Donepezil in the treatment of Alzheimer's disease: Results from the first year of a study in clinical practice in the UK

1999 ◽  
Vol 9 ◽  
pp. 327-328
Author(s):  
H.P. Matthews ◽  
J. Korbey ◽  
D.G. Wilkinson ◽  
J. Rowden
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
First Year ◽  
The Uk

scholarly journals Breast Cancer, Alzheimer’s Disease, and APOE4 Allele in the UK Biobank Cohort

2021 ◽  
Vol 5 (1) ◽  
pp. 49-53
Author(s):  
Steven Lehrer ◽  
Peter H. Rheinstein
Keyword(s):  
Breast Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apoe Genotype ◽  
Uk Biobank ◽  
Breast Cancer Patients ◽  
Apoe4 Allele ◽  
Significant Difference ◽  
The Uk ◽  
Cognitive Problems

Background: Cognitive problems are common in breast cancer patients. The apolipoprotein E4 (APOE4) gene, a risk factor for Alzheimer’s disease (AD), may be associated with cancer-related cognitive decline. Objective: To further evaluate the effects of the APOE4 allele, we studied a cohort of patients from the UK Biobank (UKB) who had breast cancer; some also had AD. Methods: Our analysis included all subjects with invasive breast cancer. Single nucleotide polymorphism (SNP) data for rs 429358 and rs 7412 was used to determine APOE genotypes. Cognitive function as numeric memory was assessed with an online test (UKB data field 20240). Results: We analyzed data from 2,876 women with breast cancer. Of the breast cancer subjects, 585 (20%) carried the APOE4 allele. Numeric memory scores were significantly lower in APOE4 carriers and APOE4 homozygotes than non-carriers (p = 0.046). 34 breast cancer subjects (1.1%) had AD. There was no significant difference in survival among genotypes ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4. Conclusion: UKB data suggest that cognitive problems in women with breast cancer are, for the most part, mild, compared with other sequelae of the disease. AD, the worst cognitive problem, is relatively rare (1.1%) and, when it occurs, APOE genotype has little impact on survival.

scholarly journals Motor-Skill Learning in Alzheimer’s Disease: A Review with an Eye to the Clinical Practice

2007 ◽  
Vol 17 (3) ◽  
pp. 203-212 ◽  
Author(s):  
Ilse A. D. A. van Halteren-van Tilborg ◽  
Erik J. A. Scherder ◽  
Wouter Hulstijn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Motor Skill ◽  
Skill Learning ◽  
Motor Skill Learning

scholarly journals Assessing the Progression of Alzheimer’s Disease in Real-World Settings in Three European Countries

2021 ◽  
Vol 80 (2) ◽  
pp. 749-759
Author(s):  
Albert Lladó ◽  
Lutz Froelich ◽  
Rezaul K. Khandker ◽  
Montserrat Roset ◽  
Christopher M. Black ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mixed Model ◽  
Primary Objective ◽  
Community Dwelling ◽  
Behavioral Changes ◽  
The Uk ◽  
State Examination ◽  
Study Inclusion

Background: There exists considerable variation in disease progression rates among patients with Alzheimer’s disease (AD). Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. Results: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, ‘not reached’) years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. Conclusion: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.

scholarly journals Knowledge and perceptions of Alzheimer’s disease in three ethnic groups of younger adults in the United Kingdom

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aysegul Humeyra Kafadar ◽  
Christine Barrett ◽  
Kei Long Cheung
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethnic Groups ◽  
Cultural Beliefs ◽  
Education Level ◽  
Age Group ◽  
Knowledge Level ◽  
Younger Adults ◽  
Gender Education ◽  
The Uk

Abstract Background Alzheimer’s disease (AD) is a global public health problem with an ageing population. Knowledge is essential to promote early awareness, diagnosis and treatment of AD symptoms. AD knowledge is influenced by many cultural factors including cultural beliefs, attitudes and language barriers. This study aims: (1) to define AD knowledge level and perceptions amongst adults between 18 and 49 years of age in the UK; (2) to compare knowledge and perceptions of AD among three main ethnic groups (Asian, Blacks, and Whites); and (3) to assess potential associations of age, gender, education level, affinity with older people (65 or over), family history and caregiving history with AD knowledge. Methods Data was collected from 186 participants as a convenience sample of younger adults of three different ethnicities (16.1% Asian, 16.7% Black, 67.2% White), living in the UK, recruited via an online research platform. The majority of the participants were in the 18–34 years age group (87.6%). Demographic characteristics of participants and AD knowledge correlation were assessed by the 30-item Alzheimer’s Disease Knowledge Scale (ADKS), comprising 7 content domains. ANOVA/ANCOVA were used to assess differences in AD knowledge by ethnicity, gender, education level, age and affinity with dementia and Alzheimer’s patients. Results For AD general knowledge across all respondents only 45.0% answers were correct. No significant differences were found for the total ADKS score between ethnicities in this younger age group, who did not differ in education level. However, there were significant knowledge differences for the ADKS symptom domain score even after controlling for other demographics variables such as gender, education level (p = 0.005). White respondents were more likely to know about AD symptoms than their Black counterparts (p = 0.026). Conclusion The study’s findings suggest that the AD knowledge level is not adequate for all ethnic groups. Meanwhile, significant differences were observed in symptoms, between ethnic groups, and therefore, differ in their needs regards health communication. The study contributes to an understanding of ethnicity differences in AD knowledge amongst adults from 18 to 49 years of age in the UK and may also provide input into an intervention plan for different ethnicities’ information needs.

scholarly journals Genetic overlap between Alzheimer’s disease and depression mapped onto the brain

2021 ◽  
Author(s):  
Jennifer Monereo Sánchez ◽  
Miranda T. Schram ◽  
Oleksandr Frei ◽  
Kevin O’Connell ◽  
Alexey A. Shadrin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Brain Mri ◽  
Genetic Correlations ◽  
Gaussian Mixture ◽  
Brain Morphology ◽  
Uk Biobank ◽  
Genetic Overlap ◽  
The Uk

ABSTRACTBackgroundAlzheimer’s disease (AD) and depression are debilitating brain disorders that are often comorbid. Shared brain mechanisms have been implicated, yet findings are inconsistent, reflecting the complexity of the underlying pathophysiology. As both disorders are (partly) heritable, characterizing their genetic overlap may provide etiological clues. While previous studies have indicated negligible genetic correlations, this study aims to expose the genetic overlap that may remain hidden due to mixed directions of effects.MethodsWe applied Gaussian mixture modelling, through MiXeR, and conjunctional false discovery rate (cFDR) analysis, through pleioFDR, to genome-wide association study (GWAS) summary statistics of AD (n=79,145) and depression (n=450,619). The effects of identified overlapping loci on AD and depression were tested in 403,029 participants of the UK Biobank (mean age 57.21 52.0% female), and mapped onto brain morphology in 30,699 individuals with brain MRI data.ResultsMiXer estimated 98 causal genetic variants overlapping between the two disorders, with 0.44 concordant directions of effects. Through pleioFDR, we identified a SNP in the TMEM106B gene, which was significantly associated with AD (B=-0.002, p=9.1×10−4) and depression (B=0.007, p=3.2×10−9) in the UK Biobank. This SNP was also associated with several regions of the corpus callosum volume anterior (B>0.024, p<8.6×10−4), third ventricle volume ventricle (B=-0.025, p=5.0×10−6), and inferior temporal gyrus surface area (B=0.017, p=5.3×10−4).DiscussionOur results indicate there is substantial genetic overlap, with mixed directions of effects, between AD and depression. These findings illustrate the value of biostatistical tools that capture such overlap, providing insight into the genetic architectures of these disorders.

Planimetry of the medial temporal lobe: a feasible method for supporting the diagnosis of Alzheimer’s disease in clinical practice

10.3823/355 ◽  
2015 ◽  
Author(s):  
Manuel Menéndez González ◽  
Aníbal Fernández Oliveira ◽  
Francisco Conejo Bayón ◽  
Jesús Maese ◽  
Tamara Mesas Uzal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Feasible Method

Cognitive Assessment of Alzheimer’s Disease and Dementias in Clinical Practice

2019 ◽  
Vol 80 (4) ◽  
Author(s):  
Lynn Shaughnessy ◽  
Simon Sheard ◽  
Danielle Goldfarb ◽  
Alireza Atri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Cognitive Assessment

Simulating the Effects of Common Comedications and Genotypes on Alzheimer’s Cognitive Trajectory Using a Quantitative Systems Pharmacology Approach

2020 ◽  
Vol 78 (1) ◽  
pp. 413-424
Author(s):  
Hugo Geerts ◽  
Athan Spiros
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Second Generation ◽  
Standard Of Care ◽  
Systems Pharmacology ◽  
Quantitative Systems Pharmacology ◽  
Pharmacodynamic Interactions ◽  
Cognitive Trajectory

Background: Many Alzheimer’s disease patients in clinical practice are on polypharmacy for treatment of comorbidities. Objective: While pharmacokinetic interactions between drugs have been relatively well established with corresponding treatment guidelines, many medications and common genotype variants also affect central brain circuits involved in cognitive trajectory, leading to complex pharmacodynamic interactions and a large variability in clinical trials. Methods: We applied a mechanism-based and ADAS-Cog calibrated Quantitative Systems Pharmacology biophysical model of neuronal circuits relevant for cognition in Alzheimer’s disease, to standard-of-care cholinergic therapy with COMTVal158Met, 5-HTTLPR rs25531, and APOE genotypes and with benzodiazepines, antidepressants, and antipsychotics, all together 9,585 combinations. Results: The model predicts a variability of up to 14 points on ADAS-Cog at baseline (COMTVV 5-HTTLPRss APOE 4/4 combination is worst) and a four-fold range for the rate of progression. The progression rate is inversely proportional to baseline ADAS-Cog. Antidepressants, benzodiazepines, first-generation more than second generation, and most antipsychotics with the exception of aripiprazole worsen the outcome when added to standard-of-care in mild cases. Low dose second-generation benzodiazepines revert the negative effects of risperidone and olanzapine, but only in mild stages. Non APOE4 carriers with a COMTMM and 5HTTLPRLL are predicted to have the best cognitive performance at baseline but deteriorate somewhat faster over time. However, this effect is significantly modulated by comedications. Conclusion: Once these simulations are validated, the platform can in principle provide optimal treatment guidance in clinical practice at an individual patient level, identify negative pharmacodynamic interactions with novel targets and address protocol amendments in clinical trials.

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