scholarly journals The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Yulan Fan ◽  
Ying Gao ◽  
Joseph Therriault ◽  
Jing Luo ◽  
Maowen Ba ◽  
...  

Cerebrospinal fluid (CSF) measurements of neurogranin (Ng) have emerged as a promising biomarker for cognitive decline in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The apolipoprotein E ε4 (APOE ε4) allele is by far the most consistent genetic risk factor for AD. However, it is not known whether the pathophysiological roles of Ng in MCI or AD are related to APOEε4. We stratified 250 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN) ε4 negative (CN ε4−), CN ε4 positive (CN ε4+), MCI ε4 negative (MCI ε4−), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4−), and AD ε4 positive (AD ε4+). CSF Ng levels were significantly increased in APOE ε4 carriers compared to APOE ε4 non-carriers with MCI. In addition, CSF Ng identified MCI ε4+ versus CN ε4−, but not MCI ε4− versus CN ε4−. Similarly, CSF Ng negatively correlated with Mini-Mental State Examination (MMSE) scores at baseline in the MCI ε4+ group. Our findings support the use of CSF Ng as a biomarker of synaptic pathology for AD. We propose that the roles of CSF Ng in the pathophysiology of MCI may be related to APOE ε4.

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  

<b><i>Background:</i></b> Apolipoprotein E (<i>APOE</i>) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of <i>APOE</i> ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of <i>APOE</i> ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer’s Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ). <b><i>Methods:</i></b> Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, <i>APOE</i> ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer’s disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of <i>APOE</i> ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ−). <b><i>Results:</i></b> The prevalence of <i>APOE</i> ε4 is higher in EMCI and LMCI than in CN (<i>p</i> &#x3c; 0.001 for both), and in LMCI than in EMCI (<i>p</i> = 0.001). <i>APOE</i> ε4 allele was significantly higher in Aβ+ subjects than in Aβ− subjects (<i>p</i> &#x3c; 0.001). Subjects who had a lower CSF Aβ42 level and were <i>APOE</i> ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. <b><i>Conclusions:</i></b> An <i>APOE</i> ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that <i>APOE</i> ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.


2015 ◽  
Vol 9 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Mirela Ward ◽  
Juliana F. Cecato ◽  
Ivan Aprahamian ◽  
José Eduardo Martinelli

OBJECTIVE: To evaluate apraxia in healthy elderly and in patients diagnosed with Alzheimer's disease (AD) and Mild cognitive impairment (MCI). METHODS: We evaluated 136 subjects with an average age of 75.74 years (minimum 60 years old, maximum 92 years old) and average schooling of 9 years (minimum of 7 and a maximum of 12 years), using the Mini-Mental State examination (MMSE), Cambridge Cognitive Examination (CAMCOG) and the Clock Drawing Test. For the analysis of the presence of apraxia, eight subitems from the CAMCOG were selected: the drawings of the pentagon, spiral, house, clock; and the tasks of putting a piece of paper in an envelope; the correct one hand waiving "Goodbye" movements; paper cutting using scissors; and brushing teeth. RESULTS: Elder controls had an average score of 11.51, compared to MCI (11.13), and AD patients, whose average apraxia test scores were the lowest (10.23). Apraxia scores proved able to differentiate the three groups studied (p=0.001). In addition, a negative correlation was observed between apraxia and MMSE scores. CONCLUSION: We conclude that testing for the presence of apraxia is important in the evaluation of patients with cognitive impairments and may help to differentiate elderly controls, MCI and AD.


2018 ◽  
Vol 31 (04) ◽  
pp. 491-504 ◽  
Author(s):  
Tiago C. C. Pinto ◽  
Leonardo Machado ◽  
Tatiana M. Bulgacov ◽  
Antônio L. Rodrigues-Júnior ◽  
Maria L. G. Costa ◽  
...  

ABSTRACTObjective:To compare the accuracy of Mini-Mental State Examination (MMSE) and of the Montreal Cognitive Assessment (MoCA) in tracking mild cognitive impairment (MCI) and Alzheimer’s Disease (AD).Method:A Systematic review of the PubMed, Bireme, Science Direct, Cochrane Library, and PsycInfo databases was conducted. Using inclusion and exclusion criteria and staring with 1,629 articles, 34 articles were selected. The quality of the selected research was evaluated through the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2).Result:More than 80% of the articles showed MoCA to be superior to MMSE in discriminating between individuals with mild cognitive impairment and no cognitive impairment. The area under the curve varied from 0.71 to 0.99 for MoCA, and 0.43 to 0.94 for MMSE, when evaluating the ability to discriminate MCI in the cognitively healthy elderly individuals, and 0.87 to 0.99 and 0.67 to 0.99, respectively, when evaluating the detection of AD. The AUC mean value for MoCA was significantly larger compared to the MMSE in discriminating MCI from control [0.883 (CI 95% 0.855-0.912) vs MMSE 0.780 (CI 95% 0.740-0.820) p &lt; 0.001].Conclusion:The screening tool MoCA is superior to MMSE in the identification of MCI, and both tests were found to be accurate in the detection of AD.


2015 ◽  
Vol 21 (6) ◽  
pp. 362-362 ◽  
Author(s):  
Ingrid Arevalo-Rodriguez ◽  
Nadja Smailagic ◽  
Marta Roqué i Figuls ◽  
Agustín Ciapponi ◽  
Erick Sanchez-Perez ◽  
...  

2016 ◽  
Vol 42 (1-2) ◽  
pp. 50-57 ◽  
Author(s):  
Ales Bartos ◽  
Miloslava Raisova

Background: There is a lack of normative studies of the Mini-Mental State Examination (MMSE) for comparison with early Alzheimer's disease (AD) according to new diagnostic criteria. Participants and Methods: We administered the MMSE to normal elderly Czechs and to patients with mild cognitive impairment (MCI) and mild dementia due to AD according to NIA-AA criteria. Results: We established percentile- and standard deviation-based norms for the MMSE from 650 normal seniors (age 69 ± 8 years, education 14 ± 3 years, MMSE score 28 ± 2 points) stratified by education and age. Dementia patients scored significantly lower than the MCI patients and both groups (110 early AD patients) had significantly lower MMSE scores than the normal seniors (22 ± 5 or 25 ± 3 vs. 28 ± 2 points) (p < 0.01). The optimal cutoff was ≤27 points with sensitivity of 86% and specificity of 79% for early detection of AD patients. Conclusion: We provided MMSE norms, several cutoffs, and higher cutoff scores for early AD using recent guidelines.


Sign in / Sign up

Export Citation Format

Share Document