were fewer significant associations between episodic memory and FA. These findings support a relationship between episodic memory and hippocampal circuitry, and suggest that MD is a more sensitive marker of decreased white matter integrity in the study of AD and MCI than FA. Furthermore, MD was significantly associated with hippocampal volume, indicating that white matter pathology is not completely independent of gray matter pathology. However, the pattern of diffusivity differences in AD and MCI implies a more complex pathology than simply Wallerian degeneration