Study On Association Between Magnesium And Alzheimer's Disease Cognitive Abnormality And Evaluation Of Neuropsychological Tests In The Diagnosis Of Dementia

Background:Alzheimer's disease (AD) is the most common reason for dementia.β-amyloid plaques depositionand neurofibrillary tangles are core pathological features. Currently, it suggests that synaptic loss and function abnormalities are importmant pathogenesisof AD.Synaptic plasticity of hippocampal neurons is closely related with NMDA receptors.Magnesium ion(Mg2+) can modulate the function of NMDA receptors, and become a key regulator of synaptic plasticity.In vitro,an elevation of magnesium concentration increased synaptic density and plasticity of cultured hippocampal neurons. In intact animals, increasing magnesium intake is effective on improving memory,and prolonged lifespan.Inclinical research,24-hour urinary excretion of magnesium of AD group in low-magnesium loading diet are lower than in the control group, which suggests that AD patients may be magnesium insufficient.Based on expanded sample size, further study is needed toanalyseiflow-magnesium status is associatedwith cognitive impairmentand different cognitive domains.Objective:To explore the relationship between24-hour urinary excretion of magnesium and cognitive impairmentand different cognitive domains.Material and Methods:This study is a case-control study.Subjects are outpatientdementia patients,whose spouse are included into the control group. Peking Union Medical College Hospital leads the study collaboratingwith other five hospitals.A total 136 pair of subjects participated in this study, including 103 pair of AD patients and spouse,33 pair of non-AD patients and spouse.Clinical evaluation, including clinical history, physical examination, cognitive function tests and diet habits assessments are completed. Cognitive function evaluation includes global function(MMSE,MoCA), memory(FOM, UCLA verbal learning test),executive function(RVR),visualspatial function(BD) and attention(DS,DSST,DC).ADAS-Cog and ADSC-ADL are added to evaluate cognitive function and activities of daily life for dementia patients.Subjects were requested to avoid high-magnesium diet in the first three days and then collect 24-hour urine.In the fourth day.diet containing fixed amount of magnesium were provided to the subjects and the second 24-hour urine were collected.Urinary magnesium concentration and urine volume was tested. General linear modelwas performed to analyse relationship betweenlow-magnesium status and cognitive impairment, and different cognitive domains.Results:①After expanded sample size, we still found that under non high-magnesium diet and low-magnesium loading diet,the 24 hour urinary magnesium execretion was significant lower in AD petients than the controls.②Under the status of non-high-magnesium diet and low-magnesium loading diet, with the reduction of urinary excretion of magnesium, score of different cognitive tests became lower. Differences werestatistically significant in global function (MMSE,z-score),memory(FOM,UCLA verbal learning test),executive function (RVR) and visualspatial function(BD) but not statistically significant in attention (DS,DSST,DC).③Using general linear model to analyse relationship betweenlow-magnesium status and cognitive impairment, adjusted for age,sex,education level,family history and renal function, with the reduction of urinary excretion of magnesium, Score of different cognitive tests became lower except for DS,DSST and DC, trend test P value was statistically significant。The trend remained significant. after further adjusted for cerebrovascular risk factors④Under non-high-magnesium diet and low magnesium loading diet, the 24 hour urinary magnesium execretion in non-AD group was not significantly different from control group.⑤In non-AD group, urinary magnesium execretion is not related to cognitive impairment.Conclusion:1.24-hour urinary magnesium execretion was lower in AD petients than the controlsunder non high-magnesium diet and low-magnesium loading diet.2.The 24-hour urinary excretion of magnesium is correlated with cognitive impairment.With the reduction of urinary magnesium excretion, score of different cognitive tests became lower.3.24-hour urinary excretion of magnesium is not related to non-AD or non-AD cognitive impairment. Background:With our increasing knowledge of mechanism, pathology, clinical course of dementia, the criteria of dementia has to be revised at intervals to make accurate and early diagnosis. The established criteria and cognitive tests are not sensitive to ealy Alzheimer disease(AD) or mild cognitive impairment. We used UCLA verbal learning test, digit symbol substitution test, digit cancellation test, maze test and stick test to find whether these tests are more sensitive and specific for dementia diagnosis or not. Additional, by evaluatingcognitive function of post-stroke patients and patients of Parkinson disease(PD), we found that with a cut-off point of 26,MoCA was too sensitive to detect cognitive impairment. We hope to find a proper cut-off point for PD dementia and post-stroke dementia patients, and analysed characteristics of the cognitive impairment of these disease.Objective:To establish domestic norm of UCLA verbal learning test, digit symbol substitution test, digit cancellation test, maze test and stick test, and evaluate the validity of these tests. To evaluate the validity of MoCA as a screening tool for PD dementia and post-stroke dementia.To analyse the differences of neuropsychologic tests among early AD, PD cognitive impairment and post-stroke cognitive impairment.Methods:A total of 356 individuals including 220 healthy elderly controls and 136 dementia patients were tested by UCLA verbal learning test, digit symbol substitution test, digit cancellation test and maze test. A total of 185 individuals aged at 50 or older including 108 healthy elderly controls and 77 dementia patients were tested by stick tests. The average score were given in distributions specific for age, sex and educational level. Using score of the 5th percentile of normal controls by different education levels as a cutoff point, we calculated the sensitivity and specificity. An analysis of agreement using Kappa statistic was performed to determine consistency of diagnosis between different neurophychologic tests.In cognitive evaluation of AD, PD and post-stroke patients,103 AD patients from "magnesium status and Alzheimer disease" study,42 MCI due to AD patients from outpatient clinic; 671 stroke patients from "Cognitive impairment after the first-ever stroke:patient older than 45years in Chinese 12 cities"study; 901 patients from Clinical features of Parkinson disease in Chinese 7 cities" study were included. Complete congnitive tests including but not limited to MMSE, MoCA, FOM,RVR,BD and DS. Using score of the 10th percentile of normal controls of PD and post stroke patient by different education levels as a cutoff point, calculate the sensitivity and specificity. Using frequency to describe the abnormity of different cognitive domains to evaluate the most impaired cognitive domain.Results:1. Education level has significant effect on the result of UCLA verbal learning test, digit symbol substitution test, digit cancellation test and maze test but not on stick test.Age has significant effect on digit symbol substitution test and digit cancellation tests.2. UCLA verbal learning test, digit symbol substitution test and stick test part2 have a good sensitivity and specificity for diagnosis of dementia. UCLA verbal learning test and stick test had a high consistency (kappa>0.8) with diagnosis of AD, and sensitivity is higher than FOM(75.38%),especially delay recall(>90%).UCLA verbal learning test is more sensitive in patients with high education level.3. Digit cancellation test and maze test do not have good consistency with diagnosis of AD. Stick test part1 has ceiling effect and is not sensitive in educated patients.4. Using score of the 10th percentile of normal controls, MoCA has a good sensitivity of 79.15%,and specificity of 87.11%.Sensitivty is much higher then MMSE(56.19%).5. FOM abnormity (28.57%) is of highest frequency in MCI dur to AD patients; while BD abnormity is of highest frequency in PD-MCI and VCI patients(38.54% and 60.87%).The abnormity remains dominant in later stages of the disease regardless of other cognitive domains impairment.Conclusion1. UCLA verbal learning test is more accurate in patients of high education level, while FOM is more accurate in patients of low education level.2. DSST and DC are ideal tool with high sensitivity and specificity for attention impairment.3. Stick test part1 is not sensitive in educated population, but part2 is a sensitive instrument for memory impairment. Stick test is convenient to operate, could be an useful instrument in outpatient clinic. 4. MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting PDD and VaD.5. Impairment in memory is most common in MCI due to AD patients. Impairment of visualspacial function is most common in PD-MCI and PDD patients. Impairment of executive function and visualspacial function is most seen in post-stroke cognitive impairment patients.