Elderly Alzheimer's Disease Patients Research Articles

Insights on benzodiazepines' potential in Alzheimer's disease.

Alzheimer's disease (AD) is the most frequent type of dementia characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. AD is associated with the disturbances of various neurotransmitters including gamma-aminobutyric acid (GABA). Of note, GABA is reduced in AD, and restoration of GABA effect by benzodiazepines (BDZs) may improve AD outcomes. However, BDZs may adversely affect cognitive functions chiefly in elderly AD patients with sleep disorders. Besides, there is a controversy regarding the use of BDZs in AD. Consequently, the objective of the present review was to disclose the possible role of BDZs on the pathogenesis of AD that might be beneficial, neutral, or detrimental effects on AD. Prolonged use of intermediate-acting BDZ lorazepam exerts amnesic effects due to attenuation of synaptic plasticity and impairment of recognition memory. However, BDZs may have a protective effect against the development of AD by reducing tau phosphorylation, neuroinflammation, and progression of AD neuropathology. On the other side, other findings highlighted that extended use of BDZs was not associated with the development of AD. In conclusion, there are controversial points concerning the use of BDZs and the risk for the progression of AD. Thus, preclinical, and clinical studies are essential in this regard.

Knowledge, attitude and practice of caregiver of the elderly with Alzheimer's regarding this disease in Yazd city, 1400

Introduction: Along with the increase in the elderly population, caring for the elderly with Alzheimer's disease has become a challenge in the field of their health and well-being. Also, the need for caregivers is increasing due to the lengthening of the care period. Considering that the nurses of Alzheimer's patients play the main role in providing services to the elderly, the present study was conducted with the aim of determining the state of knowledge, attitude and practice of the caregiver of elderly Alzheimer's patients in Yazd city.
 Methods: This study was descriptive. The sample size was 60 caregiver of elderly people with Alzheimer's disease in Yazd city. The sampling method in this study was based on the vailability of statistical research and consulting facilities. The data collection tool in this study was a four-part questionnaire (demographic, knowledge, attitude and practice) that was used in a similar study. Data were analyzed with spss24 software and using descriptive statistics as well as t-test and Anova.
 Results: The average age score of nurses was 62.73 ± 11.78. The average score of knowledge, attitude and practice of elderly caregiver were 21.58 ± 1.87, 35.65 ± 2.84 and 12.57 ± 1.28, respectively. The data showed that there is a significant relationship between the knowledge score and family ratio and previous experience of care. Also, there is a significant relationship between attitude score and previous care experience (P≤0.05).
 Conclusion: Considering the importance of caregivers' knowledge of the phenomenon of aging and Alzheimer's disease, it is suggested to provide appropriate training to improve the knowledge and change the attitude of caregivers of the elderly in order to improve the quality and provide better and more suitable services for the elderly.

Structural But Not Functional Connectivity Differences within Default Mode Network Indicate Conversion to Dementia.

Malfunctioning of the default mode network (DMN) has been consistently related to mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, evidence on differences in this network between MCI converters (MCI-c) and non-converters (MCI-nc), which could mark progression to AD, is still inconsistent. To multimodally investigate the DMN in the AD continuum. We measured gray matter (GM) volume, white matter (WM) integrity, and functional connectivity (FC) at rest in healthy elderly controls, MCI-c, MCI-nc, and AD patients, matched on sociodemographic variables. Significant differences between AD patients and controls were found in the structure of most of the regions of the DMN. MCI-c only differed from MCI-nc in GM volume of the left parahippocampus and bilateral hippocampi and middle frontal gyri, as well as in WM integrity of the parahippocampal cingulum connecting the left hippocampus and precuneus. We found significant correlations between integrity in some of those regions and global neuropsychological status, as well as an excellent discrimination ability between converters and non-converters for the sum of GM volume of left parahippocampus, bilateral hippocampi, and middle frontal gyri, and WM integrity of left parahippocampal cingulum. However, we found no significant differences in FC. These results further support the relationship between abnormalities in the DMN and AD, and suggest that structural measures could be more accurate than resting-state estimates as markers of conversion from MCI to AD.

European Projects for Patients with Dementia and Their Caregivers.

As we all know there is no treatment that can stop or delay the progression of dementia. The treatment we use is only symptomatic. EFNS (European Federation of Neurological Societies) recommendations for dementia prevention by Sorbi et al. (2012) concluded that there is no treatment, no lifestyle, which could have an effect on prevention or delay of onset of different forms of dementia until today. The future studies in prevention must recruit younger people, larger sample, and for longer period. The last 10years we have run, in collaboration with organizations in different European countries, many projects in order to support patients with neurodegenerative diseases, mainly patients with dementia and their caregivers. The first project was a 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease (AD) in Europe: predictors of discontinuation and switch in the ICTUS (Impact of Cholinergic Treatment USe) study, an FP5 project with 1380 patients. Five studies were published. The second project was DESCRIPA study, an FP5 project to DEvelopment of Screening guidelines and clinical CRIteria for Predementia Alzheimer's disease, with 881 patients with mild cognitive impairment (MCI). LLM (Long Lasting Memories) and VRADA (A virtual reality application for the exercise of dementia and Alzheimer patients) are two projects that include body and cognitive exercise for health for the elderly and patients with mild cognitive impairment. The next is the RECAGE (REspectful Caring for the AGitated Elderly) project (Horizon 2020), a prospective cohort study for coping with behavioral and psychological symptoms of dementia. With six European universities we finished a very interesting FP6 project, the AddNeuroMed one, which gives even now information about the progression of normal elderly MCI and AD patients, in collaboration with other consortia. A very interesting Innovative Medicines Initiative (IMI) project about digital biomarkers was entitled Remote Assessment of Disease and Relapse-Alzheimer's Disease (RADAR project). The main goal of this project was the development and validation of technology-enabled, quantitative and sensitive measures of functional decline in people with early-stage AD. A running project is an Erasmus+ one in the higher education field, "Genetic counseling in European universities: The case of neurodegenerative diseases" (GECONEU project). The target of this study is to develop an online course for university students focusing on genetic counseling, and support people and society to better understand the aims of genetic testing and the usefulness of genetic counseling by involving students in an innovative learning and teaching setting. AD-gaming, BRIDGE, iCONNECT (Intergenerational CONtact between studeNts and people with dEmentia through CreaTive education), E.L.So.M.C.I (English Lessons with the Use of Songs for People with Mild Cognitive Impairment), Games4CoSkills, and De-Sign are all Erasmus+ projects that aim to improve the quality of life of patients with MCI or dementia. Story2remember, Dementia right, ASPAD (Augmentation of the Support of Patients suffering from Alzheimer's Disease and their caregivers), INFOCARE (Supporting Informal Caregivers of People with Dementia), S.IN.CA.L.A (Supporting Informal Carers: A Whole-Family and Life course Approach), and PIA (Peer support workers as an Innovative force in Advocacy in dementia care) are all Erasmus+ projects for training and supporting caregivers of patients with dementia.

Presynaptic membrane protein dysfunction occurs prior to neurodegeneration and predicts faster cognitive decline.

Although presynaptic loss measured by cerebrospinal fluid (CSF) growth-associated protein-43 (GAP-43) is significantly involved in Alzheimer's disease (AD), the sequential association between CSF GAP-43 and AD-typical neurodegeneration is poorly understood. We compared baseline CSF GAP-43 levels (n=730) and longitudinal CSF GAP-43 changes (n=327) in various biological stages of AD, and investigated their relationships with cross-sectional and longitudinal measures of residual hippocampal volume, 18 F-fluorodeoxyglucose PET, regional gray matter volume and cortical thickness, and cognition. Elevated CSF GAP43 levels were significantly associated with faster rates of hippocampal atrophy, AD-signature hypometabolism and cortical thinning, and middle temporal gray matter atrophy-related and AD-signature hypometabolism-related cognitive decline. In contrast, baseline levels of all these neurodegeneration biomarkers did not predict longitudinal CSF GAP-43 increases. These findings suggest that presynaptic loss may occur prior to neurodegeneration, highlighting the importance of lowing tau aggregation and tau-related synaptic dysfunction in elderly adults and AD patients.

A New Early Warning Method for Human-Computer Interaction of Alzheimer's Disease Patients Based on Deep Learning

Alzheimer's disease (AD), an incurable disease, poses a major health problem. It is important to identify patients with mild cognitive impairment (MCI) and early AD. Clock rendering test (CDT) is an effect way to screen AD patients quickly in the community. However, the current CDT methods require specific equipment to collect features, and the existing prediction models are inefficient in early warning of MCI. To solve the problem, this paper replaces digital pen with fingertip interaction, and proposes an early warning model for AD early dCDT images based on ResNet50. The dCDT tests were carried out on normal cognitive elderly, MCI patients and mild AD patients, and the results were used to verify the analysis and classification ability of the ResNet50-based early AD prediction model, in contrast to the clock score-based early AD prediction model. The comparison shows that the ResNet50-based early AD prediction model is efficient in early warning than the other model, and is suitable for large-scale screening of AD patients in the community, in the absence of doctors.

Glucose enrichment impair neurotransmission and induce Aβ oligomerization that cannot be reversed by manipulating O-β-GlcNAcylation in the C. elegans model of Alzheimer's disease

Amyloid beta (Aβ) plaques formation and impaired neurotransmission and neuronal behaviors are primary hallmarks of Alzheimer's disease (AD) that are further associated with impaired glucose metabolism in elderly AD's patients. However, the exact role of glucose metabolism on disease progression has not been elucidated yet. In this study, the effect of glucose on Aβ-mediated toxicity, neurotransmission and neuronal behaviors has been investigated using a C. elegans model system expressing human Aβ. In addition to regular diet, worms expressing Aβ were supplemented with different concentrations of glucose and glycerol and 5 mM 2-deoxyglucose to draw any conclusions. Addition of glucose to the growth medium delayed Aβ-associated paralysis, promoted abnormal body shapes and movement, unable to restore impaired acetylcholine neurotransmission, inhibited egg laying and hatching in pre-existing Aβ-mediated pathology. The harmful effects of glucose may associate with an increase in toxic Aβ oligomers and impaired neurotransmission. O-β-GlcNAcylation (O-GlcNAc), a well-known post-translational modification is directly associated with glucose metabolism and has been found to ameliorates the Aβ- toxicity. We reasoned that glucose addition might induce O-GlcNAc, thereby protect against Aβ. Contrary to our expectations, induced glucose levels were not protective. Increasing O-GlcNAc, either with Thiamet-G (TMG) or by suppressing the O-GlcNAcase (oga-1) gene does interfere with and, therefore, reduce Aβ- toxicity but not in the presence of high glucose. The effects of glucose cannot be effectively managed by manipulating O-GlcNAc in AD models of C. elegans. Our observations suggest that glucose enrichment is unlikely to be an appropriate therapy to minimize AD progression.

Structural differences in amyloid-β fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients

Although amyloid plaques composed of fibrillar amyloid-β (Aβ) assemblies are a diagnostic hallmark of Alzheimer's disease (AD), quantities of amyloid similar to those in AD patients are observed in brain tissue of some nondemented elderly individuals. The relationship between amyloid deposition and neurodegeneration in AD has, therefore, been unclear. Here, we use solid-state NMR to investigate whether molecular structures of Aβ fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of Aβ fibrils from AD tissue. Two-dimensional solid-state NMR spectra of isotopically labeled Aβ fibrils, prepared by seeded growth from frontal lobe tissue extracts, are similar in the two cases but with statistically significant differences in intensity distributions of cross-peak signals. Differences in solid-state NMR data are greater for 42-residue amyloid-β (Aβ42) fibrils than for 40-residue amyloid-β (Aβ40) fibrils. These data suggest that similar sets of fibril polymorphs develop in nondemented elderly individuals and AD patients but with different relative populations on average.

Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer's disease

Impaired memory is a hallmark of prodromal Alzheimer's disease (AD). Prior knowledge associated with the memoranda improves memory in healthy individuals, but we ignore whether the same occurs in early AD. We used functional MRI to investigate whether prior knowledge enhances memory encoding in early AD, and whether the nature of this prior knowledge matters. Patients with early AD and Controls underwent a task-based fMRI experiment where they learned face-scene associations. Famous faces carried pre-experimental knowledge (PEK), while unknown faces with which participants were familiarized prior to learning carried experimental knowledge (EK). Surprisingly, PEK strongly enhanced subsequent memory in healthy controls, but importantly not in patients. Partly nonoverlapping brain networks supported PEK vs. EK associative encoding in healthy controls. No such networks were identified in patients. In addition, patients displayed impaired activation in a right sub hippocampal region where activity predicted successful associative memory formation for PEK stimuli. Despite the limited sample sizes of this study, these findings suggest that the role prior knowledge in new learning might have been so far overlooked and underestimated in AD patients. Prior knowledge may drive critical differences in the way healthy elderly and early AD patients learn novel associations.

Association between the Val66Met polymorphism (rs6265/G196A) of the BDNF gene and cognitive performance with SSRI use in Arab Alzheimer’s disease patients

Brain derived neutrophic factor (BDNF) is a protein and a member of the neurotrophin family of growth factors, supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. The BDNF gene Val66Met polymorphism (rs6265/G196A) is responsible for BDNF synthesis that impact BDNF function that includes memory and cognition.This study investigated whether the BDNF gene Val66Met polymorphism (rs6265/G196A) is associated with cognitive function changes in both Alzheimer disease (AD) patients and elderly participants. In addition the impact of SSRI use on cognition improvement will be assessed. Healthy young, middle ages (25–59 years old) and elderly (more than 60 years old) participants (140) as well as 40 AD patients of whom are both of Saudi Arabian origin were recruited. The genotyping for the association study was performed by real-time PCR using Taqman chemistry in the ABI Prism 7900HT Sequence Detection System. Both Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) were used to assess cognitive function of healthy and AD participants, respectively.The findings showed that the BDNF Val66Met genotype distributions and allele frequencies have significant association with cognitive performance in both elderly control group and AD patients. The main findings showed that carriers of GG homozygotes (Val/Val) have superior cognitive performance among AD patients and elderly control subjects. In addition the use of SSRIs in 13 AD patients and 17 elderly participants positively improved cognitive function in elderly (p > 0.001) but not in AD patients (p = 0.1).

Reproducibility of Longitudinal Changes in Cortical Thickness Determined by Surface-Based Morphometry Between Non-Accelerated and Accelerated MR Imaging.

Scan acceleration such as parallel imaging reduces scan time, but shorter scan time may reduce the signal-to-noise ratio and affect image quality. The reproducibility of longitudinal changes in the brain structure between non-accelerated and accelerated imaging by surface-based analysis is unclear. To determine the reproducibility of longitudinal changes in cortical thickness, measured by surface-based morphometry, between non-accelerated and accelerated structural T1 -weighted imaging in the healthy elderly and those with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Retrospective. Fifty healthy elderly subjects (age=73 ± 5 years, 29 females, 21 males), 54 MCI patients (age=71 ± 7 years, 23 females, 31 males), and 8 AD patients (age=78 ± 6 years, 6 females, 2 males). 3 T, magnetization-prepared rapid gradient-echo. Longitudinal changes in cortical thickness estimated by the longitudinal stream in FreeSurfer from 2-year interval data, and visual assessment of image quality by three radiologists. Intraclass correlation coefficient (ICC) and Kruskal-Wallis test. A P value <0.05 was considered significant. Healthy elderly subjects, MCI patients, and AD patients showed different patterns in the ICC maps. For the smoothing of 20 mm full width at half maximum, the mean ICC was 0.45 overall (healthy elderly, 0.33; MCI patients, 0.49; AD patients, 0.31). The within-subject SDs of the symmetrized percent changes were similar between healthy elderly subjects (mean, 1.3%/year) and MCI patients (mean, 1.3%/year) but larger in AD patients (mean, 1.7%/year). Image quality did not significantly differ per group (P=0.18). The results of this study indicate the reproducibility of longitudinal changes in cortical thickness measured by surface-based morphometry between non-accelerated and accelerated imaging, and that the reproducibility varies by disease and region. 3 TECHNICAL EFFICACY: Stage 1.

Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis.

Alzheimer's disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aβ (20 μM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aβ-induced deteriorating effects. ALDH2-induced protection against Aβ-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

Ubiquity of the SARS-CoV-2 receptor ACE2 and upregulation in limbic regions of Alzheimer's disease brain.

The major route of entry for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into human host cells is by means of the angiotensin-converting enzyme-2 (ACE2) transmembrane receptor. This zinc-containing carboxypeptidase and membrane-integral surface receptor is ubiquitous and widely expressed in multiple cell types. Hence SARS-CoV-2, an unusually large RNA virus that causes coronavirus disease 2019 (COVID-19) has the remarkable capacity to invade many different types of human host cells simultaneously. Although COVID-19 is generally considered to be primarily an acute respiratory disease SARS-CoV-2 also targets specific anatomical regions of the central nervous system (CNS). In the normal CNS the highest ACE2 levels of expression are found within the medullary respiratory centers of the brainstem and this, in part, may explain the susceptibility of numerous COVID-19 patients to severe respiratory distress. About ~35% of all COVID-19 patients experience neurological and neuropsychiatric symptoms, and apre-existing diagnosis of Alzheimer's disease (AD) predicts the highest risk of COVID-19 yet identified, with the highest mortality among elderly AD patients. In the current study of multiple anatomical regions of AD brains compared to age-, post-mortem interval- and gender-matched controls (n = 10 regions, n = 32 brains), ACE2 expression was found to be significantly up-regulated in AD in the occipital lobe, temporal lobe neocortex and hippocampal CA1. The temporal lobe and hippocampus of the brain are also targeted by the inflammatory neuropathology that accompanies AD, suggesting asignificant mechanistic overlap between COVID-19 and AD, strongly centered on invasion by the neurotropic SARS-CoV-2 virus via the increased presence of ACE2 receptors in limbic regions of the AD-affected brain.

Impact of Combined Photo-Biomodulation and Aerobic Exercise on Cognitive Function and Quality-of-Life in Elderly Alzheimer Patients with Anemia: A Randomized Clinical Trial.

PurposeFew data are available on the positive impact of photo-biomodulation (PBM) using low-level laser therapy as a complementary treatment for improving the cognitive function and optimizing the hemoglobin (Hb) level and oxygen carrying capacity in anemic elderly patients and consequently improving the quality-of-life. The present study aimed to evaluate a new, safe, and easy therapeutic approach to improve Alzheimer’s disease-related symptoms that interfere with the whole life activities and social interaction of elderly patients.Patients and MethodsIn this placebo-controlled clinical trial, 60 elderly patients suffering from anemia and mild cognitive dysfunction were randomly assigned into two equal groups to receive active or placebo low-level laser in addition to a moderate-intensity aerobic exercise over a 12-week period. Hb level as well as cognitive and functional tests were reassessed for any change after 12 weeks of intervention.ResultsBy the end of this study, both groups showed significant improvements in Hb level, Montreal Cognitive Assessment Scale (MoCa – B basic), Quality-of-Life for Alzheimer’s Disease scale, and Berg Balance scale scores along with significant reduction in body mass index (BMI) and waist–hip ratio (WHR) (P<0.0001). The experimental group which received active low-level laser in addition to moderate-intensity aerobic exercise showed more significant results compared to the control group which received placebo low-level laser in addition to moderate-intensity aerobic exercise in all the measured outcomes (P<0.001).ConclusionCombined low-level laser therapy and moderate-intensity aerobic exercises are more effective in improving the cognitive function and quality-of-life of Alzheimer’s disease patients.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04496778.

Decreased Proteasomal Function Induces Neuronal Loss and Memory Impairment

Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia worldwide. There is considerable evidence of age-related disruption of proteostasis being responsible for the development of AD. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and an age-related decline in its activity has been implicated in age-related pathologies. Although proteasomal dysfunction is assumed to be a key AD hallmark, it remains unclear whether its role in disease onset is causative or secondary. In this study, we demonstrate that mice with proteasomal dysfunction exhibited memory impairment with associated neuronal loss, accumulation of phosphorylated tau, and activation of endoplasmic reticulum (ER) stress-related apoptosis pathways. Impaired proteasomal activity also activated ER stress-related apoptosis pathways in HT-22, a murine hippocampal neuronal cell line. HT-22 cell death, caused by proteasomal inhibition, was prevented by an inhibitor of c-Jun N-terminal kinase, an ER stress-related molecule. Collective evidence suggests that impaired proteasomal activity alters proteostasis, and subsequent ER stress-mediated pathways play pivotal roles in neuronal loss. Because aging decreases proteasomal function, age-related impairment of proteasomes may be involved in the development and progression of AD in elderly patients.

Cerebral amyloid accumulation is associated with distinct structural and functional alterations in the brain of depressed elders with mild cognitive impairment

BackgroundElderly patients with late-life depression (LLD) often report mild cognitive impairment (MCI), so Alzheimer's disease (AD) is hard to identify in these patients. We aimed to identify the structural and functional differences between prodromal AD and LLD-related MCI. MethodsWe performed voxel-based morphometry and functional connectivity (FC) analyses in elderly patients with both LLD and MCI to compare alterations between those with cerebral amyloidopathy and those without. We subdivided patients into subthreshold depression (STD) and major depressive disorder (MDD) groups. Using florbetaben positron emission tomography (PET), we compared volume and connectivity between healthy controls and four STD and MDD groups with or without amyloid deposition(A): STD-MCI-A(+), MDD-MCI-A(+), STD-MCI-A(-), and MDD-MCI-A(-). ResultsSubjects with MDD or amyloid deposition showed greater volume reduction in the left middle temporal gyrus. MDD groups had lower FC than STD groups in the frontal, cortical, and limbic areas. The STD-MCI-A(+) group showed greater FC reduction than the MDD-MCI-A(-) and STD-MCI-A(-) groups, particularly in the hippocampus, parahippocampus, and frontal and temporal cortices. The functional differences associated with amyloid plaques were more evident in the STD group than in the MDD group. LimitationsLimitations include disproportional sex ratios, inability to determine the longitudinal effects of amyloidopathy in large populations. ConclusionsRegional gray matter loss and alterations in brain networks may reflect impairments caused by amyloid deposition and depression. Such changes may facilitate the detection of prodromal AD in elderly patients with both depression and cognitive dysfunction, allowing earlier intervention and more appropriate treatment.

Donepezil decreases heart rate in elderly patients with Alzheimer's disease.

Donepezil is an acetylcholinesterase inhibitor (AChI) that improves cognitive function in Alzheimer's disease (AD) patients. However, AChIs are usually associated with peripheral adverse reactions. Here, we investigated the cardiac outcomes in elderly AD patients treated with donepezil. A total of 82 AD patients (age, 75.47±6.53 years) received 5mg or 10mg donepezil (n=41/group) once daily for 12weeks. Next, we examined the heart rate (HR), cardiac rhythm, and PR, QRS, and QTc intervals. Compared to the 5-mg donepezil-treated group, the HR was slower in the 10-mg donepezil-treated group at the 4th, 8th, and 12th weeks of treatment (p=0.041, 0.026, 0.008, respectively). The PR interval was longer in the 10-mg donepezil-treated group at the 12th week of treatment (p=0.022). Compared to the pretreatment values, the post-treatment HR and PR interval in the 10-mg donepezil-treated group were significantly slower and longer, respectively (p=0.002, p=0.005). Further, the HR was significantly correlated to the donepezil dosage (p=0.014). Similarly, donepezil dosage and treatment interval were significantly correlated (p=0.048). Taken together, our findings suggest that 10mg donepezil decreased the HR of elderly AD patients without inducing severe cardiac outcomes. Therefore, AD patients receiving donepezil should undergo regular cardiovascular monitoring. .

Alzheimer's Disease Diagnosis and Severity Level Detection Based on Electroencephalography Modulation Spectral "Patch" Features.

Over the last two decades, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). Typically, resting-state EEG (rsEEG) signals have been used, and traditional frequency bands (delta, theta, alpha, beta and gamma) have been explored. Recent studies, however, have suggested that non-conventional bands may lead to improved diagnostic performance. In this work, we propose a new type of features derived from the 2-dimensional modulation spectral domain representation of the rsEEG signal in order to characterize the neuromodulatory deficit emergent with AD. The proposed features are computed as the power in specific "patches" or regions of interest in the power modulation spectrogram, which are shown to be highly discriminant of AD severity levels. The proposed features were compared with traditional features used in the rsEEG AD monitoring literature. Results showed the proposed features not only achieving improved performance at discriminating between healthy normal elderly controls (Nold) and AD patients with varying severity levels, but also at monitoring severity levels (i.e., mild AD versus moderate AD). Moreover, the proposed features were shown to outperform traditional rsEEG features. Finally, we validated the biological origin of the proposed features by using source localization and comparing the obtained results with ones reported in the AD literature.

Accuracy of praxis test from Cambridge Cognitive Examination (CAMCOG) for Alzheimer's disease: a cross-sectional study.

Praxis impairment may be one of the first symptoms manifested in dementia, primarily in cortical dementia. The Cambridge Cognitive Examination (CAMCOG) evaluates praxis, but little is known about the accuracy of CAMCOG for diagnosing dementia. The aims here were to investigate the accuracy of praxis and its subitems in CAMCOG (constructive, ideomotor and ideational subitems) for diagnosing Alzheimer's disease (AD) among elderly patients. Cross-sectional study on community-dwelling elderly people. 158 elderly patients were evaluated. CAMCOG, Mini-Mental State Examination and Pfeffer Functional Activities Questionnaire were used. ROC curve analysis was used to establish cutoff points. The total scores for praxis and the constructive subitem presented significant differences (P < 0.0001) between healthy elderly people and AD patients. Stage of dementia (clinical dementia rating, CDR = 0, 1 and 2) showed that total and constructive praxis can be used to classify the stages of dementia (mild and moderate cases), i.e. constructive praxis classified 88% of the patients with mild dementia (P < 0.0001) while total praxis classified 56% with moderate dementia. Comparison of normal controls (NC) and mild dementia cases showed specificity of 71% and sensitivity of 88% (AUC = 0.88; P < 0.0001). Some praxis subtests can have higher predictive diagnostic value for detecting Alzheimer's disease in mild stages (total praxis AUC = 0.858; P < 0.0001; constructive AUC = 0.972; P < 0.0001). Constructive praxis as measured using CAMCOG may contribute towards diagnosing dementia, because occurrence of impairment of praxis may help in recognizing an evolving dementia syndrome.

Klotho at the Edge of Alzheimer's Disease and Senile Depression.

Klotho, encoded by the KL gene, is a single-pass transmembrane protein and a circulating factor that plays a key role in cellular metabolism and body homeostasis and has been associated with age-related diseases. Alterations of this protein seem to influence the development of serotonergic neurons and could play a role in major depression in the elderly. Pretreatment of neurons with Klotho protein can avoid neuronal injury related to the toxic amyloid-β and glutamate, centrally related to the pathogenesis of Alzheimer's disease (AD), in order that Klotho protein could play a neuroprotective role in AD patients. Late-life depression, mild cognitive impairment, and dementia are different nosological entities but share common neurobiological facets and could represent a clinical continuum. Enhancement of Klotho levels in the early stages of the disease could represent a therapeutic strategy to prevent further deterioration and to ameliorate the outcome of elderly AD patients with or without major depression.