The role of working memory and attentional disengagement on inhibitory control: effects of aging and Alzheimer's disease

Patients with Alzheimer''s disease have an impairment of inhibitory control for reasons that are currently unclear. Using an eye-tracking task (the gap-overlap paradigm), we examined whether the uncorrected errors relate to the task of attentional disengagement in preparation for action. Alternatively, the difficulty in correcting for errors may be caused by the working memory representation of the task. A major aim of this study was to distinguish between the effects of healthy aging and neurodegenerative disease on the voluntary control of saccadic eye movements. Using the antisaccade task (AST) and pro-saccade task (PST) with the ‘gap’ and ‘overlap’ procedures, we obtained detailed eye-tracking measures in patients, with 18 patients with probable Alzheimer''s disease, 25 patients with Parkinson''s disease and 17 healthy young and 18 old participants. Uncorrected errors in the AST were selectively increased in Alzheimer''s disease, but not in Parkinson''s disease compared to the control groups. These uncorrected errors were strongly correlated with spatial working memory. There was an increase in the saccade reaction times to targets that were presented simultaneously with the fixation stimulus, compared to the removal of fixation. This ‘gap’ effect (i.e. overlap–gap) saccade reaction time was elevated in the older groups compared to young group, which yielded a strong effect of aging and no specific effect of neurodegenerative disease. Healthy aging, rather than neurodegenerative disease, accounted for the increase in the saccade reaction times to the target that are presented simultaneously with a fixation stimulus. These results suggest that the impairment of inhibitory control in the AST may provide a convenient and putative mark of working memory dysfunction in Alzheimer''s disease.     

Effects of cognitive function and depressive mood on the quality of life in Chinese Alzheimer's disease patients in Hong Kong

Aim: In view of the paucity of data on the quality of life (QOL) in Chinese Alzheimer's disease (AD) patients, we investigated the effects of cognitive function and depressive mood on QOL among our Chinese AD patients in Hong Kong, using the Cantonese Chinese version of Quality of Life in Alzheimer's disease (QOL‐AD). Methods: This was a cross‐sectional study. The Cantonese Chinese version of QOL‐AD was adapted from the Mandarin Chinese and English versions of QOL‐AD, and was administered to 111 AD patients and their caregivers. Results: The Cantonese Chinese version of QOL‐AD showed good internal consistency, test–retest and inter‐rater reliability. The patients' and caregivers' reports of QOL‐AD were moderately correlated (r = 0.516, P < 0.001). Both QOL‐AD scores from patient and caregiver reports varied significantly in relation to the severity of cognitive impairment, being lowest in the subgroup with Mini‐Mental State Examination scores of 10 or less. The mean QOL‐AD scores from both patient and caregiver reports were also significantly lower in the depressed (Geriatric Depression Scale [GDS] scores ≥15) than non‐depressed groups (GDS scores ≤15) (QOL‐AD patient report 23.8 and 34.2, respectively, P < 0.001, Student's t‐test; QOL‐AD caregiver report 28.9 and 31.0, respectively, P < 0.05, Student's t‐test). General linear model analyses showed that only the MMSE and GDS scores were independent significant factors associated with the patient but not the caregiver reports of the QOL‐AD. Conclusion: Among Chinese AD patients in Hong Kong, depressive mood and low MMSE score adversely affect the QOL‐AD from the patient but not the caregiver perspectives. Geriatr Gerontol Int 2011; 11: 69–76.     

Vascular risk factors and progression in Alzheimer's disease

Aim: To determine whether vascular risk factors such as hypertension, diabetes and hypercholesterolemia affect the progression of Alzheimer's disease (AD). Methods: We followed up 150 consecutive outpatients with probable AD for 24–60 months. Severity of cognitive impairment was assessed using the Mini‐Mental State Examination (MMSE). We investigated the influence of vascular risk factors and other demographic and clinical conditions (including age, sex, education, initial MMSE score and follow‐up time) on annual MMSE score changes. Results: Multiple regression analysis revealed that age, education and hypertension were significant variables associated with annual MMSE score changes. Younger, more educated patients with hypertension showed greater decline in annual MMSE scores. There were no significant correlations of annual MMSE score changes with other vascular factors or demographics, including sex, initial MMSE score, diabetes or hypercholesterolemia. Conclusion: Younger, more educated patients are more likely to have faster cognitive decline. In addition, hypertension may also be associated with a greater rate of disease progression. Our results suggest the importance of prevention and treatment for hypertension in patients with AD. Geriatr Gerontol Int 2011; 11: 211–214 .     

Pathways to Alzheimer's disease

Recent trials of anti‐amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low‐risk and rare high‐risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti‐amyloid therapies should be initiated early in the disease process.     

Lipids' peroxidation markers in Alzheimer's disease and vascular dementia

Aim: Although a large body of evidence supports a role of oxidative stress in the etiopathogenesis of dementia, there is still a substantial lack of data regarding the biomarkers of oxidative stress characteristic of Alzheimer's disease (AD) as opposed to different types of dementia. In this study, the level of various oxidative stress parameters were measured in AD, vascular dementia (VaD), and age‐ and sex‐matched control patients. The AD and VaD patients all had similar levels of cognitive impairment as measured by the Mini‐Mental State Examination. Methods: Thirty AD, 19 VaD and 29 controls patients were recruited to the study. Plasma levels of malondialdehyde (MDA), total sulfhydryl (T‐SH), calcium (Ca⁺⁺) and magnesium (Mg⁺⁺) were measured. Results: In both AD and VaD groups, the levels of oxidative stress parameters were higher compared with controls. Further, the VaD patients expressed significantly higher levels of plasma parameters of oxidative stress than AD. The difference was noted in MDA, the marker of lipid peroxidation, whereas in VaD the level of MDA was more than 2.8‐fold higher than that registered in AD patients. Conclusion: Vascular dementia in patients is characteristic of increased levels of oxidative stress, especially lipid peroxidation markers. This finding is relevant to determining the pathophysiology of dementia, particularly in the light of the recently suggested importance of the vascular component in dementia development, in addition to aiding in the diagnosis of VaD following clinical presentation. The study will be continued to compare the character and level of decline in both groups.     

The lipid peroxidation products as possible markers of Alzheimer's disease in blood

Oxidative stress, which is present in Alzheimer's disease (AD), results in the formation of various end-products of free radical reactions with proteins and lipids. At present there are no reliable diagnostic biomarkers of AD in the blood. Therefore, specific products of lipid peroxidation in the blood of AD patients were investigated. Lipophilic extracts of erythrocytes in the group of patients with AD (n = 44) and age-matched controls (n = 16) were studied. The end-products of lipid peroxidation, so called lipofuscin-like pigments (LFP), were analysed by fluorescence spectroscopy. It was found that the level of these products is significantly increased in erythrocytes of AD patients compared to controls. LFP were further separated by means of HPLC into individual fractions to study their composition in AD and controls. The specific fraction of LFP in AD patients, which was isolated, might represent a disease-specific product in the blood.