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

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽  
2014 ◽  
Vol 27 (4) ◽  
pp. 161-169 ◽  
Author(s):  
Nienke A. Hofrichter ◽  
Sandra Dick ◽  
Thomas G. Riemer ◽  
Carsten Schleussner ◽  
Monique Goerke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serial Position ◽  
Episodic Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Word List ◽  
Position Effects ◽  
Serial Position Effects ◽  
List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

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 Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer’s disease

2020 ◽  
Author(s):  
Xiong Jiang ◽  
James H. Howard ◽  
G. Wiliam Rebeck ◽  
R. Scott Turner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Inhibition Of Return ◽  
Memory Performance ◽  
Brain Regions ◽  
List Type ◽  
Older Individuals

ABSTRACTSpatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here we provide evidence supporting that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD), and the impairment is readily detectable using a novel double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the novel double cue spatial IOR paradigm may be useful in detecting MCI and early AD.SIGNIFICANCE STATEMENTNovel double cue spatial inhibition of return (IOR) paradigm revealed a robust effect IOR deficits in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD)Spatial IOR effect correlates with memory performance in healthy older adults at a elevated risk of Alzheimer’s disease (with a family history or APOE e4 allele)The data suggests that double cue spatial IOR may be sensitive to detect early AD pathological changes, which may be linked to disease progress at the posterior brain regions (rather than the medial temporal lobe)

Implicit Memory Performance of Patients With Alzheimer's Disease: A Brief Review

1995 ◽  
Vol 7 (3) ◽  
pp. 385-392 ◽  
Author(s):  
Marko Jelicic ◽  
Annette E. Bonebakker ◽  
Benno Bonke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Implicit Memory ◽  
Learning Experience ◽  
Memory Performance ◽  
Future Research ◽  
Impaired Performance ◽  
Conscious Recollection ◽  
Previous Learning ◽  
Normal Performance

Memory can be assessed with either explicit or implicit tasks. Implicit memory tasks, in contrast with explicit tasks, do not refer to conscious recollection of a previous learning experience. Implicit memory is revealed by a change in task performance that can be attributed to previous learning. Amnesic patients perform poorly on explicit memory tasks, but exhibit normal performance on implicit tasks. Recently, researchers have studied the implicit memory performance of patients with Alzheimer's disease. This article aims to give an overview of the performance of Alzheimer patients on four tasks of implicit memory. Compared with normal elderly controls, patients with Alzheimer's disease seem to demonstrate impaired performance on conceptual, but not on perceptual, implicit memory tasks. This dissociation could yield important information about the neurologic systems subserving implicit memory processes. Some suggestions for future research into the implicit memory of Alzheimer patients are given.

scholarly journals Low Cerebrospinal Fluid Amyloid-Beta Concentration Is Associated with Poorer Delayed Memory Recall in Women

2016 ◽  
Vol 6 (2) ◽  
pp. 303-312 ◽  
Author(s):  
Fanni Haapalinna ◽  
Teemu Paajanen ◽  
Janne Penttinen ◽  
Hannu Kokki ◽  
Merja Kokki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Memory Performance ◽  
Word List ◽  
Cognitive Status ◽  
Csf Biomarkers ◽  
Memory Disorder ◽  
Biomarker Analysis

Background: Data on the association of memory performance with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are inconsistent. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NB) is a commonly used validated cognitive tool; however, only few studies have examined its relationship with CSF biomarkers for AD. We studied the correlation of pathological changes in CSF biomarkers with various CERAD-NB subtests and total scores. Methods: Out of 79 subjects (36 men, mean age 70.5 years), 63 had undergone an assessment of cognitive status with CERAD-NB and a CSF biomarker analysis due to a suspected memory disorder, and 16 were controls with no memory complaint.Results: In women we found a significant correlation between CSF amyloid-beta (Aβ1-42) and several subtests measuring delayed recall. Word List Recall correlated with all markers: Aβ1-42 (r = 0.323, p = 0.035), tau (r = -0.304, p = 0.050) and hyperphosphorylated tau (r = -0.331, p = 0.046). No such correlations were found in men. Conclusions: CSF biomarkers correlate with delayed memory scores in CERAD-NB in women, and women may have more actual AD pathology at the time of the investigations than men.

scholarly journals Tau pathology in cognitively normal older adults

2019 ◽  
Author(s):  
Jacob Ziontz ◽  
Murat Bilgel ◽  
Andrea T. Shafer ◽  
Abhay Moghekar ◽  
Wendy Elkins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Brain Regions ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Rates Of Change ◽  
Baltimore Longitudinal Study ◽  
Brain Changes ◽  
Male Sex

AbstractINTRODUCTIONTau pathology, a hallmark of Alzheimer’s disease, is observed in the brains of virtually all individuals over 70.METHODSUsing 18F-AV-1451 (18F-flortaucipir) PET, we evaluated tau pathology in 54 cognitively normal participants (mean age 77.5, SD 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between PET signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.RESULTSGreater age, male sex, black race, and amyloid positivity were associated with higher 18F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (β = −1.124, SE = 0.485, p = 0.025) and a steeper decline in memory performance (β = −0.086, SE = 0.039, p = 0.029).DISCUSSIONAssessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer’s disease.

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 Blood metabolite markers of cognitive performance and brain function in aging

2015 ◽  
Vol 36 (7) ◽  
pp. 1212-1223 ◽  
Author(s):  
Brittany N Simpson ◽  
Min Kim ◽  
Yi-Fang Chuang ◽  
Lori Beason-Held ◽  
Melissa Kitner-Triolo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Function ◽  
Memory Performance ◽  
Verbal Learning ◽  
Plasma Concentrations ◽  
Brain Regions ◽  
Older Individuals ◽  
Lower Plasma ◽  
Positron Emission

We recently showed that Alzheimer's disease patients have lower plasma concentrations of the phosphatidylcholines (PC16:0/20:5; PC16:0/22:6; and PC18:0/22:6) relative to healthy controls. We now extend these findings by examining associations between plasma concentrations of these PCs with cognition and brain function (measured by regional resting state cerebral blood flow; rCBF) in non-demented older individuals. Within the Baltimore Longitudinal Study of Aging neuroimaging substudy, participants underwent cognitive assessments and brain 15O-water positron emission tomography. Plasma phosphatidylcholines concentrations (PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6), cognition (California Verbal Learning Test (CVLT), Trail Making Test A&B, the Mini-Mental State Examination, Benton Visual Retention, Card Rotation, and Fluencies—Category and Letter), and rCBF were assessed. Lower plasma phosphatidylcholine concentrations were associated with lower baseline memory performance (CVLT long delay recall task—PC16:0/20:5: −2.17–1.39−0.60 p = 0.001 (β with 95% confidence interval subscripts)) and lower rCBF in several brain regions including those associated with memory performance and higher order cognitive processes. Our findings suggest that lower plasma concentrations of PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6 are associated with poorer memory performance as well as widespread decreases in brain function during aging. Dysregulation of peripheral phosphatidylcholine metabolism may therefore be a common feature of both Alzheimer's disease and age-associated differences in cognition.

High rate of conversion to Alzheimer's disease in a cohort of amnestic MCI patients

2008 ◽  
Vol 20 (1) ◽  
pp. 96-108 ◽  
Author(s):  
Klaus Schmidtke ◽  
Sonja Hermeneit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Word List ◽  
High Rate ◽  
Amnestic Mci ◽  
Prodromal Ad ◽  
List Learning ◽  
Study Population ◽  
Competing Causes

AbstractBackground: A large proportion of patients with amnestic mild cognitive impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion is highly variable, depending on selection and inclusion criteria. In the present prospective study, amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients.Methods: A composite CERAD word list learning z-score of −1 was applied as a cut-off for memory performance at baseline. Competing causes of memory impairment other than prodromal AD were actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were available for follow-up.Results: After a mean delay of 19 months, 44% were found to have converted to AD, corresponding to an annualized conversion rate of 28%. The rate of new diagnoses other than stable MCI or AD was 6%. Baseline neuropsychological variables were not instrumental to predict progression.Conclusion: Amnestic MCI patients, as identified by the present set of criteria, carry a high risk of median-term progression to AD.

scholarly journals 439 - Sex-dependent increase of cerebral blood flow in cortex and hippocampus as a compensatory mechanism in end-of-life dementia: A MRI-ASL translational approach in models of normal and pathological aging

2020 ◽  
Vol 32 (S1) ◽  
pp. 157-157
Author(s):  
A Muntsant-Soria ◽  
F Jiménez-Altayó ◽  
E Jiménez-Xarrié ◽  
L Giménez-Llort
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
End Of Life ◽  
Brain Region ◽  
Memory Performance ◽  
Brain Regions ◽  
Compensatory Mechanism ◽  
Functional Impairments ◽  
Time Asymmetry ◽  
Brain Functions

Alzheimer’s disease (AD) is associated with brain oxidative stress, inflammation, and cerebrovascular disease. Structural and functional abnormalities in cerebral microvasculature have been described in both patients and animals models. New tools and biomarkers for the detection of the disease are still emerging, such as Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for non-invasive measurements of cerebral blood blow (CBF) whose alteration may be involved in AD-pathogenesis. Nevertheless, more studies in the field are needed since both hypoperfusion and hyperperfusion in different brain areas are reported and can be involved in different brain functions. Recently, we reported in our colony of 3xTg-AD mice modeling Alzheimer’s disease a higher number of β-amyloid plaques in the hippocampus and entorhinal cortex in middle-aged females and extensive regions of hypoxia which were not seen in males. In the present study, we evaluated CBF in five different brain regions (hippocampus, cortex, striatum, caudate putamen and amygdala) in older male and female surviving until very advanced-stages of disease and as compared with age-matched counterparts with normal aging. AD-phenotype was evaluated by a comprehensive screening of three main functional impairments: physical (frailty), BPSD-like and cognitive deficits. CBF was measured using MRI-ASL and meaningful correlations between AD-phenotype and CBF were performed to better understand the relation between the level of perfusion and frailty, the BPSD-like behaviors and cognitive impairments. The results indicated sex- and brain region-associated changes in CBF. Among all, 3xTg-AD female mice survivors had increased CBF in cortex and hippocampus as compared with their wildtype counterparts. Here, we also report, for the first time, asymmetry between left -right hemispheres in the female’s cortex, in the hippocampus of control males and 3xTg-AD females, as well as in the striatum of control females. Cortex was the area that better correlated with behavior, with asymmetry being associated with worse memory performance. Moreover, hemisphere CBF asymmetry in limbic system was related with copying-with-stress strategies and associated locomotor activity in anxiety tests. The present study suggests a potential compensatory hemodynamic mechanism in end-of-life dementia which is sex- and brain region dependent and can be target for pharmacological and non-pharmacological interventions.

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