Occurrence Of Mild Cognitive Impairment Research Articles

Reductive Stress: A New Concept in Alzheimer's Disease.

Reactive oxygen species play a physiological role in cell signaling and also a pathological role in diseases, when antioxidant defenses are overwhelmed causing oxidative stress. However, in this review we will focus on reductive stress that may be defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. This may occur in hypoxia and also in several diseases in which a small but persistent generation of oxidants results in a hormetic overexpression of antioxidant enzymes that leads to a reduction in cell compartments. This is the case of Alzheimer's disease. Individuals at high risk of Alzheimer's (because they carry the ApoE4 allele) suffer reductive stress long before the onset of the disease and even before the occurrence of mild cognitive impairment. Reductive stress can also be found in animal models of Alzheimer's disease (APP/PS1 transgenic mice), when their redox state is determined at a young age, i.e. before the onset of the disease. Later in their lives they develop oxidative stress. The importance of understanding the occurrence of reductive stress before any signs or symptoms of Alzheimer's has theoretical and also practical importance as it may be a very early marker of the disease.

Correlation of homocysteine metabolic enzymes gene polymorphism and mild cognitive impairment in the Xinjiang Uygur population.

BackgroundThe aim of this study was to investigate the genetic polymorphisms in the homocysteine (HCY) metabolic enzymes in the Xinjiang Uygur population who have mild cognitive impairment (MCI).Material/MethodsBased on the epidemiological investigation, 129 cases of diagnosed Uygur MCI patients and a matched control group with 131 cases were enrolled for analyzing the association between the polymorphisms in the HCY metabolism related genes (C677T, A1298C, and G1968A polymorphisms in MTHFR, as well as the A2756G polymorphism in MS) and MCI by using the SNaPshot method. We then determined the homocysteine level in patients.ResultsIn Xinjiang Uygur subjects, the A1298C polymorphisms in MTHFR and the A2756G polymorphisms in the MS gene in the MCI group were different from those in the control group. However, the C677T and G1968A polymorphisms in the MTHFR gene in MCI patients were not different from those in the control group. Multivariate logistic regression showed that, in addition to the well-known risk factors, such as low education level, high cholesterol level, high level of low-density lipoprotein, and high homocysteine levels, the A>G mutation in the MS gene at the rs1805087 locus was another independent risk factor for MCI in the Uyghur MCI population. The risk of MCI in G allele carriers was 2.265 times higher than that in matched control individuals (95% CI: 1.205~4.256, P<0.05).ConclusionsThe genetic polymorphism of HCY metabolizing enzymes is correlated to the occurrence of MCI in the Xinjiang Uygur population. The A2756G polymorphism in the MS gene could be an independent risk factor for MCI in the Xinjiang Uygur population.

Configuration-specific immunotherapy targeting cis pThr231-Pro232 tau for Alzheimer disease

Tau pathology is the main pathological characteristic of mild cognitive impairment (MCI) and Alzheimer disease (AD), and tau-based therapeutic strategies have great implications in the prevention of MCI and AD. The phosphorylation of threonine 231 preceding proline 232 (pThr231-Pro232) triggers tau hyperphosphorylation, tau aggregation, and tau pathology. Interestingly, the pThr231-Pro232 motif may be in a cis or trans configuration, but several recent studies have firstly indicated that cis, but not trans, pThr231-Pro232 tau is a striking therapeutic target for MCI and AD. Cis pThr231-Pro232 tau appears firstly in MCI and accumulates exclusively in the development of AD. Moreover, cis pThr231-Pro232 tau has low affinity to microtubules, high resistance to dephosphorylation and degradation, and a potent tendency to aggregate. On the contrary, trans pThr231-Pro232 tau has normal physiological activity in vivo. Fortunately, Pin1 is the only known isomerase that catalyzes pThr231-Pro232 tau from the neurotoxic cis to nontoxic trans configuration, which prevents MCI and AD. Nonetheless, as we have mentioned before, Pin1 is frequently inactivated under abnormal physiological conditions in vivo. Therefore, it is necessary to clear cis pThr231-Pro232 tau by immunotherapy when Pin1 is insufficient, in order to avoid the occurrence of MCI and AD.

SAT0079 Mutual Associations among Musculoskeletal Diseases, Metabolic Syndrome, and Cognitive Impairment: A 3-Year Follow-Up of the ROAD Study

BackgroundThe leading cause of disability requiring support is cardiovascular disease, followed by dementia/cognitive impairment, senility, osteoarthritis (OA), and fall/osteoporotic fracture in Japan. However, no study has clarified the interactions between...

Occurrence and risk factors of mild cognitive impairment in the older Chinese population: a 3‐year follow‐up study

To investigate the occurrence and risk factors of mild cognitive impairment (MCI) and the conversion rates to dementia in Chinese people over 80 years of age. Two hundred and two participants (>80 years old) without dementia were assessed clinically using neuropsychological tests; they were re-assessed at 1, 2, and 3 years. The results revealed that 30.2% of the study population was classified as having MCI at baseline. Multivariate linear regression analysis showed that coronary heart disease, hypertension, and stroke were risk factors of MCI. During the 3 years follow-up, the occurrence of MCI increased, and 21.8% of the participants with MCI progressed to dementia. These results suggest that in the older elderly, prevention and early treatment of cardiovascular and cerebrovascular diseases may be effective in lowering the risk of MCI. MCI is a high risk factor for dementia.

Relationship between plasma total homocysteine and mild cognitive impairment in senile patients with type 2 diabetes

To explore the relationship between fasting plasma level of total homocysteine (tHcy) and mild cognitive impairment in senile patients with type 2 diabetes mellitus. A total of 88 senile type 2 diabetics with mild cognitive impairment treated at our hospital from July 2008 to November 2010 were recruited into the MCI group while 52 senile type 2 diabetics into the DNC group. And the control group was composed of 36 healthy elders. The parameters of tHcy, total glyceride (TG), total cholesterol (TC), low density lipoprotein-C (LDL-C), high density lipoprotein-C (HDL-C), creatinine (Cr), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2 h plasma glucose (2 hPG), fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR), folic acid (FA) and vitamin B(12) (VitB(12)) were detected. The patients had a higher level of tHcy in the MCI group than those in the NCM and control groups [(11.3 ± 1.8) vs (9.8 ± 1.5) and (8.1 ± 1.1) µmol/L; P < 0.01]. ROC curve showed that tHcy level had some value of predicting the occurrence of mild cognitive impairment in senile patients with type 2 diabetes mellitus (AUC 0.825, 95%CI 0.758-0.893, P < 0.01). Logistic regression analysis showed that tHcy, SBP, HbA1c, 2 h PG, FINS, LDL-C, HOMA-IR, FA and VitB(12) [OR value: 3.64, 1.68, 1.10, 1.05, 0.81, 1.42, 0.83, 0.74, 0.86 (P < 0.05 or 0.01)] were independent risk factors of mild cognitive impairment in senile diabetic patients. Such factors as tHcy, SBP, HbA1c, FPG, 2 hPG, FINS, LDL-C, HOMA-IR, FA and VitB(12) induce senile patients with type 2 diabetes mellitus to suffer mild cognitive impairment. But tHcy level may play an important role in senile diabetic patients with mild cognitive impairment.

Prevalence of gender disparities and predictors affecting the occurrence of mild cognitive impairment (MCI)

The aims were to investigate the prevalence of mild cognitive impairment (MCI) within gender disparities in Malaysian older adults, and to determine the predictors of MCI according to gender disparities. A community-based sample of urban, multiethnic dwelling elderly aged 60 years of age and above from Cheras, Kuala Lumpur was recruited. Prevalence of all-type MCI, amnestic-type MCI (am-MCI) and non-amnestic-type MCI (nam-MCI) was assessed using comprehensive neuropsychological batteries. The association between demography, socioeconomic status, lifestyle practices, and nutritional status and health risk factors with MCI were examined. Predictors of MCI occurrence between gender disparities were determined. The prevalence of all-type MCI, am-MCI and nam-MCI was 21.1%, 15.4% and 5.7%, respectively. Binary logistic regression indicated that hypercholesterolemia is the significant predictor for MCI in men after adjustment for age, ethnicity and total years of education. While, in women, MCI was best predicted by married status, without exercise practice, overweight and obesity. These results suggest that approximately one-fifth of the studied elderly people had MCI. Predictors for MCI are totally different between men and women. It is critical to identify those at higher risk for MCI in order to implement preventative measures to delay or reverse this abnormal condition.

The H1 Haplotype of the Tau Gene (MAPT) is Associated with Mild Cognitive Impairment

Mild cognitive impairment is often considered a transitional condition prodromal to Alzheimer's disease. The dissection of genetic risk factors predisposing to mild cognitive impairment is paramount to assess the individual predisposition and reliably evaluate the effectiveness of early therapeutic interventions. We designed a cross-sectional analysis to test whether the occurrence of mild cognitive impairment is influenced by variations of the tau protein gene. The genotypes of seven polymorphisms tagging the major tau haplotypes were assayed on 186 patients with amnestic mild cognitive impairment and 191 unrelated controls. Association study was conducted by logistic regression including APOE genotype and age as covariates. Case-control analysis showed that the common H1 haplotype is significantly overrepresented in patients (OR, 95% CI: 2.31, 1.52-3.51; p<0.001), whereas did not provide positive signals for any of the H1 sub-haplotypes that had been described as associated with Alzheimer inverted exclamation mark s disease. This finding was confirmed when the epsilon4 allele of the APOE gene was taken into account (OR, 95% CI: 2.319, 1.492-3.603; p<0.001). These results firstly suggest that the risk of mild cognitive impairment is influenced by tau protein gene variations and that mild cognitive impairment shares a common genetic background with Alzheimer's disease. They may help elucidating the genetic risk to cognitive decline and designing effective clinical trials.

Dementia, Mild Cognitive Impairment and Quantitative EEG in Patients with Parkinson's Disease

The objective of this study was to evaluate relationships between quantitative EEG (qEEG) changes and cognitive disturbance (mild cognitive impairment or dementia) and the motor disturbance stage in Parkinson's disease (PD). Thirty-two PD patients (age = 67.2 +/- 10.0) and 26 normal subjects (age = 68.4 +/- 4.7) were assessed using a neurological evaluation, modified Hoehn and Yahr (HY) scale for PD, a Portuguese version of the CERAD neuropsychological battery (consortium to establish a registry for Alzheimer's disease) incorporating the Mini-mental Status Examination, Clinical Dementia Rating and an EEG analysis of absolute and relative band amplitude at rest. Four groups were compared: three with PD (7 patients with dementia, 10 with mild cognitive impairment and 15 with no cognitive disturbances) and the control group. The qEEG showed no significant differences between the control group and PD patients without cognitive disturbance. Abnormalities on the qEEG were essentially associated with the occurrence of mild cognitive impairment or dementia in patients with PD. There was an increase in the absolute and relative posterior theta amplitude in the groups with mild cognitive impairment or dementia and of the posterior absolute and relative delta amplitude in the group with dementia This study suggested qEEG as a possible physiological tool in the assessment of cognitive aspects in PD.

Fat intake at midlife and cognitive impairment later in life: a population‐based CAIDE study

To investigate the association of midlife dietary fat intake to cognitive performance, and to the occurrence of clinical mild cognitive impairment (MCI) later in life in a non-demented population. A longitudinal population-based study. Populations of Kuopio and Joensuu, Eastern Finland. Participants of the CAIDE study were derived from random, population-based samples studied at midlife (1972, 1977, 1982 or 1987). After an average follow-up of 21 years, a total of 1449 (72%) individuals aged 65-80 years participated in the re-examination in 1998. Altogether 82 (5.7%) people were diagnosed as having MCI. Dietary information was collected with a structured questionnaire and an interview at midlife. MCI, global cognitive and executive functions, episodic, semantic and prospective memory and psychomotor speed. Abundant saturated fat (SFA) intake from milk products and spreads at midlife was associated with poorer global cognitive function and prospective memory and with an increased risk of MCI (OR 2.36, 95% CI 1.17-4.74) after adjusting for demographic and vascular factors, other fats and ApoE. On the contrary, high intake of polyunsaturated fatty acids (PUFA) was associated with better semantic memory. Also frequent fish consumption was associated with better global cognitive function and semantic memory. Further, higher PUFA-SFA ratio was associated with better psychomotor speed and executive function. Our data suggests that dietary fat intake at midlife affects cognitive performance and occurrence of MCI later in life. The impact of dietary interventions needs to be tested in clinical trials.

Mild cognitive impairment: experience from a memory clinic

Mild cognitive impairment (MCI) is sometimes a transition between normal aging and dementia. We investigated the occurrence of MCI in a population referred to a memory clinic. The criteria used to diagnose the state were similar to those used by Petersen et al. in many previous publications. A clinical evaluation after approximately 3 years was also performed. In a subsample of 43 subjects, we found that, during 1 year, 37% (136/402) of all investigated subjects were patients with MCI. After a mean follow-up time of 3 years, 11% (5/43) showed cognitive improvement, while 53% (23/43) were stable and showed no cognitive decline or improvement. Fifteen out of 42 patients (35%) deteriorated and were diagnosed as demented during the same time. We conclude that MCI is a heterogeneous concept and that the outcome at follow-up is dependent on which population is studied and how MCI has been defined.