scholarly journals Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke

2021 ◽  
pp. 154596832110628
Author(s):  
Steven C. Cramer ◽  
Jill See ◽  
Brent Liu ◽  
Matthew Edwardson ◽  
Ximing Wang ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Cerebral Atrophy ◽  
Stroke Onset ◽  
Carrier Status ◽  
Genetic Associations ◽  
Rehabilitation Therapy ◽  
Post Stroke ◽  
Apoe Ε4 ◽  
Neuroimaging Data ◽  
Wolf Motor Function Test

Objective Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. Methods The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val66met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). Results Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val66met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val66met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). Conclusion Neither the val66met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val66met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer’s disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.

scholarly journals Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults

2021 ◽  
Vol 11 (1) ◽  
pp. 68
Author(s):  
Sara G. Aguilar-Navarro ◽  
Itzel I. Gonzalez-Aparicio ◽  
José Alberto Avila-Funes ◽  
Teresa Juárez-Cedillo ◽  
Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Mild Cognitive Impairment ◽  
Cardiovascular Risk Factors ◽  
Apoe Genotype ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Increased Risk

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

scholarly journals Impact of APOE ε4 genotype on initial cognitive symptoms differs for Alzheimer’s and Lewy body neuropathology

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Aaron Bonner-Jackson ◽  
James B. Leverenz
Keyword(s):  
Lewy Body ◽  
Statistical Significance ◽  
Carrier Status ◽  
Initial Symptom ◽  
Cognitive Symptoms ◽  
Clinical Dementia Rating ◽  
Apoe Ε4 ◽  
Initial Symptoms ◽  
Adjusted Model ◽  
The Impact

Abstract Background APOE ε4 carrier status is known to increase odds of amnestic presentations with Alzheimer’s pathology. It is unknown how APOE ε4 carrier status impacts odds of specific initial cognitive symptoms in the presence of Lewy body pathology. Here we evaluate the impact of APOE ε4 genotype on initial cognitive symptoms among those with Alzheimer’s disease pathology (ADP) and Lewy-related pathology (LRP). Methods A retrospective cohort study of 2288 participants with neuropathology confirmed ADP or LRP in the National Alzheimer’s Coordinating Center database, who had initial cognitive symptoms documented and had a Clinical Dementia Rating-Global (CDR-G) score ≤ 1 (cognitively normal, MCI, or early dementia). Unadjusted and adjusted logistic regression models taking into account age at evaluation, sex, and education examined the relationship between APOE ε4 genotype and initial symptoms (memory, executive, language visuospatial) among ADP with LRP and ADP-LRP groups. Results One thousand three hundred three participants met criteria for ADP alone, 90 for LRP alone, and 895 for co-existing ADP and LRP (ADP-LRP). Younger age increased odds of non-amnestic symptoms across all three groups. In the adjusted model among ADP, APOE ε4 carriers had higher odds of amnestic initial symptoms 1.5 [95% CI, 1.7–2.14, p = 0.003] and lower odds of initial language symptoms 0.67 [95% CI, 0.47–0.96, p = 0.03] than non-carriers. The odds for these two symptoms were not different between ADP and mixed ADP-LRP groups. Female sex and higher education increased odds of initial language symptoms in the ADP group in the adjusted model. In the unadjusted model, APOE ε4 carriers with LRP had a higher odds of visuospatial initial symptoms 21.96 [95% CI, 4.02–110.62, p < 0.0001], while no difference was noted for initial executive/attention symptoms. Among LRP, the odds of APOE ε4 on amnestic symptom was not significant; however, the interaction effect evaluating the difference in odds ratios of amnestic symptom between ADP and LRP groups also did not reach statistical significance. Conclusions The odds of specific initial cognitive symptoms differed between ADP and LRP among APOE ε4 carriers compared to non-carriers. The odds of initial amnestic symptom was higher among ADP APOE ε4 carriers and the odds of visuospatial initial symptom was higher with LRP APOE ε4 carriers. This supports the hypothesis that APOE ε4 differentially impacts initial cognitive symptoms together with underlying neuropathology.

scholarly journals P1-369: Effect of APOE-ε4 carrier status on donepezil response in people with mild-to-moderate Alzheimer's dementia

2013 ◽  
Vol 9 ◽  
pp. P293-P293
Author(s):  
Jeffrey Waring ◽  
Qi Tang ◽  
Weining Robieson ◽  
David King ◽  
Ujjwal Das ◽  
...  
Keyword(s):  
Alzheimer’S Dementia ◽  
Carrier Status ◽  
Alzheimer's Dementia ◽  
Apoe Ε4

scholarly journals Predictors of Pharmaco-Resistance in Patients with Post-Stroke Epilepsy

2021 ◽  
Vol 11 (4) ◽  
pp. 418
Author(s):  
Simona Lattanzi ◽  
Claudia Rinaldi ◽  
Claudia Cagnetti ◽  
Nicoletta Foschi ◽  
Davide Norata ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Intracerebral Hemorrhage ◽  
Stroke Onset ◽  
Study Cohort ◽  
Seizure Freedom ◽  
Clinical Predictors ◽  
Post Stroke ◽  
History Of ◽  
Stroke Type ◽  
Patients With Epilepsy

Objectives: The study aimed to explore the clinical predictors of pharmaco-resistance in patients with post-stroke epilepsy (PSE). Methods: Patients with epilepsy secondary to cerebral infarct or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of pharmaco-resistance defined as the failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication schedules, whether as monotherapies or in combination, to achieve sustained seizure freedom. Results: One-hundred and fifty-nine patients with PSE and a median follow-up of 5 (3–9) years were included. The mean age of the patients at stroke onset was 56.7 (14.9) years, and 104 (65.4%) were males. In the study cohort, 29 participants were pharmaco-resistant. Age at stroke onset [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.93–0.99; p = 0.044], history of intracerebral hemorrhage (OR 2.95, 95% CI 1.06–8.24; p = 0.039), severe stroke (OR 5.43, 95% CI 1.82–16.16; p = 0.002), status epilepticus as initial presentation of PSE (OR 7.90, 1.66–37.55; p = 0.009), and focal to bilateral tonic-clonic seizures (OR 3.19, 95% CI 1.16–8.79; p = 0.025) were independent predictors of treatment refractoriness. Conclusions: Pharmaco-resistance developed in approximately 20% of patients with PSE and was associated with younger age at stroke onset, stroke type and severity, status epilepticus occurrence, and seizure types.

Prediction of post-stroke dementia using NINDS-CSN 5-minute neuropsychology protocol in acute stroke

2017 ◽  
Vol 29 (5) ◽  
pp. 777-784 ◽  
Author(s):  
Jae-Sung Lim ◽  
Mi Sun Oh ◽  
Ju-Hun Lee ◽  
San Jung ◽  
Chulho Kim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Screening Method ◽  
Heart Association ◽  
Risk Groups ◽  
Vascular Cognitive Impairment ◽  
Stroke Onset ◽  
University Hospitals ◽  
Cognitive Domains ◽  
Post Stroke ◽  
Neuropsychological Assessments

ABSTRACTBackground:The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke.Method:We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals. Neuropsychological assessments using the NINDS-CSN 5-minute and 60-minute neuropsychology protocols were administered within two weeks and at 3 months after stroke onset, respectively. PSD was diagnosed with reference to the American Heart Association/American Stroke Association statement, requiring deficits in at least two cognitive domains.Results:Of 620 patients, 512 (82.6%) were feasible for the NINDS-CSN 5-minute protocol within two weeks after stroke. The incidence of PSD was 16.2% in 308 subjects who had completed follow-up at 3 months after stroke onset. The total score of the NINDS-CSN 5-minute protocol differed significantly between those with and without PSD (4.0 ± 2.7, 7.4 ± 2.7, respectively; p < 0.01). A cut-off value of 6/7 showed reasonable discriminative power (sensitivity 0.82, specificity 0.67, AUC 0.74). The NINDS-CSN 5-minute protocol score was a significant predictor for PSD (adjusted odds ratio 6.32, 95% CI 2.65–15.05).Discussion:The NINDS-CSN 5-minute protocol is feasible to evaluate cognitive functions in patients with acute ischemic stroke. It might be a useful screening method for early identification of high-risk groups for PSD.

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