Canadian Collaborative Study of Tetrahydroaminoacridine (THA) and Lecithin Treatment of Alzheimer's Disease: Effect on Mood

1989 ◽  
Vol 34 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Stephen Vida ◽  
Louise Gauthier ◽  
Serge Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Period ◽  
Rating Scale ◽  
Acetylcholinesterase Inhibitor ◽  
Collaborative Study ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Significant Degree ◽  
Disability Rating Scale

Several lines of evidence have implicated acetylcholine (ACh) as one of the neurotransmitters found to be decreased in Alzheimer's disease (AD). Various methods of cholinergic augmentation have been attempted, with mixed results. Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor, is currently being investigated at the McGill Centre for Studies in Aging. Preliminary uncontrolled data from a 10-week clinical trial of THA and lecithin, reported elsewhere, suggest a clinically modest but statistically significant beneficial effect on cognition, although problems exist with side effects, particularly gastrointestinal. Since the suggestion by Janowsky in 1972 that cholinergic neurotransmission may exert an inhibitory or depressant effect on mood, the evidence accumulated in the literature has been inconclusive. We undertook to assess several potential pretreatment correlates of depressive symptoms in AD and to monitor the course of these symptoms during the 10 week treatment period, using the Geriatric Depression Scale (GDS) of Brink and Yesavage. Pretreatment GDS scores were found to correlate with degree of overall disability and dementia as measured by the Rapid Disability Rating Scale (RDRS) and the Mini Mental State Examination (MMS), respectively. GDS scores over the treatment period did not change to a statistically significant degree. The meaning of these results is discussed, particularly with reference to the difficulty of diagnosis and measurement of depression in the setting of dementia.

scholarly journals Rivastigmine improves dual-task gait velocity in patients with Alzheimer’s disease

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hideki Shimura ◽  
Aiba Saiko ◽  
Akito Hayashi ◽  
Nobutaka Hattori ◽  
Takao Urabe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dual Task ◽  
Acetylcholinesterase Inhibitor ◽  
Randomized Study ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Gait Velocity ◽  
Open Label ◽  
Single Task

Abstract Background Gait impairments are common in patients with Alzheimer’s disease. Cholinesterase inhibitors are used to treat the symptoms of patients with Alzheimer’s disease, but they have not been shown to reduce the severity of Alzheimer’s disease-related gait disorders. Methods This was a prospective, single-arm, open-label, non-randomized study. The aim of the present study was to determine the effect of the acetylcholinesterase inhibitor rivastigmine on gait in 21 newly diagnosed patients with mild to moderate Alzheimer’s disease. The outcome variables were velocity, stride length, and cadence during single-task and dual-task gait trials. The subjects were also assessed with the Mini-Mental State Examination, Alzheimer’s Disease Cooperative Study Activities of Daily Living, Functional Assessment Staging, and Geriatric Depression Scale. Results After 12 weeks of treatment with rivastigmine, gait velocity was significantly improved in the dual-task gait trials; gait velocity was increased from 40.59 ± 13.59 m/min at baseline to 46.88 ± 12.73 m/min when counting backward from 100 in steps of 7 while walking, and gait velocity was increased from 37.06 ± 15.57 m/min at baseline to 42.03 ± 14.02 m/min when naming animals while walking. In the single-task gait trials, which consisted only of walking at their usual pace or at a fast pace, gait velocity was not increased by rivastigmine administration. Conclusion Our findings indicated that rivastigmine improved gait in subjects with mild to moderate Alzheimer’s disease during dual-task trials. The observed enhancement of dual-task gait might be caused by an improvement of cognitive function rather than motor function. Trial registration UMIN, UMIN000025869. Registered December 16, 2016, https://upload.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000029744

scholarly journals Rivastigmine improves dual-task gait velocity in patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Hideki Shimura ◽  
Saiko Aiba ◽  
Akito Hayashi ◽  
Nobutaka Hattori ◽  
Takao Urabe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dual Task ◽  
Acetylcholinesterase Inhibitor ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Gait Velocity ◽  
Single Task ◽  
Fast Pace ◽  
State Examination

Abstract Background Gait impairments are common in patients with Alzheimer’s disease. Cholinesterase inhibitors are used to treat the symptoms of patients with Alzheimer’s disease, but they have not been shown to reduce Alzheimer’s disease-related gait disorders.Methods The aim of the present study was to determine the effect of the acetylcholinesterase inhibitor rivastigmine on gait in 21 newly diagnosed patients with mild to moderate Alzheimer’s disease. The outcome variables were velocity, stride length, and cadence during single-task and dual-task gait trials. The subjects were also assessed with the Mini-Mental State Examination, Alzheimer’s Disease Cooperative Study Activities of Daily Living, Functional Assessment Staging, and Geriatric Depression Scale.Results After 12 weeks of treatment with rivastigmine, gait velocity was significantly improved in dual-task gait trials; gait velocity was increased from 40.59 ± 13.59 m/min at baseline to 46.88 ± 12.73 m/min when counting backward from 100 in steps of 7 while walking, and gait velocity was increased from 37.06 ± 15.57 m/min at baseline to 42.03 ± 14.02 m/min when naming animals while walking. In the single-task gait trials, which consisted only of walking at their usual pace or at a fast pace, gait velocity was not increased by rivastigmine administration.Conclusion Our findings indicated that rivastigmine improved gait in subjects with mild to moderate Alzheimer’s disease. The observed enhancement of dual-task gait might be caused by an improvement of cognitive function rather than motor function.

scholarly journals Rivastigmine improves dual-task gait velocity in patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Hideki Shimura ◽  
Saiko Aiba ◽  
Akito Hayashi ◽  
Nobutaka Hattori ◽  
Takao Urabe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dual Task ◽  
Acetylcholinesterase Inhibitor ◽  
Randomized Study ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Gait Velocity ◽  
Open Label ◽  
Single Task

Abstract Background Gait impairments are common in patients with Alzheimer’s disease. Cholinesterase inhibitors are used to treat the symptoms of patients with Alzheimer’s disease, but they have not been shown to reduce the severity of Alzheimer’s disease-related gait disorders. Methods This was a prospective, single-arm, open-label, non-randomized study. The aim of the present study was to determine the effect of the acetylcholinesterase inhibitor rivastigmine on gait in 21 newly diagnosed patients with mild to moderate Alzheimer’s disease. The outcome variables were velocity, stride length, and cadence during single-task and dual-task gait trials. The subjects were also assessed with the Mini-Mental State Examination, Alzheimer’s Disease Cooperative Study Activities of Daily Living, Functional Assessment Staging, and Geriatric Depression Scale. Results After 12 weeks of treatment with rivastigmine, gait velocity was significantly improved in the dual-task gait trials; gait velocity was increased from 40.59 ± 13.59 m/min at baseline to 46.88 ± 12.73 m/min when counting backward from 100 in steps of 7 while walking, and gait velocity was increased from 37.06 ± 15.57 m/min at baseline to 42.03 ± 14.02 m/min when naming animals while walking. In the single-task gait trials, which consisted only of walking at their usual pace or at a fast pace, gait velocity was not increased by rivastigmine administration. Conclusion Our findings indicated that rivastigmine improved gait in subjects with mild to moderate Alzheimer’s disease during dual-task trials. The observed enhancement of dual-task gait might be caused by an improvement of cognitive function rather than motor function. Trial registration: UMIN, UMIN000025869. Registered December 16, 2016, https://upload.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000029744

scholarly journals Progress Report on the Canadian Multicentre Trial of Tetrahydroaminoacridine with Lecithin in Alzheimer's Disease

1989 ◽  
Vol 16 (S4) ◽  
pp. 543-546 ◽  
Author(s):  
S. Gauthier ◽  
R. Bouchard ◽  
Y. Bacher ◽  
P. Bailey ◽  
H. Bergman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Fixed Dose ◽  
Symptomatic Therapy ◽  
Muscarinic Agonists ◽  
Double Blind ◽  
Disability Rating Scale ◽  
Functional Autonomy ◽  
Disability Rating

ABSTRACT:Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

scholarly journals Value of Neuropsychological Tests to Identify Patients with Depressive Symptoms on the Alzheimer’s Disease Continuum

2020 ◽  
Vol 78 (2) ◽  
pp. 819-826
Author(s):  
Felix Menne ◽  
Carola Gertrud Schipke ◽  
Arne Klostermann ◽  
Manuel Fuentes-Casañ ◽  
Silka Dawn Freiesleben ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Neuropsychological Tests ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Area Under The Curve ◽  
Csf Biomarkers

Background: Depressive symptoms often co-occur with Alzheimer’s disease (AD) and can impact neuropsychological test results. In early stages of AD, disentangling cognitive impairments due to depression from those due to neurodegeneration often poses a challenge. Objective: We aimed to identify neuropsychological tests able to detect AD-typical pathology while taking into account varying degrees of depressive symptoms. Methods: A battery of neuropsychological tests (CERAD-NP) and the Geriatric Depression Scale (GDS) were assessed, and cerebrospinal fluid (CSF) biomarkers were obtained. After stratifying patients into CSF positive or negative and into low, moderate, or high GDS score groups, sensitivity and specificity and area under the curve (AUC) were calculated for each subtest. Results: 497 participants were included in the analyses. In patients with low GDS scores (≤10), the highest AUC (0.72) was achieved by Mini-Mental State Examination, followed by Constructional Praxis Recall and Wordlist Total Recall (AUC = 0.714, both). In patients with moderate (11–20) and high (≥21) GDS scores, Trail Making Test-B (TMT-B) revealed the highest AUCs with 0.77 and 0.82, respectively. Conclusion: Neuropsychological tests showing AD-typical pathology in participants with low GDS scores are in-line with previous results. In patients with higher GDS scores, TMT-B showed the best discrimination. This indicates the need to focus on executive function rather than on memory task results in depressed patients to explore a risk for AD.

scholarly journals Awareness of the COVID-19 Outbreak and Resultant Depressive Tendencies in Patients with Severe Alzheimer’s Disease

2020 ◽  
Vol 77 (2) ◽  
pp. 539-541
Author(s):  
Akito Tsugawa ◽  
Shu Sakurai ◽  
Yuta Inagawa ◽  
Daisuke Hirose ◽  
Yoshitsugu Kaneko ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Recognition Rate ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Face Mask ◽  
Geriatric Depression ◽  
Severe Dementia ◽  
Scale Scores ◽  
Current Events

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer’s disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: “Do you know COVID-19?” and “Why are you wearing a face mask?”. Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.

scholarly journals Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer’s Disease: A Pilot Study

2018 ◽  
Vol 8 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Carola G. Schipke ◽  
Ann De Vos ◽  
Manuel Fuentes ◽  
Dirk Jacobs ◽  
Eugeen Vanmechelen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Csf Biomarkers ◽  
Postsynaptic Protein ◽  
Depressive Symptom Severity ◽  
Early Alzheimer’S Disease ◽  
T Tau

Background/Aims: Major depressive disorder (MDD) can cooccur with early Alzheimer’s disease (AD) or may cause memory problems independently of AD. Previous studies have suggested that the AD-related cerebrospinal fluid (CSF) biomarkers tau and Aβ(1–42) could help discriminate between early AD and depression unrelated to AD. Moreover, the postsynaptic protein neurogranin and presynaptic BACE1 have increasingly gained attention as potential new AD biomarkers, but they have not yet been investigated concerning depression. Methods: Using ELISAs, we studied CSF neurogranin and BACE1 levels in patients with mild (n = 21) and moderate (n = 19) AD, as well as in MDD patients with (n = 20) and without (n = 20) cognitive deficits. The clinical examinations included analyses of t-tau, Aβ(1–42), and Aβ(1–40), besides neuropsychological tests and cranial magnetic resonance imaging. Depressive symptom severity was assessed using the Geriatric Depression Scale (GDS). Results: Along with classic AD biomarkers, neurogranin and BACE1 CSF levels differed between moderate AD and MDD (p ≤ 0.01). MDD associated with cognitive deficits was distinguished from mild AD through the CSF neurogranin/BACE1 ratio (p < 0.05), which was strongly correlated with GDS scores (ρ = –0.656; p < 0.01). Conclusion: The neurogranin/BACE1 ratio in CSF can distinguish between depression and AD among patients with similar cognitive deficits, along with the classic AD biomarkers. Further longitudinal studies are ongoing to identify which biomarkers have prognostic value.

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