Current Alzheimer Research - Volume 18, Issue 14, 2021

Background: Dynamic cerebral autoregulation (dCA) remains intact in both ageing and dementia, but studies of neurovascular coupling (NVC) have produced mixed findings. Objective: We investigated the effects of task-activation on dCA in healthy older adults (HOA), and patients with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). Methods: Resting and task-activated data from thirty HOA, twenty-two MCI, and thirty-four AD were extracted from a database. The autoregulation index (ARI) was determined at rest and during five cognitive tasks from transfer function analysis. NVC responses were present where group-specific thresholds of cross-correlation peak function and variance ratio were exceeded. Cumulative response rate (CRR) was the total number of positive responses across five tasks and two hemispheres. Results: ARI differed between groups in dominant (p=0.012) and non-dominant (p=0.042) hemispheres at rest but not during task-activation (p=0.33). ARI decreased during language and memory tasks in HOA (p=0.002) but not in MCI or AD (p=0.40). There was a significant positive correlation between baseline ARI and CRR in all groups (r=0.26, p=0.018), but not within sub-groups. Conclusion: dCA efficiency was reduced in task-activation in healthy but not cognitively impaired participants. These results indicate differences in neurovascular processing in healthy older adults relative to cognitively impaired individuals.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that has been characterized by progressive development of long onset early disease with complicated etiology and may cause memory loss, cognitive impairment, and behavioral changes. Physical exercise may play a preventive role in AD. In the present study, we investigated the impact of longer-term physical exercise on the finger tapping of AD patients by comparing the finger tapping of AD patients and healthy controls. Methods: In this study, 140 subjects aged ≥ 60 years were enrolled. Group A consisted of 70 subjects (27 males and 43 females) without exercise habits who were selected from Yangpu District (Shanghai, China). Group B consisted of 70 subjects (27 males and 43 females) who were selected from Minxing District (Shanghai, China). All the subjects were right-handed as well. The subjects’ data, including subjects’ age, weight, height, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and finger tapping frequency, were measured. Results: The subjects were matched in age, weight, and height. The AD subjects’ MoCA and MMSE scores were noticeably lower than healthy subjects’ scores (P<0.001); besides, AD patients with exercise had significantly lower MoCA and MMSE scores than healthy controls with exercise (P<0.001). The finger tapping of AD subjects’ left hands was significantly lower than that of healthy subjects without AD (P<0.01), and AD subjects with exercise tapped significantly slower with their left hand than healthy subjects with exercise (P<0.01). Meanwhile, AD subjects with exercise tapped significantly faster with the left hand than AD subjects (P<0.05). The right hands of AD subjects tapped remarkably less than healthy subjects (P<0.01) with or without exercise. Meanwhile, subjects with exercise tapped significantly faster with their right hand than healthy subjects (P<0.05), and AD subjects with exercise tapped significantly faster with their right hand than AD subjects (P<0.05). Conclusion: Long-term physical exercises can improve finger tapping frequency, especially in patients with AD. Finger tapping frequency may be used as an index to monitor the cognitive decline in ageing AD patients.

Background: Alzheimer’s Disease (AD) is still a great global challenge and agents with various mechanisms represent a promising therapeutic opportunity. Theracurmin, a very highly absorbable curcumin formulation, was shown to improve memory and attention in non-demented people. Objective: The aim of the study was to investigate the effect of Theracurmin on disease course in elderly patients with mild cognitive impairment (MCI) and AD. Methods: This follow-up study was performed retrospectively on 93 patients with MCI or AD. All patients underwent comprehensive geriatric assessment, including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), clock-drawing test, activities of daily living (ADL), at baseline and at the end of the 6th month. 19 patients with AD and 17 with MCI were treated with Theracurmin 180 mg/day per oral. Results: MMSE, MOCA and instrumental ADL scores decreased in AD patients not treated with Theracurmin (p<0.001, p=0.011, and p=0.004, respectively), whereas these scores remained stable in those treated with Theracurmin. This stabilization in the instrumental ADL was also observed in MCI patients treated with Theracurmin. During the follow-up, three MCI patients who did not receive Theracurmin progressed to AD, whereas only one patient progressed in those who received it. Conclusion: Theracurmin seems to be a therapeutic option for elderly patients with AD and MCI via providing stabilization of the disease course by preventing progressive loss in cognitive functions and ADLs.

Objective: The objective of this study is to examine the association of olfactory function and genetic predisposition of Alzheimer’s disease (AD) with cognitive performance in adults. Methods: A total of 2049 Chinese adults from Rugao Longevity and Ageing Study (RuLAS, n=1460, mean age 78 years) and Central China Cohort (CCC, n=589, mean age 48 years) were included in this study. A standard interview-based survey, clinical information, and blood samples were collected in both cohorts. Olfactory function in terms of olfactory identification was measured by the brief version of the Chinese Smell Identification Test consisted of 18 full points. Cognitive performance was measured by the Chinese version of the Mini-mental State Examination. A genetic risk score (GRS) was calculated from 5 single nucleotide polymorphisms, which were robustly related to Alzheimer’s disease in Caucasians and cognitive performance in our Chinese population. Results: In the pooled analyses, participants at the lowest quartile of olfactory function had significantly higher odds of cognitive impairment (adjusted odds ratio [95% CI] =1.45 [1.00 to 2.09], Ptrend =0.005), and such association was stronger among participants with a stronger genetic predisposition of Alzheimer’s disease (β coefficient±SE, -0.06±0.03 in participants with a lower GRS vs. -0.19±0.05 in those with a higher GRS, respectively, Pinteraction=0.01). Similar associations were observed in RuLAS (P-trend=0.06) and in CCC (P-trend<0.001). Conclusion: In this study, a decreased olfactory function was associated with worse cognitive performance in adults, especially among participants with a higher genetic risk of Alzheimer’s disease. Further studies are warranted to evaluate the causal relationship between olfaction and cognitive performance.

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p <0.001), whereas AD subjects had a lower BR than HCs (p <0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

Background: The aim of this study was to establish the validity and reliability of the Computerized Brief Cognitive Screening Test (CBCog) for early detection of cognitive impairment. Methods: One hundred and sixty participants, including community-dwelling and out-patient volunteers (both men and women) aged ≥ 65 years, were enrolled in the cross section study. All participants were screened using the CBCog and Mini-Mental State Examination (MMSE). The internal consistency of the CBCog was analyzed using Cronbach’s α test. Areas under the curves (AUCs) of receiver operating characteristic analyses were used to test the predictive accuracy of the CBCog in detecting mild cognitive impairment (MCI) in order to set an appropriate cutoff point. Results: The CBCog scores were positively correlated with the MMSE scores of patients with MCI-related dementia (r = 0.678, P < .001). The internal consistency of the CBCog (Cronbach’s α) was 0.706. It was found that the CBCog with a cutoff point of 19/20 had a sensitivity of 97.5% and a specificity of 53.7% for the diagnosis of MCI with education level ≥ 6 years. The AUC of the CBCog for discriminating the normal control elderly from patients with MCI (AUC = 0.827, P < 0.001) was larger than that of the MMSE for discriminating the normal control elderly from patients with MCI (AUC= 0.819, P < .001). Conclusion: The CBCog demonstrated to have sufficient validity and reliability to evaluate mild cognitive impairment, especially in highly educated elderly people.

Background: Although clusterin-a protein involved in lipid metabolism, amyloid beta clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at risk for Alzheimer’s disease, research exploring associations with white matter (WM) micro- and macro- structural markers are largely limited. Objective: The current study explored associations between serum clusterin protein levels and WM micro- and macro- structural markers, and clarified whether variations in WM fractional anisotropy (FA) were associated with functional abilities within in a racially homogenous sample of relatively well-educated older adults free of dementia. Methods: Participants underwent magnetic resonance imaging (MRI) brain exams and a blood draw and completed a performance-based measure of everyday functioning. Multiple linear regression adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin associations with WM metrics, as well clarify potential links between WM microstructure and everyday functioning. Results: Higher serum clusterin was associated with lower FA in several thalamocortical (anterior and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02). Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but higher FA of several WM tracts was associated with better performance on the Independent Living Scale (ßs = .37 to .53, ps = .006 to .03). Conclusions: Serum clusterin is differentially associated with WM metrics, and WM microstructure is associated with everyday functioning.

Introduction: This study aimed to build the supervised learning model to predict the state of cognitive impairment, Alzheimer’s Disease (AD) and cognitive domains including memory, language, action, and visuospatial based on Digital Clock Drawing Test (dCDT) precisely. Methods: 207 normal controls, 242 Mild Cognitive Impairment (MCI) patients, 87 dementia patients, including 53 AD patients, were selected from Shanghai Tongji Hospital. The electromagnetic tablets were used to collect the trajectory points of dCDT. By combining dynamic process and static results, different types of features were extracted, and the prediction models were built based on the feature selection approaches and machine learning methods. Results and Discussion: The optimal AUC of cognitive impairment’s screening, AD’s screening and differentiation are 0.782, 0.919 and 0.818, respectively. In addition, the cognitive state of the domains with the best prediction result based on the features of dCDT is action with the optimal AUC 0.794, while the other three cognitive domains got the prediction results between 0.744-0.755. Conclusion: By extracting dCDT features, cognitive impairment and AD patients can be identified early. Through dCDT feature extraction, a prediction model of single cognitive domain damage can be established.

Background: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer’s disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer’s disease. Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. Methods: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. Results: The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. Conclusion: We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer’s disease.