scholarly journals Predictors of Life Expectancy After an Alzheimer’s Disease Diagnosis in a National Multi-Center Autopsy-Confirmed Sample

2019 ◽  
Vol 34 (6) ◽  
pp. 845-845
Author(s):  
J Schaffert ◽  
C LoBue ◽  
C Presley ◽  
L Hynan ◽  
K Wilmoth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Psychiatric Symptoms ◽  
Significant Proportion ◽  
Disease Diagnosis ◽  
Small Sample ◽  
Clinical Diagnoses ◽  
Race Ethnicity ◽  
Small Sample Sizes

Abstract Objective Life expectancy varies between 3-12 years following the diagnosis of Alzheimer’s disease (AD) and is an important clinical question for patients and families. Current literature is limited by relatively small sample sizes and a reliance on clinical diagnoses. This study sought to evaluate predictors of AD life expectancy in a large autopsy-confirmed sample. Methods Baseline data from individuals 50 years and older clinically and neuropathologically diagnosed with AD (N=764) were obtained from the National Alzheimer’s Coordinating Center. Life expectancy was calculated in months from AD diagnosis to death. Nineteen variables (demographic, medical/health, disease severity, and psychiatric) obtained at dementia diagnosis were examined. Variables that showed significant differences in life expectancy using t-tests and Pearson correlations (14 of 19) were then entered into a forward multiple regression. Results Seven predictors in the model explained 27% of the variance in life expectancy (F= 40.7, R-squared= 0.267). Lower MMSE scores (β= 0.339, p < .001), male sex (β= -0.144, p < .001), older age (β= -0.130, p < .001), non-Hispanic Caucasian race/ethnicity (β= 0.115, p < .001), greater impairment on the Functional Activities Questionnaire (β= -0.091, p=.042), abnormal neurological/physical exam (β= -0.083, p=.011), and higher Neuropsychiatric Inventory Questionnaire total scores (β= -0.079, p=.016) predicted shorter life expectancy. Conclusions Global cognitive impairment, sex, age, race/ethnicity, functional impairment, abnormal neurological exam findings, and psychiatric symptoms explain a significant proportion of life expectancy following an AD diagnosis. Future studies should explore the relationship between life expectancy, specific neurological abnormalities, and psychiatric symptoms. These 7 predictors could potentially be used to predict life expectancy in individuals diagnosed with AD.

Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer’s Disease

2022 ◽  
pp. 1-11
Author(s):  
Jeff Schaffert ◽  
Christian LoBue ◽  
Linda S. Hynan ◽  
John Hart ◽  
Heidi Rossetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Functional Impairment ◽  
Neuropsychiatric Symptoms ◽  
Primary Objective ◽  
Cognitive Predictors ◽  
Clinical Diagnoses ◽  
Neurological Exam ◽  
Univariate Analyses

Background: Life expectancy (LE) following Alzheimer’s disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses. Objective: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study. Methods: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer’s Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death. Results: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12. Conclusion: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD.

scholarly journals Psychosis in Alzheimer's Disease in the National Alzheimer's Disease Coordinating Center Uniform Data Set: Clinical Correlates and Association with Apolipoprotein E

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Mary Ann A. DeMichele-Sweet ◽  
Oscar L. Lopez ◽  
Robert A. Sweet
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Small Sample ◽  
Carrier Status ◽  
Data Set ◽  
Allele Number ◽  
Heritable Phenotype ◽  
Small Sample Sizes

Approximately 50% of late-onset Alzheimer's disease (AD) patients develop psychosis (AD+P), a heritable phenotype associated with more rapid cognitive decline. Prior studies conflict regarding whether apolipoprotein E (APOE) ϵ4 alleles are associated with AD+P, possibly due to small sample sizes, inconsistent diagnostic criteria, and different methodologies to assess psychosis. We used the National Alzheimer's Coordinating Center Uniform Data Set to evaluate the largest uniformly characterized sample of AD+P subjects studied to date for the association of APOE ϵ4 genotype, along with other demographic and clinical variables. Greater cognitive impairment and depressive symptoms were associated with AD+P, while the Caucasian race was protective. Neither APOE ϵ4 carrier status nor allele number was associated with psychosis. The AD+P phenotype is not associated with the APOE ϵ4 genotype. AD+P may represent a useful phenotype for the discovery of non-APOE ϵ4 genetic variation contributing to the risk of AD.

Neurostimulation for cognitive enhancement in Alzheimer’s disease (the NICE-AD study): a randomized clinical trial

2021 ◽  
Author(s):  
Emma Gulley ◽  
Joe Verghese ◽  
Helena M Blumen ◽  
Emmeline Ayers ◽  
Cuiling Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Sample ◽  
Double Blind ◽  
Dorsolateral Prefrontal ◽  
Stimulation Period ◽  
Small Sample Sizes ◽  
Functional Neuroplasticity ◽  
At Home

New therapies for symptoms in Alzheimer’s disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. This study has been registered on www.Clinicaltrials.gov - identifier: NCT 04404153 .

Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer’s Disease

2020 ◽  
Vol 17 (5) ◽  
pp. 438-445
Author(s):  
Van Giau Vo ◽  
Jung-Min Pyun ◽  
Eva Bagyinszky ◽  
Seong S.A. An ◽  
Sang Y. Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Early Onset ◽  
Parietal Lobe ◽  
Disease Diagnosis ◽  
Random Coil ◽  
Magnetic Resonance Imaging Scan ◽  
Preclinical Ad ◽  
Early Onset Alzheimer’S Disease

Background: Presenilin 1 (PSEN1) was suggested as the most common causative gene of early onset Alzheimer’s Disease (AD). Methods: Patient who presented progressive memory decline in her 40s was enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. Genetic tests were performed in the patient to evaluate possible mutations using whole exome sequencing. The pathogenic nature of missense mutation and its 3D protein structure prediction were performed by in silico prediction programs. Results: A pathogenic mutation in PSEN1 (NM_000021.3: c.1027T>C p.Ala285Val), which was found in a Korean EOAD patient. Magnetic resonance imaging scan showed mild left temporal lobe atrophy. Hypometabolism appeared through 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) scanning in bilateral temporal and parietal lobe, and 18F-Florbetaben-PET (FBB-PET) showed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and hence presumed preclinical AD. Protein modeling showed that the p.Ala285Val is located in the random coil region and could result in extra stress in this region, resulting in the replacement of an alanine residue with a valine. This prediction was confirmed previous in vitro studies that the p.Trp165Cys resulted in an elevated Aβ42/Aβ40 ratio in both COS-1 and HEK293 cell lines compared that of wild-type control. Conclusion: Together, the clinical characteristics and the effect of the mutation would facilitate our understanding of PSEN1 in AD pathogenesis for the disease diagnosis and treatment. Future in vivo study is needed to evaluate the role of PSEN1 p.Ala285Val mutation in AD progression.

scholarly journals Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 12
Author(s):  
Johanna Michael ◽  
Diana Bessa de Sousa ◽  
Justin Conway ◽  
Erick Gonzalez-Labrada ◽  
Rodolphe Obeid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Significant Proportion ◽  
Preclinical Model ◽  
Dependent Manner ◽  
Promising Alternative ◽  
Model Of Alzheimer’S Disease ◽  
Acute And Chronic Exposure

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

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