scholarly journals Association of Accelerated Long-term Forgetting and Senescence-related Blood-borne Factors in Asymptomatic Individuals From Families With Autosomal Dominant Alzheimer’s Disease

2021 ◽  
Author(s):  
Jianwei Yang ◽  
Chaojun Kong ◽  
Longfei Jia ◽  
Tingting Li ◽  
Meina Quan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Word List ◽  
Related Factors ◽  
Blood Concentrations ◽  
Mutation Carriers ◽  
Asymptomatic Individuals ◽  
Three Delays

Abstract Background: Accelerated long-term forgetting has been identified in preclinical Alzheimer’s disease (AD), and is attributed to a selective impairment of memory consolidation in which hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD). Methods: We analyzed data of 39 asymptomatic participants (n=18 ADAD mutation carriers, n=21 non-carriers) from the Chinese Familial Alzheimer’s Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min and 7 days. Peripheral blood concentrations of candidate pro-aging factors (C-C motif ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants. Results: Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall (β= -0.46, p=0.002), figure recall (β= -0.44, p=0.004) and list recognition (β= -0.37, p=0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: β=0.39, p=0.007; CCL11 versus list recognition: β=0.44, p=0.002).Conclusions: Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting.

scholarly journals Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianwei Yang ◽  
Chaojun Kong ◽  
Longfei Jia ◽  
Tingting Li ◽  
Meina Quan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Word List ◽  
Related Factors ◽  
Blood Concentrations ◽  
Mutation Carriers ◽  
Chemokine Ligand ◽  
Asymptomatic Individuals

Abstract Background Accelerated long-term forgetting has been identified in preclinical Alzheimer’s disease (AD) and is attributed to a selective impairment of memory consolidation in which the hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD). Methods We analyzed data of 39 asymptomatic participants (n = 18 ADAD mutation carriers, n = 21 non-carriers) from the Chinese Familial Alzheimer’s Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min, and 7 days. Peripheral blood concentrations of candidate pro-aging factors (CC chemokine ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants. Results Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall (β = −0.46, p = 0.002), figure recall (β = −0.44, p = 0.004), and list recognition (β = −0.37, p = 0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: β = 0.39, p = 0.007; CCL11 versus list recognition: β = 0.44, p = 0.002). Conclusions Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Jairo E. Martinez ◽  
Enmanuelle Pardilla-Delgado ◽  
Edmarie Guzmán-Vélez ◽  
Clara Vila-Castelar ◽  
Rebecca Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Decline ◽  
Verbal Memory ◽  
Autosomal Dominant ◽  
Memory Performance ◽  
Subjective Cognitive Decline ◽  
Mutation Carriers ◽  
Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

scholarly journals Impairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers

2018 ◽  
Vol 65 ◽  
pp. 149-157 ◽  
Author(s):  
Jessica R. Petok ◽  
Catherine E. Myers ◽  
Judy Pa ◽  
Zachary Hobel ◽  
David M. Wharton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Disease Mutation ◽  
Mutation Carriers ◽  
Autosomal Dominant Alzheimer’S Disease

scholarly journals 0421 Decreased Actigraphic Daytime Activity is Associated with Lower Memory Performance in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A161-A161
Author(s):  
E Pardilla-Delgado ◽  
L Ramirez Gomez ◽  
A Y Baena ◽  
M I Montes ◽  
Y Bocanegra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Word List ◽  
Brain Regions ◽  
Future Research ◽  
Daytime Activity ◽  
Mutation Carriers ◽  
Wrist Actigraphy ◽  
Circadian Dysfunction

Abstract Introduction Alzheimer’s disease (AD) impacts brain regions that control circadian regulation systems such as wakefulness and daytime physical activity. Recent evidence shows that AD pathology is damaging for wake-promoting neurons. Whether early changes in wakefulness and daytime activity occur during asymptomatic stages of familial AD (fAD) remains unknown. In this study, we aimed to investigate whether daytime activity differs between cognitively-unimpaired carriers of early-onset fAD and age-matched non-carrier family members. Further, we examined the associations between daytime activity and memory performance. Methods A total of 25 members of the large Colombian kindred with the Presenilin1 (PSEN1) E280A mutation were included in the study (9 mutation carriers and 16 non-carriers, mean age=38.2). PSEN1 mutation carriers develop dementia before the age of 50. All subjects underwent wrist actigraphy for 7-14 days to measure daytime activity (average activity per minute and per epoch), and completed the CERAD Word List Learning and the Free and Cued Selective Reminding Test (FCSRT). Results Compared to non-carriers, mutation carriers had less average daytime activity (Mann-Whitney U Test p=.04). Higher average daytime activity was associated with better memory recall in both the CERAD word list delayed recall (r=.47, p=.05) and the FCRST delayed total recall (r=.53, p=.02). No associations with age were observed. Conclusion Our results suggest that cognitively-unimpaired mutation carriers have reduced daytime activity, years before the onset of dementia. Reduced daytime activity in carriers is also associated with lower memory performance. Our preliminary findings add to the growing evidence that circadian dysfunction is present in early AD, and may play an important role in subsequent memory impairment. Future research with large samples is needed to further examine sleep and circadian dysfunction in asymptomatic individuals at genetic risk for AD. Support NIA 5R01AG054671-03 to YTQ

scholarly journals Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Lisa Vermunt ◽  
Ellen Dicks ◽  
Guoqiao Wang ◽  
Aylin Dincer ◽  
Shaney Flores ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Symptom Onset ◽  
Grey Matter ◽  
Autosomal Dominant ◽  
Single Subject ◽  
Mutation Carriers ◽  
Autosomal Dominant Alzheimer’S Disease ◽  
Network Properties ◽  
Over Time

Abstract Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer’s disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset −9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer’s disease, which is alike sporadic Alzheimer’s disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer’s disease.

scholarly journals The Nordic diet and cognition – The DR's EXTRA Study

2015 ◽  
Vol 114 (2) ◽  
pp. 231-239 ◽  
Author(s):  
Reija Männikkö ◽  
Pirjo Komulainen ◽  
Ursula Schwab ◽  
Harri M. Heikkilä ◽  
Kai Savonen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positive Association ◽  
Word List ◽  
Population Based ◽  
Lifestyle Factor ◽  
Related Factors ◽  
Cross Sectional ◽  
Nordic Diet ◽  
Diet Score

The rapid increase in the prevalence of dementia associated with ageing populations has stimulated interest in identifying modifiable lifestyle factors that could prevent cognitive impairment. One such potential preventive lifestyle factor is the Nordic diet that has been shown to reduce the risk of CVD; however, its effect on cognition has not been studied. The aim of the present study was to estimate the cross-sectional and longitudinal associations of the baseline Nordic diet with cognitive function at baseline and after a 4-year follow-up in a population-based random sample (n1140 women and men, age 57–78 years) as secondary analyses of the Finnish Dose-Responses to Exercise Training study. The Nordic diet score was created based on reported dietary components in 4-d food records. Cognition was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery and the Mini-mental State Examination (MMSE). The baseline Nordic diet score had been positively associated with Verbal Fluency (β 0·08 (95 % CI 0·00, 0·16),P= 0·039) and Word List Learning (β 0·06 (95 % CI 0·01, 0·10),P= 0·022) at 4 years but not with the Consortium to Establish a Registry for Alzheimer's Disease total score (CERAD-TS) or MMSE at 4 years, after adjustment for baseline cognitive scores, demographic factors and health-related factors. After excluding individuals with impaired cognition at baseline, the baseline Nordic diet score had also been positively associated with the CERAD-TS (β 0·10 (95 % CI 0·00, 0·20),P= 0·042) and MMSE (β 0·03 (95 % CI 0·00, 0·06),P= 0·039) at 4 years. These associations disappeared after further adjustment for energy intake. In conclusion, the Nordic diet might have a positive association with cognition in individuals with normal cognition.

scholarly journals Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer's disease

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alexa Pichet Binette ◽  
Guillaume Theaud ◽  
François Rheault ◽  
Maggie Roy ◽  
D Louis Collins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Autosomal Dominant ◽  
Mean Diffusivity ◽  
Free Water ◽  
Tau Proteins ◽  
Uncinate Fasciculus ◽  
Mutation Carriers ◽  
White Matter Microstructure

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focussed on free-water corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

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