Current Alzheimer Research - Volume 18, Issue 3, 2021

Objective: This study investigated the relationship between neural activities and retinal structures associated with working memory (WM) in older adults with mild cognitive impairment (MCI). Methods: Eleven older adults with MCI and 29 healthy controls (60 to 73 years old) were tested. All participants underwent an event-related potential (ERP) recording while performing the two-back memory task. The Optical coherence tomography angiography (OCT-A) was administered to examine the perfusion and vessel density in the retina. Results: Results showed that WM performance in the MCI group was negatively associated with ERP latencies in central parietal regions (CP6 and CP8) (ps< 0.05). The left nasal vessel and perfusion densities were negatively correlated with the latencies in these two central parietal regions and positively related to WM performance only in the MCI group (ps< 0.05). Conclusion: The findings on WM, central parietal brain activity, and left nasal vessel and perfusion densities in the retina help us gain a better understanding of the neural and retinal underpinnings of WM in relation to MCI.

Background: Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Objective: We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage. Methods: We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined. Results: In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL. Conclusion: The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Background: Alzheimer's disease (AD) is the most common type of dementia and has a complex pathogenesis with no effective treatment. Energy metabolism disorders, as an early pathological event of AD,have attracted attention as a promising area of AD research. Codonopsis pilosula Polysaccharides are the main effective components of Codonopsis pilosula, which have been demonstrated to regulate energy metabolism. Methods: In order to further study the roles and mechanisms of Codonopsis pilosula polysaccharides in AD, this study used an Aβ1-40-induced PC12 cells model to study the protective effects of Codonopsis pilosula polysaccharides and their potential mechanisms in improving energy metabolism dysfunction. Results: The results showed that Aβ1-40 induced a decrease in PC12 cells viability, energy metabolism molecules (ATP, NAD+, and NAD+/NADH) and Mitochondrial Membrane Potential (MMP) and an increase in ROS. Additionally, it was found that Aβ1-40 increased CD38 expression related to NAD+ homeostasis, whereas Silent Information Regulation 2 homolog1 (SIRT1, SIRT3), Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and SIRT3 activity were decreased. Codonopsis pilosula polysaccharides increased NAD+, NAD+/NADH, SIRT3, SIRT1, and PGC-1α related to NAD+, thus partially recovering ATP. Conclusion: Our findings reveal that Codonopsis pilosula polysaccharides protected PC12 cells from Aβ1-40-induced damage, suggesting that these components of the Codonopsis pilosula herb may represent an early treatment option for AD patients.

Background and Objective: Research has documented the stigma that individuals with degenerative neurological diseases experience, but caregivers also experience stigma by association (i.e., affiliate stigma). In order to shed light on the stigma of caregivers of people with degenerative neurological diseases, the current study aimed to explore cross-cultural differences in the prevalence of Parkinson’s disease (PD) caregiver affiliate stigma, as well as the relationship between PD symptoms and caregiver affiliate stigma. Applications for Alzheimer’s disease are discussed. Methods: Survey data were collected in PD clinics at public, academic medical centers. Informal caregivers of an individual with PD from the US (n = 105) and from Mexico (n = 148) participated in the study. Caregivers completed a questionnaire that included the MDS Unified PD Rating Scale to describe the symptoms of the individual with PD, as well as the Affiliate Stigma Scale and demographic information. Results: A series of multiple regressions was run to examine whether PD symptoms were associated with affiliate stigma and if these differed by country. These regressions suggested that different patterns of PD symptoms predicted affiliate stigma in each country. Stigma was higher in the US compared to Mexico, and the relationship between bowel/bladder symptoms and affiliate stigma was significantly stronger in the US. Conclusion: Symptoms of individuals with neurodegenerative diseases are related to affiliate stigma experienced by caregivers, and these relationships may differ cross-culturally. Negative public attitudes concerning bowl and bladder issues and the physical symptoms that accompany PD remain a source of stigma for caregivers and families, particularly in the US. Interventions for caregivers of individuals with neurodegenerative diseases should include strategies for coping with stigma concerning bladder and bowel problems, as well as other physical and mental health issues.

Background: Cognitive dysfunction, particularly in Alzheimer’s disease (AD), seriously affects the health and quality of life of older adults. Early detection can prevent and slow cognitive decline. Objective: This study aimed at evaluating the role of socio-demographic variables, lifestyle, and physical characteristics in cognitive decline during AD progression and analyzing the probable causes and predicting stages of the disease. Methods: By analyzing data of 301 subjects comprising normal elderly and patients with mild cognitive impairment (MCI) or AD from six communities in Taiyuan, China, we identified the influencing factors during AD progression by a Logistic Regression model (LR) and then assessed the associations between variables and cognition using a Bayesian Networks (BNs) model. Results: The LR revealed that age, sex, family status, education, income, character, depression, hypertension, disease history, physical exercise, reading, drinking, and job status were significantly associated with cognitive decline. The BNs model revealed that hypertension, education, job status, and depression affected cognitive status directly, while character, exercise, sex, reading, income, and family status had intermediate effects. Furthermore, we predicted probable cognitive stages of AD and analyzed probable causes of these stages using a model of causal and diagnostic reasoning. Conclusion: The BNs model lays the foundation for causal analysis and causal inference of cognitive dysfunction, and the prediction model of cognition in older adults may help the development of strategies to control modifiable risk factors for early intervention in AD.

Background: Reading fluency is essential for our functioning in the literate society in which we live. Reading expressiveness or prosody, along with speed and accuracy, are considered key aspects of fluent reading. Prosodic patterns may vary, not being the same in children learning to read as in adulthood. But little is known about the prosodic characteristics and reading fluency of people with neurodegenerative diseases that causes language impairment and reading difficulties, such as Alzheimer’s disease (AD). Objective: The aim of this work was to study reading fluency in AD, considering reading speed, accuracy and reading prosody. Methods: The participants were 20 healthy elderly Spanish adults, and 20 AD patients, aged 64-88 years. An experimental text was designed, that included declarative, exclamatory, and interrogative sentences, words with different stresses and low-frequency words. The reading of the participants was recorded and analyzed using Praat software. Results: The AD group showed significantly longer reading duration, both at the syllable level and at the word and sentence level. These patients also committed more pauses between words, which were also longer, and more reading errors. The control group showed a variation of the syllabic F0 in the three types of sentences, while these variations only appeared in declarative ones in the AD group. Conclusion: The pauses, along with the slight pitch variations and the longer reading times and errors committed, compromise the reading fluency of people with AD. Assessment of this reading feature could be interesting as a possible diagnostic marker for the disease.

Background: Recent findings suggest a possible role of diet, particularly nutrient intakes and dietary patterns, in the prevalence of mild cognitive impairment (MCI); few studies, however, have been explicitly devoted to the relationship between dietary habits and MCI. Objectives: We aimed to explore the association between dietary habits, including meal timing, and MCI among older Chinese adults. Methods: This cross-sectional study involved data collected at the baseline of the Tianjin Elderly Nutrition and Cognition Cohort (TENCC) study, in which 3,111 community-dwelling older adults (326 MCI patients and 2,785 non-MCIs) from a rural area of Tianjin, China, were recruited. In March 2018 to June 2019, all participants underwent a detailed neuropsychological evaluation that allowed for psychometric MCI classification. Information on self-reported dietary behaviors was gathered via face-to-face interviews. Crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Results: In the multivariable-adjusted models, eating breakfast 4 to 6 times per week (vs. ≤3 times per week, OR: 0.45; 95% CI: 0.26, 0.75), drinking water before breakfast (yes vs. no, OR: 0.64; 95% CI: 0.51, 0.82), consuming water ≥1.5L per day (vs. <1.5L per day, OR: 0.64; 95% CI: 0.51, 0.82), and having lunch after 12:00 (vs. before 12:00, OR: 0.59; 95% CI: 0.47, 0.75) were associated with decreased risk of MCI. Participants who consumed higher amounts of cooking oil were at a higher risk of MCI (moderate vs. low, OR: 1.42; 95% CI: 1.04, 1.92; high vs. low, OR: 1.40; 95% CI: 1.07-1.83). Conclusion : This study suggests that dietary habits, including breakfast frequency, daily water consumption, cooking oil consumption, and meal timing, may be associated with the risk of MCI. If replicated, these findings would open new possibilities of dietary interventions for MCI.

Background: Alzheimer’s disease with a causative genetic mutation (AD-CGM) is an uncommon form, characterized by a heterogeneous clinical phenotype and variations in the genotype of racial groups affected. Objective: We aimed to systemically describe the phenotype variance and mutation spectrum in the large sample size of the Peking Union Medical College Hospital (PUMCH) cohort, Beijing, China. Methods: Next-generation sequencing (NGS) was carried out in 1108 patients diagnosed with dementia. A total of 40 Han Chinese patients with three AD gene mutations were enrolled. A systemic review of all the patients was performed, including clinical history, neurocognitive assessment, brain magnetic resonance imaging, and cerebrospinal fluid (CSF) biomarkers. Results: We studied the following gene mutation variants: 12 AβPP, 13 PSEN1, and 9 PSEN2, and 23 among them were novel. Most of them were early-onset, but PSEN1 mutation carriers had the youngest onset age. The commonest symptoms were similar to those of AD, including an amnestic syndrome, followed by psychiatric symptoms and movement disorder. On MRI, parietal and posterior temporal atrophy was prominent in PSEN1 and PSEN2 mutation carriers, while AβPP mutation carriers had more vascular changes. The CSF biomarkers profile was indistinguishable from sporadic AD. Conclusion: We identified a small group of AD-CGM subjects representing 3.6% among more than 1000 demented patients in the PUMCH cohort. These subjects usually presented with early-onset dementia and exhibited significant clinical and genetic heterogeneity. Identification required complete screening of genetic mutations using NGS. Although family history was usually present, we found non-familial cases of all three genetic mutations.