Study On The Neuropsychological Features And Plasma Homocysteine Level Of Mild Cognitive Impairment

BackgroundMild Cognitive Impairment (MCI) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia .For the majority of patients, MCI represents a transitional state between normal aging and mild dementia, usually Alzheimer's disease (AD).Now it becomes a hot area of cognitive research. In recent years, studies shown that in addition to presentations featuring memory impairment, symptoms in other cognitive domains (eg, executive function, language, visuospatial skills and calculation/attention) have been identified. MCI, as an independent diagnosis is still controversial. Studies which comprehensively assess the cognitive functions of patients with MCI are few at home. So far there is no recognized MCI screening scale at home and abroad. Mini-mental state examination(MMSE) is the most commonly used in screening cognitive impairment, but several studies have shown that using a cutoff score 26 the MMSE had a sensitivity of 17% to 24.2% to detect MCI and the specificity was 100%.It can be obviously seen that MMSE as a main screening tool for MCI is not enough . Montreal Cognitive Assessment Scale (MoCA) is designed for screening MCI in patients scoring between 24 and 30 points on the MMSE, but it isn't wildly used at home and without the Chinese version of the norm. There are a few reports about MoCA to detect MCI at home. Recent epidemiological studies have indicated that hyperhomocysteine (HHcy) is an independent risk factor for AD, and numerous studies showed that homocysteine (Hcy) plays a neurotoxic role in vitro. There is no systematic study report about the relationship between the plasma Hcy metabolic abnormalities and MCI at home. We aimed to investigate the neuropsychological characteristics of patients with MCI and comparison with the mild AD; to explore the advantages of MoCA in screening for MCI and provide the basis for its application; to determine the relationship of plasma Hcy, folate and vitaminB12 levels of MCI patients with cognitive function, and provide the basis for early intervention therapy of MCI patients.Materials and methods1. SubjectsThe three groups were recruited from the homes for the aged of Guangzhou and the Second Affiliated Hospital of Guangzhou Medical College during March 2008 to February 2009 hospitalization and outpatient department of neurology. The MCI group consisted of 42 elderly participants. MCI was defined according to the criteria of Petersen .the AD group consisted of 20 patients with a diagnosis of probable AD meeting the NINCDS-ADRDA criteria and clinical dementia rating scale (CDR) was 1. The NC group consisted of 55 healthy elderly without dementia and neurological degenerative disease. These three groups were gender, age, complications matched. Individuals who were drug or alcohol abuse ,long-term use of neuroleptic drugs ,with history of serious head injury, depression, schizophrenia, thyroid disease, anemia, vitamin B12 and folate deficiency, diabetes with serious complications, heart, liver, renal dysfunction were excluded. All the subjects were older than 65y and had no history of taking any drugs affected the level of plasma Hcy with last 30 days.2. Neuropsychological testingThe MMSE and the MoCA were administered to all groups in the same day. all groups completed neuropsychological tests in a week which including RVR, logical memory(LM), associate learning, visual recognition, picture recall, similarity , blocks design test (BD), digit span (DS), activities of daily living scale (ADL), clinical dementia rating (CDR), Hachinski Ischemic Scale (HIS), Auditory Verbal Learning Test(AVLT).3. Collection of blood sample4ml fasting venous blood sample, under general drying tube stored in 4℃refrigerator, was collected from each subjects. In 1 hour centrifugation (3000rpm, 10min), Blood plasma and blood cells were separated and admitted to the upper plasma 0.5ml centrifuge tube installed in 1ml stored at -20℃until analyzed plasma Hcy, folate and vitamin B12 concentration.4. Measurement of plasma Hcy, folate and vitaminB12Plasma Hcy concentrations were assayed by fluorescence polarization immunoassay technology. Plasma concentrations of folate and vitaminB12 were assayed by microparticle enzyme immunoassay.5. Statistical analysisAll data were analyzed by SPSS 11.5 software package.Results1. Neuropsychological scales scores of MCI group, mild AD group and NC groupCompared with NC group, the scores of MCI group in DS, similarity were significant lower (P <0.05 ),and the scores of MMSE total score, MoCA total score, BD , RVR, visual recognition ,picture recall, association learning, LM were significant lower (P <0.01 ), but there was no significant difference in the score of ADL between two groups (P> 0.05). Compared with mild AD group, BD scores were significantly higher in MCI group (P <0.05); MCI group had significantly higher scores in the MMSE total score, MoCA scores, DS(back) similarity ,RVR ,visual recognition, picture recall, association learning, LM and lower ADL scores, the differences were significant between two groups (P <0.01), but there was no significant difference in DS(forward ) in the two groups (P> 0.05).2. Comparison of the MoCA score between MCI group, mild AD group and NC groupFor the MoCA sub-items ,the elderly patients with MCI had significantly lower scores than healthy elderly in naming , sustain attention , sentence repetition task, phonemic fluency, abstract, delay recall and time orientation(P<0.05);there were significant differences in trail making, cube drawing, clock drawing, attention and calculation task between the two groups (P<0.01); there was no significant difference in fixed orientation(P> 0.05). Whereas the difference of sentence repetition task, abstract, fixed orientation in MCI group and mild AD group was significant (P<0.05); the difference of naming, calculation task, delay recall, time orientation in MCI group and mild AD group was significant (P<0.01), but there were no significant difference in trail making, cube drawing, clock drawing, attention, sustain attention, phonemic fluency between the two groups (P> 0.05).3. Comparison of the MMSE score between MCI group, mild AD group and NC groupIn MMSE sub-items, there were only significant differences in calculation /attention and delayed recall between MCI group and NC group(P<0.01), although the rest sub-items of the scale MCI group had lower scores but the difference was no significant between the two groups (P> 0.05 ). Compared with mild AD group, MCI cases achieved better and the difference of fixed orientation, immediate memory, delayed recall, three-step instructions, visuospatial structure was significant between the two groups (P <0.05) and there were significant differences in time orientation and calculation task (P <0.01), but there were no significant difference in naming, sentence repetition task, write a sentence between the two groups (P> 0.05).4. Comparison of the sensitivity and specificity of MoCA and MMSE in detecting MCI in the MCI group and NC groupUsing a cutoff score of 26 , sensitivity for MMSE and MoCA to detect MCI was 45.23% and 95.23% respectively, specificity was 96.36%and 72.72% respectively, false negative rate was 54.76% and 5% respectively, false positive rate was 3.63% and 30% respectively, accuracy was 74.22% and 82.47% respectively, positive predictive value was 90.47% and 72.72% respectively, negative predictive value was 69.73% and 95.23% respectively. MoCA and MMSE total score correlation coefficient is 0.741 (P <0.01), showing significant correlation of the two scales.5. Plasma Hcy, folate and VitaminB12 levels in MCI group, mild AD group and NC groupNC group, MCI group and mild AD group among the three groups followed by increased levels of plasma HCY, and reduced the level of VitaminB12 but the differences weren't significant among the three groups(P> 0.05); folate levels among the three groups had no regularity.6. HHcy and cognitive functionThe prevalence of HHcy in patients with cognitive impairment (MCI and mild AD group)and controls was 53.13% and 27.02%(OR=3.060,95%CI 1.137～8.233,χ~2=4.907,P<0.01)。Conclusions1. MCI patients'memory and other cognitive domains were impaired, such as language, executive function, visual spatial ability, attention /calculation.2. Delay recall and calculation / attention may be the sensitive indicators of early diagnosis of MCI. 3. The MoCA is a brief cognitive screening tool with high sensitivity for detecting MCI .It could comprehensively assessment MCI patients'cognitive functions and can be used for screening MCI patients performing in the normal rang on the MMSE.4. The levels of plasma Hcy in patients with MCI were higher than normal.