Analysis of C9orf72 Intermediate Alleles in a Retrospective Cohort of Neurological Patients: Risk Factors for Alzheimer’s Disease?

2021 ◽  
pp. 1-7
Author(s):  
Maria Serpente ◽  
Chiara Fenoglio ◽  
Andrea Arighi ◽  
Giorgio G. Fumagalli ◽  
Marina Arcaro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pcr Amplification ◽  
Secondary Memory ◽  
Repeat Units ◽  
Neurological Patients ◽  
Clinical Diagnoses ◽  
Long Term Follow Up ◽  
Clinically Significant ◽  
Intermediate Alleles

Background: C9orf72 hexanucleotide GGGGCC (G4C2) large repeat expansions within the first intron of the gene are a major cause of familial frontotemporal dementia, but also of apparently sporadic cases. Alleles with >  30 repeats are often considered pathogenic, but the repeat length threshold is still undefined. It is also unclear if C9orf72 intermediate alleles (9–30 repeats) have clinically significant effects. Objectives: We correlated the presence of C9orf72 intermediate alleles with clinical diagnoses in a perspective cohort referred to a secondary memory clinic. Methods: All samples were genotyped with AmplideXPCR/CE C9ORF72 Kit (Asuragen, Inc), an optimized C9orf72 PCR amplification reagent. Results: We showed that in patients with Alzheimer’s disease (AD) the frequency of the intermediate repeat allele was significantly increased versus controls (34/54, 63%AD versus 16/39, 41%CTRLs,  *p = 0.01, OR 2.91 CI 95%1.230–6.077), whereas no significant differences (p >  0.05) were observed when comparing all other dementias with non-demented individuals. Conclusion: Our findings suggest that C9orf72 intermediate repeat units may represent a genetic risk factor, contributing to the occurrence of AD. Nevertheless, further longitudinal studies, including larger cohort of subjects with intermediate alleles with long-term follow-up, would be needed to confirm these results.

scholarly journals Plasma P-tau 181, P-tau 217 and Other Blood-Based Alzheimer's Disease Biomarkers in a Multi-Ethnic, Community Study

2020 ◽  
Author(s):  
Adam M. Brickman ◽  
Jennifer J Manly ◽  
Lawrence Honig ◽  
Danurys Sanchez ◽  
Dolly Reyes-Dumeyer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethnic Community ◽  
Community Study ◽  
Community Studies ◽  
Operating Characteristics ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Diagnoses ◽  
Washington Heights

Introduction. Blood-based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights, Inwood, Columbia Aging Project (WHICAP), a multi-ethnic community study of aging and dementia. Methods. We measured plasma Aβ40, Aβ42,T-tau, P-tau181 and P-tau217, and neurofilament light chain (NfL) in 113 autopsied participants, (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD. Results. P-tau181, P-tau217 and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased P-tau217 and P-tau181 were associated with subsequent AD diagnosis. Discussion. Blood-based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi-ethnic, community-based studies.

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 Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes

1997 ◽  
Vol 94 (26) ◽  
pp. 14894-14899 ◽  
Author(s):  
M. Hirano ◽  
A. Shtilbans ◽  
R. Mayeux ◽  
M. M. Davidson ◽  
S. DiMauro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pcr Amplification

The planning of appropriate medical and social care in dementia

2011 ◽  
Author(s):  
Marcel GM Olde-Rikkert ◽  
Irena Draskovic ◽  
Myrra Vernooij-Dassen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Reserve ◽  
Social Care ◽  
Evidence Base ◽  
Significant Decline ◽  
Simple Theory ◽  
Innovative Research ◽  
Research Questions ◽  
Clinically Significant

• Alzheimer’s disease is probably caused by multiple disease processes that occur simultaneously, have a long preclinical history, and together cause a clinically significant decline of cognitive reserve• The cognitive reserve theory is an attractive simple theory that may enable clinicians and researcher to formulate innovative research questions, however it still requires an evidence base...

Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort

2009 ◽  
Vol 22 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Christophe Arbus ◽  
Virginie Gardette ◽  
Eric Bui ◽  
Christelle Cantet ◽  
Sandrine Andrieu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Previous History ◽  
Natural Setting ◽  
Antidepressant Prescription ◽  
History Of ◽  
Antidepressant Use ◽  
Clinically Significant ◽  
History Of Depression

ABSTRACTBackground: Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription.Methods: REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI).Results: A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI ≥ 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression.Conclusions: The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

Sensitivity, Specificity, and Positive Predictive Value of Technetium 99-HMPAO SPECT in Discriminating Alzheimer's Disease from other Dementias

1997 ◽  
Vol 10 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Donna L. Masterman ◽  
Mario F. Mendez ◽  
Lynn A. Fairbanks ◽  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
Single Photon ◽  
Photon Emission ◽  
High Sensitivity ◽  
Hmpao Spect ◽  
Clinical Diagnoses ◽  
Sensitivity Specificity

Investigators have reported high sensitivity and specificity values for single photon emission computerized tomography (SPECT) when distinguishing Alzheimer's disease (AD) patients from normal elderly controls or from selected patient groups. The role of SPECT in identifying AD among unselected patients with memory complaints requires investigation. We examined 139 consecutive patients with 99Tc-HMPAO SPECT. NINCDS-ADRDA diagnoses were determined blind to SPECT results, and scans were read and classified by visual inspection blind to clinical diagnoses. Bilateral temporoparietal hypoperfusion (TP) occurred in 75% of probable, 65% of possible, and 45% of unlikely AD patients, yielding a sensitivity of 75% and a specificity of 52% when comparing probable AD versus unlikely AD groups. A positive predictive value of 78% was obtained based on a 69% prevalence of AD in our total clinic population. Patients with false-positive results included a variety of dementing illnesses; all patients with bilateral hypoperfusion had dementia. A pattern of TP on SPECT scans is seen in most patients with AD, but could be found in other dementias as well and cannot be regarded as specific to AD. Reduced TP perfusion discriminated between demented and nondemented individuals. Further strategies for SPECT interpretation that improve diagnostic specificity should be sought.

scholarly journals Depression as a Risk Factor for Alzheimer’s Disease: A Systematic Review of Longitudinal Meta-Analyses

2021 ◽  
Vol 10 (9) ◽  
pp. 1809
Author(s):  
Olalla Sáiz-Vázquez ◽  
Patricia Gracia-García ◽  
Silvia Ubillos-Landa ◽  
Alicia Puente-Martínez ◽  
Silvia Casado-Yusta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Rating Scales ◽  
Rating Scale ◽  
Symptoms Of Depression ◽  
Clinically Significant ◽  
Criteria For Diagnosis ◽  
Meta Analyses ◽  
Clinical Measures

Alzheimer’s disease (AD) is the most frequent cause of dementia, linked to morbidity and mortality among elderly patients. Recently, several clinical studies suggested that depression is a potential risk factor for cognitive decline and AD. A review of meta-analyses was performed, calculating pooled odds ratios to estimate the risk of AD in people with a prior diagnosis (or clinically significant symptoms) of depression. A total of six meta-analyses which represented 28 individual studies were analyzed. A significant association between depression and AD was found (OR = 1.54, 95% CI [1.02–2.31]; p = 0.038). The results showed that heterogeneity across studies was substantial. We found a significant positive effect size for clinical measures of depression, but not for symptomatic rating scales, in the association of depression with risk of AD. The type of rating scale used to assess depression and the cut-off criteria selected also moderated the relationship between depression and AD risk. We found that studies that used clinically significant criteria for diagnosis of depression had more consistent and significant results than studies that used symptomatic scales.

Risperidone in the Treatment of Patients With Alzheimer's Disease With Negative Symptoms

2000 ◽  
Vol 12 (4) ◽  
pp. 527-536 ◽  
Author(s):  
Arnaldo E. Negrón ◽  
William E. Reichman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Negative Symptoms ◽  
Emotional Reactivity ◽  
Rating Scales ◽  
Behavioral Assessment ◽  
Cognitive Status ◽  
Day Range ◽  
Clinically Significant ◽  
Positive And Negative Symptoms

Introduction: Negative symptoms such as diminished initiative, drive, motivation, and emotional reactivity have been described in patients with Alzheimer's disease (AD). The purpose of this study was to retrospectively analyze the efficacy and tolerability of risperidone for the treatment of clinically significant positive and negative symptoms in AD. Methods: We reviewed the charts of 50 community-residing AD patients who had been treated in a specialized university-based dementia management clinic. Clinical data comparing baseline and 12 weeks of treatment were obtained by reviewing a series of rating scales that were recorded as part of a comprehensive behavioral assessment. Results: Reviewed subjects had a mean age of 79.7±6 years and a mean of 12±3.6 years of school. Seventy percent of the subjects were female and the majority was White. The mean dose of risperidone prescribed was 1.3±0.6 mg per day (range from 0.5 mg to 3.0 mg). After 12 weeks of treatment, the severity of positive and negative symptoms was significantly reduced. Importantly, improvement in negative symptoms with the use of risperidone appeared to be independent of a positive treatment effect on positive symptoms. Risperidone had insignificant effects on both cognitive status and the emergence of extrapyramidal symptoms. Conclusion: This retrospective study demonstrates that risperidone appears to be efficacious in the treatment of clinically significant positive and negative symptoms in patients with AD.

scholarly journals Are clinical diagnoses of Alzheimer's disease and other dementias affected by education and self-reported race?

2012 ◽  
Vol 24 (3) ◽  
pp. 531-544 ◽  
Author(s):  
Jeanne A. Teresi ◽  
Ellen Grober ◽  
Joseph P. Eimicke ◽  
Amy R. Ehrlich
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Diagnoses
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