scholarly journals Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

2015 ◽  
Vol 9 ◽  
pp. JEN.S24004 ◽  
Author(s):  
Grant Rutherford ◽  
Brian Lithgow ◽  
Zahra Moussavi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Outcome Measures ◽  
Cognitive Assessment ◽  
Secondary Outcome ◽  
Positive Effects ◽  
Second Stage ◽  
Resting Motor Threshold

Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic coil to induce an electric field in brain tissue. As a pilot study, we investigated the effect of rTMS treatment on 10 volunteers with Alzheimer's disease (AD) in a two-stage study. The first stage consisted of a double-blind crossover study with real and sham treatments. Each treatment block consisted of 13 sessions over 4 weeks. During each session, 2000 TMS pulses at 90%-100% of resting motor threshold were applied to dorsolateral prefrontal cortex bilaterally, and the patients were kept cognitively active by object/action naming during the treatment. The second stage was an open-label study, in which the same treatments were performed in 2-week blocks (10 sessions) approximately every 3 months as follow-up treatments on six of the volunteers, who completed the first stage of the study. Primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Alzheimer's Disease Assessment Scale-cognitive subscale. The secondary outcome measures were the Revised Memory and Behavior Checklist as well as our team's custom-designed cognitive assessments. The results showed a noticeably stronger improvement on all assessments during the real treatment as compared to the sham treatment. The changes in MOCA scores as well as our designed cognitive assessment were found to be statistically significant, with particularly strong results in the six volunteers who were in the early stages of the disease. The long-term trends observed in the second stage of the study also showed generally less decline than would be expected for their condition. It appears that rTMS can be an effective tool for improving the cognitive abilities of patients with early to moderate stages of AD. However, the positive effects of rTMS may persist for only up to a few weeks. Specific skills being practiced during rTMS treatment may retain their improvement for longer periods.

scholarly journals [P-151]: Associative and item memory as outcome measures for Alzheimer's disease clinical trials: A pilot study

2005 ◽  
Vol 1 ◽  
pp. S58-S58
Author(s):  
Andrew E. Budson ◽  
Hyemi Chong ◽  
Lisa M. Sardinha ◽  
Sibyl Salisbury ◽  
Dorene M. Rentz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Pilot Study ◽  
Outcome Measures ◽  
Item Memory

scholarly journals Neuromodulation for Apathy in Alzheimer’s Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study

2020 ◽  
Vol 77 (4) ◽  
pp. 1483-1493
Author(s):  
Prasad R. Padala ◽  
Eugenia M. Boozer ◽  
Shelly Y. Lensing ◽  
Christopher M. Parkes ◽  
Cassandra R. Hunter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Primary Objective ◽  
Secondary Outcome ◽  
Rapid Progression ◽  
Double Blind ◽  
Sham Treatment ◽  
State Examination

Background: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer’s disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. Objective: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. Methods: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. Results: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (–10.1 (–15.9 to –4.3); t (16)  = –3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15)  = 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16)  = 3.29; p = 0.005), and CGI-I (–2.56 (–3.5 to –1.6), t (17)  = –5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. Conclusion: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.

A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease

2013 ◽  
Vol 25 (6) ◽  
pp. 919-927 ◽  
Author(s):  
Nathan Herrmann ◽  
Serge Gauthier ◽  
Neli Boneva ◽  
Ole Michael Lemming
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Neuropsychiatric Symptoms ◽  
Primary Outcome Measure ◽  
Community Dwelling ◽  
Secondary Outcome ◽  
Double Blind

ABSTRACTBackground: Agitation and aggression in Alzheimer's disease (AD) are amongst the most serious of neuropsychiatric symptoms, and contribute to poor outcomes and worse quality of life. Previous studies have suggested a benefit for memantine on agitation and aggression, but none have examined its efficacy in community-dwelling patients with significant agitation and aggression at baseline, utilizing these behaviors as a primary outcome measure.Methods: Patients with moderate-to-severe AD with Neuropsychiatric Inventory (NPI) total score ≥13 and NPI agitation/aggression score ≥1 were randomized to placebo or 20-mg memantine in a double-blind, 24-week trial. Co-primary outcome measures were behavior, measured by total NPI score, and cognition, using the Severe Impairment Battery (SIB). Secondary outcome measures included global assessment, function and other measures of behavior. This trial was registered as Clinicaltrials.gov: NCT00857649.Results: A total of 369 patients (average age = 75, average MMSE = 12) were randomized to placebo or memantine. The study was prematurely terminated due to recruitment problems. There were no statistically significant differences between memantine and placebo in mean change from baseline in NPI, SIB, or any of the secondary outcome measures. Behavior improved in both groups (total NPI change scores −3.90 ± 1.24 for memantine and −5.13 ± 1.23 for placebo). Memantine was generally well tolerated and patient retention in both treatment arms was good.Conclusions: The study failed to show the superiority of memantine in this sample of patients with moderate-to-severe AD with significant baseline agitation and aggression. Methodological limitations could have contributed to these results.

scholarly journals Performance of patients with frontotemporal lobar degeneration on artistic tasks: A pilot study

2014 ◽  
Vol 8 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Maria Cristina Anauate ◽  
Valéria Santoro Bahia ◽  
Ricardo Nitrini ◽  
Marcia Radanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Occupational Therapy ◽  
Frontotemporal Lobar Degeneration ◽  
Cognitive Assessment ◽  
Cognitive Skills ◽  
Visual Observation ◽  
Executive Skills ◽  
Visuospatial Perception

ABSTRACT Several studies have addressed visuospatial and executive skills in artistic activities in Frontotemporal Lobar Degeneration (FTLD) and Alzheimer's disease (AD). Objective: To investigate the performance of FTLD patients compared to controls on two artistic tasks. Methods: Four FTLD patients with mean age of 57 (8.7) years and schooling of 12.2 (4.5) years plus 10 controls with mean age of 62.9 (8.6) years and schooling of 12.3 (4.6) years, were assessed using the Lowenstein Occupational Therapy Cognitive Assessment (LOTCA) and by a three-stage artistic protocol including visual observation, copying and collage, based on a Sisley painting. Results: FTLD patients had lower scores than controls on Visuospatial Perception, Copy, Collage, Examiner's Observation, and Total, showing distinct patterns of performance according to FTLD sub-type: semantic PPA, nonfluent PPA and bvFTD. Conclusion: FTLD patients presented impairment in the visuospatial and executive skills required to perform artistic tasks. We demonstrated that the application of the instrument as a complimentary method for assessing cognitive skills in this group of patients is possible. Further studies addressing larger and more homogeneous samples of FTLD patients as well as other dementias are warranted.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

NF-κB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 18 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Chul Ju Hwang ◽  
Dong-Young Choi ◽  
Mi Hee Park ◽  
Jin Tae Hong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Strategies ◽  
Close Correlation ◽  
Specific Protein ◽  
Brain Inflammation ◽  
Cytokines And Chemokines ◽  
Inflammatory Drugs ◽  
Peptide Fibrils

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

2020 ◽  
Vol 18 (10) ◽  
pp. 758-768 ◽  
Author(s):  
Khadga Raj ◽  
Pooja Chawla ◽  
Shamsher Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Syndrome ◽  
Dopamine Synthesis ◽  
Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

Different Morphology of Neuritic Plaques in the Archicortex of Alzheimer’s Disease with Comorbid Synucleinopathy: A Pilot Study

2020 ◽  
Vol 17 ◽  
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Jaromir Kukal ◽  
Radoslav Matej
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Time Course ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Dystrophic Neurites ◽  
Neuritic Plaques ◽  
Structural Differences ◽  
Lewy Body Variant

Background: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer’s disease (AD) and patients with AD in comorbidity with synucleinopathies. Methods: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer’s disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. Results: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. Conclusion: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

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