Memory Binding Test and Its Associations With Hippocampal Volume Across the Cognitive Continuum Preceding Dementia

Innovative memory paradigms have been introduced to capture subtle memory changes in early Alzheimer’s disease (AD). We aimed to examine the associations between different indexes of the challenging Memory Binding Test (MBT) and hippocampal volume (HV) in a sample of individuals with subjective cognitive decline (SCD; n = 50), amnestic mild cognitive impairment (aMCI) due to AD ( n = 31), and cognitively normal (CN) older adults ( n = 29) recruited from the Czech Brain Aging Study, in contrast to traditional verbal memory tests. Both MBT free and cued recall scores in immediate and delayed recall conditions were associated with lower HV in both SCD and aMCI due to AD, whereas in traditional verbal memory tests only delayed recall scores were associated with lower HV. In SCD, the associations with lower HV in the immediate recall covered specific cued recall indexes only. In conclusion, the MBT is a promising test for detecting subtle hippocampal-associated memory decline during the predementia continuum.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

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.

Depressive Symptoms, Subjective Cognitive Decline, and Subjective Sleep Quality Are Associated with Slips and Falls: Data from the Community Health Survey in Korean Adults

<b><i>Background:</i></b> Identifying the risk factors for falls among the elderly population is arguably one of the most imperative public health issues in the current aging society. <b><i>Objectives:</i></b> This study aimed to determine the associations between depressive symptoms, subjective cognitive decline (SCD), and poor subjective sleep quality and the risk of slips/falls in a Korean older population. <b><i>Methods:</i></b> This cross-sectional study involved 228,340 elderly individuals living in Korea. Measurements included self-reported depressive symptoms, SCD, and self-reported sleep quality. The risk of slips/falls was dichotomized depending on whether slips/falls had occurred during the past year, and the associations between different risk factors and slips/falls were explored. Multiple logistic regression was used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Complex sampling methods were used to estimate the weighted value of each participant. <b><i>Results:</i></b> The risk of slips/falls was significantly associated with high levels of depressive symptoms (adjusted OR 1.06, 95% CI: 1.05–1.07) and SCD (adjusted OR 1.33, 95% CI: 1.19–1.50). Regarding each sleep quality component, the adjusted ORs for slips/falls were 1.85 for very poor sleep quality, 1.49 for long sleep latency, 1.04 for &#x3c;5 h of sleep duration, 1.32 for low sleep efficiency, 2.78 for high sleep disturbance, 1.52 for the use of sleep medication ≥3 times a week, and 1.82 for high daytime dysfunction due to sleep problems compared to the respective good sleep conditions. <b><i>Conclusions:</i></b> Our results demonstrated that depressive symptoms, SCD, and poor subjective sleep quality are independent factors affecting the occurrence of slips/falls. Thus, efforts to manage depressive symptoms and cognitive decline early and to improve sleep quality can be an alternative strategy to decrease the likelihood of falls.

Difference in Amyloid Load Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Study from the SILCODE

Background: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer’s disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. Objective: We aims to explore the differences in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. Methods: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. Results: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. Conclusion: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.

The role of Mediterranean diet in the course of subjective cognitive decline in the elderly population of Greece: results from a prospective cohort study

Very few data are available regarding the association of adherence to the Mediterranean Diet (MeDi) with Subjective Cognitive Decline (SCD) evolution over time. A cohort of 939 cognitively normal individuals reporting self-experienced, persistent cognitive decline not attributed to neurological, psychiatric or medical disorders from the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD study) was followed-up for a mean period of 3.10 years. We defined our SCD score as the number of reported SCD domains (memory, language, visuoperceptual and executive), ranging from 0 to 4. Dietary intake at baseline was assessed through a food frequency questionnaire; adherence to the MeDi pattern was evaluated through the Mediterranean Diet Score (MDS) that ranged from 0 to 55, with higher values indicating greater adherence to the MeDi. The mean SCD score in our cohort increased by 0.20 cognitive domains during follow-up. After adjustment for multiple potential confounders, we showed that an MDS higher by 10 points was associated with a 7% reduction in the progression of SCD within one year. In terms of food groups, every additional vegetable serving consumption per day was associated with a 2.3% reduction in SCD progression per year. Our results provide support to the notion that MeDi may have a protective role against the whole continuum of cognitive decline, starting at the first subjective complaints. This finding may strengthen the role of the MeDi as a population-wide, cost-effective preventive strategy targeting the modifiable risk factors for cognitive decline.

Intervening factors in the perception of memory decline and life purpose in older adults

Objective: To investigate the relationship between the perception of memory decline and the purpose of life in the elderly.Methods: A cross-sectional study that evaluated 235 older adults living in the city of Maringá, Paraná. A sociodemographic questionnaire, the Life Purpose Scale and the Subjective Cognitive Decline Initiative (SCD-I) were used. Data analysis was conducted using the Kolmogorov-Smirnov, Mann–Whitney “U”, Kruskal-Wallis, and Pearson's Chi-square tests (p < 0.05). Results: The results showed a higher prevalence of women with a perception of memory decline (p = 0.011) and that the elderly with more than three minimum wages had higher scores on the life purpose scale than the elderly with lower income. It was found that the elderly who does not consider that the deterioration of memory affects activities of daily living (ADL) had a greater purpose in life than the elderly who considers that the deterioration of memory impairs their ADL (p = 0.004). Conclusion: female gender seems to be a factor associated with memory decline, while higher monthly income seems to be an intervening factor in the greater purpose of life of the elderly. Not considering that memory loss harms ADLs, it seems to intervene in the best purpose of life.

Association of CSF Aβ38 Levels With Risk of Alzheimer Disease–Related Decline

Objective:Experimental studies suggest that the balance between short and long Aβ species might modulate the toxic effects of Aβ in Alzheimer’s disease (AD) but clinical evidence is lacking. We studied whether Aβ38 levels in cerebrospinal fluid (CSF) relate to risk of AD dementia and cognitive decline.Methods:CSF Aβ38 levels were measured in 656 individuals across two clinical cohorts – the Swedish BioFINDER study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cox regression models were used to evaluate the association between baseline Aβ38 levels and risk of AD dementia in AD-biomarker positive individuals (AD+; determined by CSF P-tau/Aβ42 ratio) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Linear mixed effects models were used to evaluate the association between baseline Aβ38 levels and cognitive decline as measured by the Mini-Mental State Examination (MMSE) in AD+ participants with SCD, MCI or AD dementia.Results:In the BioFINDER cohort, high Aβ38 levels were associated with slower decline in MMSE (β = 0.30 points / sd., P = 0.001) and with lower risk of conversion to AD dementia (HR = 0.83 per sd., P = 0.03). In the ADNI cohort, higher Aβ38 levels were associated with less decline in MMSE (β = 0.27, P = 0.01), but not risk of conversion to AD dementia (P = 0.66). Aβ38 levels in both cohorts were significantly associated with both cognitive and clinical outcomes when further adjusted for CSF P-tau or CSF Aβ42 levels.Interpretation:Higher CSF Aβ38 levels are associated with lower risk of AD-related changes in two independent clinical cohorts. These findings suggest that γ-secretase modulators could be effective as disease-altering therapy.

Network-level permutation entropy of resting-state MEG recordings: a novel biomarker for early-stage Alzheimer’s disease?

Objective. Increasing evidence suggests that measures of signal variability and complexity could present promising biomarkers for Alzheimer’s disease (AD). Earlier studies have however been limited to the characterization of local activity. Here, we investigate whether a network version of permutation entropy could serve as a novel biomarker for early-stage AD. Methods. Resting-state source-space magnetoencephalography was recorded in 18 subjects with subjective cognitive decline (‘SCD’) and 18 subjects with mild cognitive impairment (‘MCI’). Local activity was characterized by permutation entropy (PE). Network interactions were studied using the inverted Joint Permutation Entropy (JPEinv), corrected for volume conduction. Results. The JPEinv showed a reduction of nonlinear connectivity in MCI subjects in the theta and alpha band. Local PE showed increased theta-band entropy. Between-group differences were widespread across brain regions. ROC analysis of classification of MCI versus SCD subjects revealed that a linear regression model trained on JPEinv features (78.4% [62.5–93.3%]) slightly outperformed PE (76.9% [60.3–93.4%]) and relative theta power based models (76.9% [60.4–93.3%]). Conclusion. Classification performance of theta JPEinv was at least as good as the relative theta power benchmark. The JPEinv is therefore a potential biomarker for early-stage AD, and should be explored in larger studies.