An Observational Clinical Study of the Efficacy and Tolerability of Donepezil in the Treatment of Alzheimer’s Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 189-198 ◽  
Author(s):  
Klaus Hager ◽  
Pasquale Calabrese ◽  
Lutz Frölich ◽  
Claus Göbel ◽  
Frank M. Berger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study

scholarly journals A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer’s disease

2021 ◽  
Author(s):  
Hyeonseok Jeong ◽  
Jooyeon Jamie Im ◽  
Jong-Sik Park ◽  
Seung-Hee Na ◽  
Wonhye Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study ◽  
Focused Ultrasound ◽  
Low Intensity ◽  
Pilot Clinical Study ◽  
Transcranial Focused Ultrasound

scholarly journals O4-02-04: EXPLORING GUT MICROBIOTA AS A SOURCE OF POTENTIAL BIOMARKERS: INITIAL RESULTS FROM THE ANAVEX® 2-73 ALZHEIMER'S DISEASE CLINICAL STUDY

2019 ◽  
Vol 15 ◽  
pp. P1232-P1233
Author(s):  
Frédéric Parmentier ◽  
Adrien Etcheto ◽  
Christopher Missling ◽  
Coralie Williams ◽  
Mohammad Afshar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study ◽  
Gut Microbiota ◽  
Initial Results ◽  
Potential Biomarkers

P2-541: A NON-PHARMACOLOGIC CLINICAL STUDY OF NURSING HOME RESIDENTS WITH ALZHEIMER'S DISEASE AND DEMENTIA USING TIMESLIPS

2006 ◽  
Vol 14 (7S_Part_17) ◽  
pp. P944-P944
Author(s):  
George P. Sillup ◽  
Eileen L. Sullivan ◽  
Ronald K. Klimberg ◽  
Lisa Slater ◽  
Roberto Muniz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nursing Home ◽  
Clinical Study ◽  
Nursing Home Residents

scholarly journals Frequency of preclinical Alzheimer’s disease in Japanese clinical study settings: A meta‐analysis

2021 ◽  
Vol 17 (S10) ◽  
Author(s):  
Kenichiro Sato ◽  
Yoshiki Niimi ◽  
Ryoko Ihara ◽  
Kazushi Suzuki ◽  
Atsushi Iwata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study ◽  
Meta Analysis ◽  
Preclinical Alzheimer’S Disease

scholarly journals Gait Disturbance in Alzheimer's Disease: A Clinical Study

1996 ◽  
Vol 25 (4) ◽  
pp. 313-316 ◽  
Author(s):  
S. T. O'KEEFFE ◽  
H. KAZEEM ◽  
R. M. PHILPOTT ◽  
J. R. PLAYFER ◽  
M. GOSNEY ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study ◽  
Gait Disturbance

scholarly journals REVERSIBLE AND SPECIES-SPECIFIC DEPIGMENTATION EFFECTS OF AZD3293, A BACE INHIBITOR FOR THE TREATMENT OF ALZHEIMER’S DISEASE, ARE RELATED TO BACE2 INHIBITION AND CONFINED TO EPIDERMIS AND HAIR

2016 ◽  
pp. 1-17
Author(s):  
G. Cebers ◽  
T. Lejeune ◽  
B. Attalla ◽  
M. Soderberg ◽  
R.C. Alexander ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Study ◽  
Multiple Dose ◽  
In Vitro Studies ◽  
Beagle Dogs ◽  
Skin Biopsies ◽  
Long Evans ◽  
Dose Levels

Background: AZD3293 (also known as LY3314814) is a novel, potent, non-selective BACE1/BACE2 inhibitor currently in Phase 3 clinical development for the treatment of Alzheimer’s disease. Objectives: The purpose of these studies was to characterize the effects, putative mechanism, and reversibility of hypopigmentation following treatment with AZD3293 in pigmented Long-Evans rats, Beagle dogs, human cell cultures, and humans. Design: Nonclinical studies were conducted in Long-Evans pigmented rats, and both young and older Beagle dogs using a variety of oral dose levels of AZD3293 or AZD3839 (BACE inhibition reference compound; used in older dogs only) for dosing durations of 13 to 26 weeks. In vitro studies of normal human epidermal melanocytes and reconstituted human epidermis were also conducted. Skin biopsy data from a multiple-dose Phase 1 clinical study of AZD3293 (NCT01795339) are also reported. Setting: Nonclinical in vivo and in vitro studies were conducted in laboratory settings in the US, Canada, and France; the multiple dose clinical study was conducted in a specialized inpatient setting in the US. Participants: Beagle dogs: 13-week study N=36 young (8-10 mo) animals; 39-week study N=64 young animals; and a second 13-week study N=32 older (30-32 mo) animals. Long-Evans rats: N=68 animals. Multiple-dose clinical study: only data for subjects enrolled in Part 2 of this study are included in this report (N=16). Interventions: AZD3293 was the primary intervention used in these studies. AZD3839, a relatively BACE1-selective reference inhibitor compound was used in one group in the 13 week study in older Beagle dogs and one in vitro assessment. Finally, AZ1340, another relatively BACE1-selective reference inhibitor compound was used only in one in vitro assessment. Measurements: Measurements for the nonclinical studies in dogs and rats included macroscopic observation and assessment of skin biopsies via histopathology, immunochemistry, and electron microscopy. Measurements for the in vitro studies included melanocyte premelanosome protein (PMEL) processing, cytotoxicity, melanin synthesis, Pmel17 labeling, and melanocyte dendricity. Measurements in the clinical study included scoring of melanin content in skin biopsies taken before and after dosing with AZD3293 over 14 days at dose levels up to 150 mg. Results: Depigmentation in rats and dogs was limited to skin, hair, and mucosa with no effects on other pigmented tissues. At a cellular level depigmentation was observed within a week of treatment, whereas the appearance of depigmentation in skin and hair did not become apparent until, at earliest, 4 weeks of treatment. The depigmentation effects were reversible, not associated with degenerative or inflammatory changes, and were dose- and species-dependent in severity. Full recovery of melanization was observed at the microscopic (cellular) level and at least partial recovery was seen in the macroscopic appearance of animals by the end of the 12-week recovery period in both rats and dogs. Interestingly, no changes in melanin production or melanocyte morphology were seen in human primary melanocytes or reconstituted human epidermis in vitro. Finally, there were no changes in melanization level in skin biopsies following 12 days of daily AZD3293 treatment at doses of AZD3293 up to 150 mg/day in human subjects. Conclusions: AZD3293, a novel, potent, non-selective BACE1/BACE2 inhibitor is in development as a potentially disease-modifying treatment for Alzheimer’s disease. Chronic nonclinical studies in Beagle dogs and pigmented rats showed macroscopic and microscopic hypopigmentation effects of AZD3293 that were limited to skin, hair, and mucosa. These effects were shown to be reversible in both species. Analysis of data from nonclinical and in vitro studies suggests that hypopigmentation is caused by BACE2 inhibition resulting in accumulation of a premelanosome protein fragment, which interrupts the normal production of melanin. No macroscopic or microscopic reports of hypopigmentation were observed in a Phase 1 clinical study following 13 doses of AZD3293 over 14 days at dose levels up to 150 mg/day. These data suggest that hypopigmentation is species-specific and humans appear to be least sensitive to the depigmentation effect caused by BACE2 inhibition.

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