A new scheme for the automatic assessment of Alzheimer's disease on a fine motor task with Transfer Learning.

We present a new scheme for Alzheimer's Disease (AD) automatic assessment, based on Archimedes spiral, drawn on a digitizing tablet. We propose to enrich spiral images generated from the raw sequence of pen coordinates with dynamic information (pressure, altitude, velocity) represented with a semi-global encoding in RGB images. By exploiting Transfer Learning, such hybrid images are given as input to a deep network for an automatic high-level feature extraction. Experiments on 30 AD patients and 45 Healthy Controls (HC) showed that the hybrid representations allow a considerable improvement of classification performance, compared to those obtained on raw spiral images. We reach, with SVM classifiers, an accuracy of 79% with pressure, 76% with velocity, and 70.5% with altitude. The analysis with PCA of internal features of the deep network, showed that dynamic information included in images explain a much higher amount of variance compared to raw images. Moreover, our study demonstrates the need for a semi-global description of dynamic parameters, for a better discrimination of AD and HC classes. This description allows uncovering specific trends on the dynamics for both classes. Finally, combining the decisions of the three SVMs leads to 81.5% of accuracy.Clinical Relevance- This work proposes a decision-aid tool for detecting AD at an early stage, based on a non-invasive simple graphic task, executed on a Wacom digitizer. This task can be considered in the battery of usual clinical tests.

Robot services for elderly with cognitive impairment: testing usability of graphical user interfaces.

BACKGROUND: Socially assistive robotics for elderly care is a growing field. However, although robotics has the potential to support elderly in daily tasks by offering specific services, the development of usable interfaces is still a challenge. Since several factors such as age or disease-related changes in perceptual or cognitive abilities and familiarity with computer technologies influence technology use they must be considered when designing interfaces for these users. OBJECTIVE: This paper presents findings from usability testing of two different services provided by a social assistive robot intended for elderly with cognitive impairment: a grocery shopping list and an agenda application. The main goal of this study is to identify the usability problems of the robot interface for target end-users as well as to isolate the human factors that affect the use of the technology by elderly. METHODS: Socio-demographic characteristics and computer experience were examined as factors that could have an influence on task performance. A group of 11 elderly persons with Mild Cognitive Impairment and a group of 11 cognitively healthy elderly individuals took part in this study. Performance measures (task completion time and number of errors) were collected. RESULTS: Cognitive profile, age and computer experience were found to impact task performance. Participants with cognitive impairment achieved the tasks committing more errors than cognitively healthy elderly. Instead younger participants and those with previous computer experience were faster at completing the tasks confirming previous findings in the literature. CONCLUSIONS: The overall results suggested that interfaces and contents of the services assessed were usable by older adults with cognitive impairment. However, some usability problems were identified and should be addressed to better meet the needs and capacities of target end-users.

DAD-6: A 6-ltem version of the Disability Assessment for Dementia scale which may differentiate Alzheimer's disease and mild cognitive impairment from controls.

BACKGROUND: The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). AIM: To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. METHODS: The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. RESULTS: DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84 (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33-0.75). CONCLUSION: The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.

Evaluation under real-life conditions of a stand-alone fall detector for the elderly subjects.

BACKGROUND AND OBJECTIVES: Elderly patients unable to get up after a fall or to activate an alarm mechanism are particularly at risk of complications and need to be monitored with extreme care. The different risk factors have fostered the development of stand-alone devices facilitating early detection of falls. We aimed at assessing performance of the Vigi'Fall(®) system, a cutting edge fall detector associating a "passive release" mechanism attached to the patient and including external sensors; in the event of a fall, the system automatically triggers an alarm, and it also incorporates embedded confirmation software. We have put it to the test under real-life conditions so as to evaluate not only its efficacy, but also and more particularly its acceptability and tolerability in elderly subjects. METHOD: The study ran from March 2007 through December 2008 in a geriatric ward with 10 subjects over 75 years of age, all of whom presented with a risk of falling. RESULTS: For eight patients wearing an accelerometric sensor, eight "falling" events and 30 "alarm release" events were recorded. Sensitivity and specificity of the device came to 62.5 and 99.5% respectively. For the two patients wearing the complete device, no events were detected. Not a single adverse occurrence was noted. Local tolerance was excellent in all but one of the subjects. CONCLUSION: Our results clearly show that the device may be worn by patients without discomfort over prolonged periods of time, and also demonstrate that the verification component will help to increase sensitivity in real-life conditions to a level comparable to the level attained in our laboratory studies.

Regional differences in effects of APOE ε4 on cognitive impairment in non-demented subjects.

BACKGROUND: The APOE ε4 allele is a risk factor for Alzheimer's disease (AD). APOE ε4 is common in non-demented subjects with cognitive impairment. In both healthy people and people with AD, its prevalence has a north-south gradient across Europe. In the present study, we investigated whether the relation between the APOE ε4 allele and cognitive impairment varied across Northern, Middle and Southern Europe. We also investigated whether a north-south gradient existed in subjects with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (MCI) and non-amnestic MCI. METHODS: Data from 16 centers across Europe were analyzed. RESULTS: A north-south gradient in APOE ε4 prevalence existed in the total sample (62.7% for APOE ε4 carriers in the northern region, 42.1% in the middle region, and 31.5% in the southern region) and in subjects with SCI and amnestic MCI separately. Only in Middle Europe was the APOE ε4 allele significantly associated with poor performance on tests of delayed recall and learning, as well as with the amnestic subtype of MCI. CONCLUSION: The APOE ε4 allele frequencies in subjects with SCI and amnestic MCI have a north-south gradient. The relation between the APOE ε4 allele and cognition is region dependent.

Episodes of falling among elderly people: a systematic review and meta-analysis of social and demographic pre-disposing characteristics

CONTEXT: The multifactorial nature of falls among elderly people is well-known. Identifying the social-demographic characteristics of elderly people who fall would enable us to define the typical profile of the elderly who are at risk of falling. OBJECTIVE: We aimed to isolate studies in which the social-demographic risk factors for falls among the elderly have been evaluated and to carry out a meta-analysis by combining the results of all of these selected studies. METHOD: We did a systematic literature review using the key words "accidental fall / numerical data" and "risk factors." Inclusion criteria entailed the selection of articles with the following characteristics: population of subjects aged 60 years or over, falls that took place in everyday life, and social-demographic risk factors for falls. RESULTS: 3,747 indexed articles published between 1981 and 2007 were identified, and 177 studies with available data were included, of which 129 had data on social-demographic risk factors for falls. Difficulties in activities of daily living (ADL) or in instrumental activities of daily living (IADL) double the risk of falling: The OR and 95 percent Cl were 2.26 (2.09, 2.45) for disturbance ADL and 2.10 (1.68, 2.64) for IADL. The OR and 95 percent Cl for Caucasians were 1.68 (0.98 - 2.88) and 0.64 (0.51 - 0.80) for Hispanics. In the subgroup of patients older than eighty, being married protected people from falling with an OR and 95 percent Cl =0.68 (0.53 - 0.87). CONCLUSION: Defining factors that create a risk of falling and protect elderly people from falls using social-demographic characteristics lets us focus on an "at risk" population for which a specific program could be developed.

Electronic tracking system and wandering in Alzheimer's disease: a case study.

INTRODUCTION: Wandering is a behavioural disorder, which occurs in Alzheimer's disease or other dementia. People who wander are at risk of physical harm and untimely death. Moreover, wandering behaviour causes a lot of stress to the caregivers. In the last few years, different geolocation devices have been developed in order to minimise risk and manage unsafe wandering. These detection systems rarely meet patients and caregivers' needs because they are not involved in the devices building process. AIM: The aim is to explore the needs and perceptions of wandering persons and their caregivers towards existing tracking devices as well as their acceptability and usability. This paper reports a dyad case. MATERIALS: The tracking system tested is presented as a mobile Global Positioning System (GPS) receiver-shaped, including function of telephony and data transfer via GSM/GPRS. METHOD: Dyad patient/caregiver expressed their needs and perceptions towards tracking devices and gave their impressions about the functioning of the tested device at the end of the test. RESULTS: The patient focused on the device's shape which he found too voluminous and unaesthetic, and was unable to give an opinion about the device's functioning. The spouse highlighted malfunctions and usage difficulties, which made the device not appropriate to her needs. CONCLUSION: Involving end-users in the co-design of new technologies is necessary for building tailored devices. Moreover, in this area of dementia care, the person-centred approach is essential to a tailored wandering management.

Development of screening guidelines and clinical criteria for predementia Alzheimer's disease. The DESCRIPA Study.

BACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.

[Relationship of white matter lesions on brain computed tomography and cognitive function in elderly subjects with mild cognitive impairment]. / Relations entre troubles cognitifs et lésions de la substance blanche cérébrale.

UNLABELLED: White matter lesions (WML) are frequently disclosed on elderly people computed tomography (CT) brain scan. OBJECTIVE: To evaluate the relationship between WML and cognitive functions of patients suffering from Mild Cognitive Impairment (MCI). METHODS: We studied the association between WML on CT brain scan and cognitive functions in 136 consecutive elderly subjects attending a geriatric outpatient clinic, suffering from MCI. The global cognitive assessment was based on Mini Mental State Examination (MMSE), a validated comprehensive battery of neuropsychological tests, the Cognitive Efficiency Profile (CEP), a CT brain scan and a complete biological screening. WML on CT brain scan was evaluated by a blinded investigator. RESULTS: In this population, 75 +/- 8 years of age, (women 60%, and hypertension 54%), 33% of subjects had WML on CT brain scan. Patients with WML were significantly older (OR=1.27; IC 95%=1.04 - 1.22), had more frequently a past history of hypertension (OR=2.71; IC 95%=1.06 - 6.96) and more frequently lacunae associated with WML (OR=4.48; IC 95%=1.18 - 16.99). Subjects with WML had significantly poorer cognitive functions than those without WML (CEP score/100=62.33 +/- 13.58 versus 71.87 +/- 14.19, p<0.01 and MMSE score/30=27.02 +/- 2.34 versus 27.97 +/- 1.89, p<0.01) CONCLUSION: Our results showed a relationship between WML on CT brain scan and the depth of cognitive dysfunction among MCI patients. Further long term prospective studies have to be performed to determinate if WML are involved in transitions between MCI and Alzheimer' s disease.

[What is the most relevant definition of orthostatic hypotension: systolic blood pressure drop, diastolic blood pressure drop, or both?]. / Quelle baisse de pression artérielle choisir pour définir l'hypotension orthostatique chez le sujet âgé: Chute de la pression artérielle systolique, de la diastolique ou des deux?

UNLABELLED: The agreed definition of orthostatic hypotension (OH) is a drop of 20 mmHg systolic and/or 10 mmHg diastolic blood pressure (BP) within the first 3 min of erect posture. For elderly people, a question can be raised about diastolic BP relevance in OH's definition. OBJECTIVE: To determinate HO's prevalence and risks factors considering systolic blood pressure (SBP)'s drop, or diastolic blood pressure (DBP)'s drop, or either. METHODS: We assessed OH for 554 consecutive, ambulatory, elderly subjects, attending a geriatric outpatient clinic. OH was defined as a SBP drop>20mmHg (SBP-OH), or a DBP drop>10 mmHg (DBP-OH), or a drop in either (SBP. DBP-OH). OH's prevalence and risks factors were determined. RESULTS: In this population, 76 +/- 6 years of age, (70% hypertension), SBP-OH's prevalence was 17%, DBP-OH's prevalence was 12% and SBP. DBP-OH's prevalence was 25%. OH's risks factors varied considering OH's definition. After adjusting for significant determinants, SBP-OH's risk factors were: Antihypertensive therapy (OR=2.95; IC 95%: 1.21-4.04), age>75years (OR=2.11; IC 95%: 1.22-3.66), anti-hypertensive poly therapy (OR=2.01; IC 95%: 1.39-2.92) and SBP level (OR=1.16; IC 95%: 1.01-1.33). Considering DBP-OH, the only significant risk factor was DBP's level (OR=2.64; IC 95%: 1.89-3.68). SBP. DBP-OH was only determined by anti-hypertensive poly therapy (OR=1.61; IC 95%: 1.13-2.29) and DPB level (OR=1.32; IC 95%: 1.08-1.60). CONCLUSION: For elderly people, OH's prevalence and risks factors vary considering OH's definition. SBP's drop seems to be more relevant than DBP's drop. A long term follow up is necessary to determine if SBP-OH is correlated with HO' s side effects and to establish the dangerous level of SBP' s drop.

[Neuropsychological impairment in the early Alzheimer's disease]. / Le déficit neuropsychologique dans la maladie d'Alzheimer débutante.

This analysis is centered on the study of cognitive disorders in Alzheimer's disease (AD), mainly for major neuro-psychological functions. We insist on the heterogeneity of the clinical picture peculiarly in the early stages of the illness, even if the deficits of episodic memory and of attentional/executive capacities are the first to deteriorate, preceding impairment in perceptual and language function and potentially having a substantial impact on the patient's capacity to cope independently. An episodic memory deficit is the hallmark of AD, but it must be stressed that this deficit may take different forms and its origin may be traced back to different cognitive mechanisms. One of the most striking aspects of episodic memory impairment in AD is the rapidity of forgetfulness on which screening and diagnostic tests of AD are based. There is some evidence that the episodic memory deficit in AD is one of learning (encoding and storage) of information rather than to a deficit of retrieval. Furthermore, episodic memory performance in AD depends on the integrity of semantic memory abilities, so giving support to a hierarchical model of organization of human memory. Finally, recent results show that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Executive deficits appear predominantly in tasks requiring cognitive flexibility and self-monitoring. With the progression of the disease, additional deficits are observed in the verbal concept formation abilities. These findings might be also very useful in the differential diagnosis between AD and the other cortical and subcortical dementias, as well as in the differentiation between AD and fronto-temporal dementia. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline. Recent research suggested that onset of AD is commonly preceded by an interim phase known as mild cognitive impairment (MCI). MCI refers to the clinical condition in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. Persons who experience this condition are at increased risk for the development of AD. In MCI, despite the comparable global cognitive functioning, the findings show more impaired retrieval from long-term storage than in NC. The cued recall improves slightly the total recall but the recognition is significantly impaired. Moreover, the data indicate that MCI patients had additional problems with response inhibition, switching and cognitive flexibility. This suggests, that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone. As preventive strategies are developed and new cognitive enhancing therapies emerge, these results may also help us to define which domains are expected to improve in MCI populations.

Relevance of 10-min delayed recall in dementia screening.

Within the context of early diagnosis of Alzheimer's disease (AD), there is a growing interest in neuropsychological screening tests. Amongst these tests, we focused on the largely used Memory Impairment Screen (MIS). The objective of the present work was to show that adding a 10-min delayed recall to the MIS, improves the test psychometric characteristics in order to detect dementia in the earliest stages. A prospective study was carried out on a cohort of 270 consecutive elderly ambulatory subjects attending the Broca Hospital Memory Clinic: normal controls (n = 67), mild cognitive impairment subjects (n = 98) and mildly demented patients [n = 105, Mini Mental State Examination (MMSE) = 23 +/- 4]. This study consisted in testing the advantage of the 10-min delayed recall entitled MIS-D compared with the MIS. At a cut-off score of 6, the MIS-D revealed satisfying psychometric characteristics with a sensitivity of 81% and a specificity of 91%, whilst the MIS alone indicated a sensitivity of 60% and a specificity of 88% in detecting dementia. In demented patients with MMSE score > or =26, MIS-D properties still remained satisfying (sensitivity: 75%, specificity: 92%). MIS-D is a more relevant screening test than MIS alone at very early stages of dementia.

[Alzheimer's disease: cardiovascular risk factors must be assessed]. / Maladie d'Alzheimer: prendre en compte les facteurs de risque et pathologies cardiovasculaires.

BACKGROUND: Dementia is nowadays of major importance in public health. Alzheimer's disease and vascular cognitive impairments are its main aetiology in the elderly. The cause of Alzheimer's disease remains unknown. The factor initiating the physiopathology of this neurodegenerative disease is source of controversy. CURRENT KNOWLEDGE AND KEY POINTS: The theory of a neurotoxicity initiated by amyloid deposition is questioned. A growing number of data suggest a central role of cardiovascular risk factors and alteration of arterial walls, inducing chronic brain hypoperfusion, as the primary trigger in the physiopathology of the disease. These data are based on epidemiological, physiopathological, neuroimaging, neuropathological and pharmacological studies. However, the exact link between arteriosclerosis, vascular cognitive impairment and Alzheimer's disease remains controversial. FUTURE PROSPECTS AND PROJECTS: These debates point out the crucial importance of the assessment of cardiovascular risk factors, as a preventable cause, either of cognitive decline, morbidity and mortality. In this aim, major targets could be different when primary or secondary prevention are at stake. These controversies also suggest new research directions towards Alzheimer's disease physiopathology, and for pharmacological interventions aimed on the prevention of cognitive decline or the curative treatment for this disease.

[Consensus statement on severe dementia]. / Consensus sur la démence de type Alzheimer au stade sévère.

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

Accidental MCI in healthy subjects: a prospective longitudinal study.

A study was realized on 130 healthy and autonomous volunteers (60-80 years old) who met specific medical and functional inclusion criteria. A comprehensive battery of neuropsychological tests was performed at baseline (M0), 6 and 12 months (M6, M12). At M0 the results indicated that 65% were cognitively normal on each of all the neuropsychological tests, whereas 35% presented a cognitive deficit on one or more tests. At M12, 52% of the subjects who had a cognitive deficit at M0 remained impaired, whereas 48% normalized their scores: they performed as well as the subjects classified normal at M0. The results also indicated that the subjects who remained impaired at M12, had at M0 low scores on three tests or more, whereas the ones who normalized their scores had one or two failed tests. This study focuses on the risk of false positive cases and shows that low scores can be accidental. The authors propose decision rules allowing to reduce the risk of false positive cases. The observation of accidental impairment invites to be cautious and makes this 1-year follow-up study particularly relevant, since a 1-year follow-up is generally needed to diagnose very mild dementia.