Telemedicine for neurological diseases: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases. METHODS: The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated. RESULTS: Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up. CONCLUSIONS: Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases.

The Vallecas Project: A Cohort to Identify Early Markers and Mechanisms of Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers) may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. METHODS: We launched the Vallecas Project (VP), a cohort study of non-demented people aged 70-85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. RESULTS: A total of 1169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9), 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI) 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI). Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for 4 years after the baseline. CONCLUSION: We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

Clinical and anatomical correlates of gait dysfunction in Alzheimer's disease.

We conducted a cross-sectional study to investigate the clinical and anatomical correlates of gait dysfunction in advanced Alzheimer's disease (AD). A comprehensive clinical protocol that included cognitive, functional, behavioral, and motor variables was administered to patients with probable AD (n = 100), possible AD (n = 17), and AD with cerebrovascular disease (AD + CVD) (n = 27). Gait dysfunction was evaluated with the Rating Scale for Gait Evaluation in Cognitive Deterioration and magnetic resonance imaging was analyzed in 94 patients (volumetry study) and 78 patients (diffusion tensor imaging study). Univariate correlations, multivariate regression, and statistical parametric mapping analyses were conducted in the total sample and in the subsample of patients with probable AD. Mean age was 82.5 (SD 6.3, range 56 to 98), 83.3% were female patients, and 95.1% displayed moderate to severe dementia. Parkinsonism, patient setting (nursing home), dementia severity, apathy, and (worse) cognitive performance significantly predicted gait dysfunction in the total sample (p < 0.05, R(2) = 0.58), whereas parkinsonism, patient setting, and limb weakness due to non-AD conditions predicted gait dysfunction in probable AD (p < 0.05, R(2) = 0.57). Gait dysfunction was related to atrophy in the motor cortex, the middle cingulate, the anterior insula, the right caudate (total sample only), and the anterior lobe of the cerebellum (p < 0.01, corrected). Significant correlations were also observed between gait dysfunction and damage in several white matter locations (p < 0.001, uncorrected). The present results are congruent with a model of multi-system gray matter degeneration, with progressive damage to critical regions (i.e., motor cortex, cingulate, insula, and cerebellum) producing gait dysfunction and, eventually, gait loss in AD.

Quality of life (QoL) in community-dwelling and institutionalized Alzheimer's disease (AD) patients.

The purpose of this study was to describe and compare QoL and its determinants in two groups of patients with AD that differed in place of residence: community or nursing home. This study covered 200 patients with AD (mean age 79.3 ± 8.2 years, 74% female). Fifty-four per cent of the subjects were living in a nursing home and 46% lived at home. QoL was measured using the Alzheimer's Disease Related Quality of Life Scale (ADRQL). The ADRQL was answered by the family caregiver (community group) or the professional caregiver (nursing home group). Descriptive statistics, Chi-square test, Mann-Whitney test and multiple regression analysis were used to compare sociodemographic and clinical variables between the two study groups. The institutionalized patients were predominantly women (87.0% vs. 58.7%, p<0.001), were older (84 years vs. 74 years, p<0.001), and had more advanced dementia (Global Deterioration Scale (GDS)>5 79.6% vs. 19.6%, p<0.001). ADRQL total score was higher (i.e., better QoL) for patients living at home than for institutionalized patients (72.6 ± 19.9 vs. 64.8 ± 18.2, p<0.01). Neuropsychiatric symptoms, severity of dementia, depression and functional dependence were significant predictors of worst QoL. Once those variables were controlled a marginal effect of setting on QoL was found, which favored the nursing home (ß=0.20, p<0.05).

Promoting research in advanced dementia: early clinical results of the Alzheimer Center Reina Sofía Foundation.

The Alzheimer Center Reina Sofía Foundation (ACRSF) was envisaged to address the complex and multi-disciplinary research and care needs posed by Alzheimer's disease (AD) and other neurodegenerative dementias. Patients may be admitted at ACRSF either as inpatients (i.e., nursing home) or outpatients (i.e., day-care center). The research program includes clinical, social, biochemical, genetic, and magnetic resonance investigations, as well as brain donation. We present the inception of the clinical research protocol for the ACRSF, the early results, and the amendments to the protocol. Foreseen as distinct populations, inpatient and outpatient results are presented separately. Data were collected from 180 patients (153 inpatients, 27 outpatients) (86% AD), with informed consent for participation in the research program of the ACRSF. Most patients (95%) had moderate to severe dementia. Nursing home patients were older, displayed marked gait dysfunction, and were significantly more dependent in the activities of daily living (ADL), compared to the day-care patients (p < 0.05). Some cognitive, ADL, and quality of life (QoL) scales were eliminated from the protocol due to floor effect or lack of specificity of contents for advanced dementia. New measurements were added for evaluation of cognition, apathy, agitation, depression, ADL, motor function, and QoL. The final assessment is expected to be sensitive to change in all the clinical aspects of advanced degenerative dementia, to promote multidisciplinary and, desirably, inter-center collaborative research and, eventually, to contribute to the improvement of treatment and care for these patients.

Genetic variation in the tau kinases pathway may modify the risk and age at onset of Alzheimer's disease.

Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in the Alzheimer's disease (AD) brain is the result of upregulation of tau kinases. In a group of 729 Spanish late-onset AD patients and 670 healthy controls, we examined variations into a set of 20 candidate genes of kinases involved in tau phosphorylation at AD-related sites (PRKACB; CAMK2A; MARK1, 2, 3 and 4; CSNK1D; CDC2; RPS6KB1 and 2; p38α and ß; IB1; JNK1, 2 and 3; MEK1 and 2; ERK1 and 2), to address hypotheses of genetic variation that might influence both AD risk and age at disease onset. There was an increased frequency of RPS6KB2 (intron 2, rs917570) minor allele in patients (50%) versus controls (39%) (OR = 1.52; 95% CI 1.30-1.77; p = 1.24 × 10-5 Bonferroni corrected), and the presence of this minor allele was significantly (p = 4.2 × 10-5) associated with a 3-years later onset of AD (mean age 74.1 years) when compared to age at onset of non-minor allele carriers (mean age 71.1 years). In APOE non-ε4 allele carriers, the combined effect of AD-associated risk alleles from the genes of CDC2, RPS6KB1 and 2, p38α, JNK (1, 2 and 3), MEK2, and ERK2 was significantly (p = 0.002) associated with a late-onset (>76 years) of AD. The CDC2 AGC haplotype derived from SNPs in introns 3 (rs2448347), 5 (rs2456772), and 7 (rs1871447) showed a protective effect against AD in APOE non-ε4 allele carriers (permutation p = 1.0 × 10-4) with a frequency of 9% in cases and 15% in controls. Common genetic variation in the tau kinases pathway does underlie individual differences not only in susceptibility to AD but also in disease phenotype (age at disease onset).