VAMP2 is a cerebrospinal fluid marker of selective hippocampal synapse loss and episodic memory performance in Alzheimer’s disease

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.

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Association of neuroinflammation with episodic memory: a [11C]PBR28 PET study in cognitively discordant twin pairs

Brain Communications ◽

10.1093/braincomms/fcaa024 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Noora Lindgren ◽

Jouni Tuisku ◽

Eero Vuoksimaa ◽

Semi Helin ◽

Mira Karrasch ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Episodic Memory ◽

Memory Performance ◽

Disease Process ◽

Standardized Uptake Value ◽

Weighted Average ◽

Translocator Protein ◽

Interindividual Variation ◽

Protein Genotype

Abstract Alzheimer’s disease is associated with chronic response of innate immune system, referred as neuroinflammation. PET radioligands binding to the 18 kDa translocator protein are potential biomarkers of neuroinflammation. Translocator protein PET studies in mild cognitive impairment and Alzheimer’s disease have indicated controversial results, possibly reflecting interindividual variation and heterogeneity of study populations. We controlled for genetic and environmental effects by studying twin pairs discordant for episodic memory performance. Episodic memory impairment is a well-known cognitive hallmark of early Alzheimer’s disease process. Eleven same-sex twin pairs (four monozygotic pairs, six female pairs, age 72–77 years) underwent [11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28) PET imaging, structural magnetic resonance imaging and neuropsychological testing in 2014–17. Main PET outcome was the volume-weighted average standardized uptake value of cortical regions vulnerable to Alzheimer’s disease pathology. Ten pairs were discordant for episodic memory performance. In the eight pairs with identical translocator protein genotype, twins with poorer episodic memory had ∼20% higher cortical [11C]PBR28 binding compared with their better-performing co-twins (mean intra-pair difference 0.21 standardized uptake value, 95% confidence interval 0.05–0.37, P = 0.017). The result remained the same when including all discordant pairs and controlling for translocator protein genotype. Increased translocator protein PET signal suggests that increased microglial activation is associated with poorer episodic memory performance. Twins with worse episodic memory performance compared with their co-twins had on average 20% higher uptake of the neuroinflammatory marker translocator protein PET tracer 11[11C]PBR28. The findings support a negative association between neuroinflammation and episodic memory and the use of translocator protein positron emission tomography as a useful indicator of Alzheimer’s disease process.

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Which Episodic Memory Performance is Associated with Alzheimer’s Disease Biomarkers in Elderly Cognitive Complainers? Evidence from a Longitudinal Observational Study with Four Episodic Memory Tests (Insight-PreAD)

Journal of Alzheimer s Disease ◽

10.3233/jad-180966 ◽

2019 ◽

Vol 70 (3) ◽

pp. 811-824 ◽

Cited By ~ 4

Author(s):

Geoffroy Gagliardi ◽

Stéphane Epelbaum ◽

Marion Houot ◽

Hovagim Bakardjian ◽

Laurie Boukadida ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Observational Study ◽

Episodic Memory ◽

Memory Performance ◽

Memory Tests ◽

Disease Biomarkers ◽

Longitudinal Observational Study

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APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

10.1101/2019.12.11.871681 ◽

2019 ◽

Author(s):

Sheida Rabipour ◽

Sricharana Rajagopal ◽

Elsa Yu ◽

Stamatoula Pasvanis ◽

John Breitner ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Episodic Memory ◽

Brain Activity ◽

Memory Performance ◽

Group Differences ◽

Parental History ◽

History Of ◽

Spatial Source

AbstractEpisodic memory decline is one of the earliest symptoms of late-onset Alzheimer’s Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent’s conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory. Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network. However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.

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Association of glial and neuronal degeneration markers with Alzheimer‘s disease cerebrospinal fluid profile and cognitive functions

10.21203/rs.2.19886/v1 ◽

2020 ◽

Author(s):

Unnur D. Teitsdottir ◽

Maria K. Jonsdottir ◽

Sigrun H. Lund ◽

Taher Darreh-Shori ◽

Jon Snaedal ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Episodic Memory ◽

Processing Speed ◽

Cognitive Functions ◽

Neuronal Degeneration ◽

Enzyme Linked Immunosorbent Assay ◽

Cognitive Domains ◽

Verbal Episodic Memory

Abstract Background Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer‘s disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages.Methods In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having CSF AD (n=28, age=67, 33% female, Mini-mental state examination [MMSE]=28) or non-AD (n=24, age=70, 39% female, MMSE=27) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β 1‐42 (Aβ 42 ) values (cut-off point chosen as 0.52). Novel CSF biomarkers included Neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and Glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assay (ELISA). Subjects underwent a neuropsychological assessment for evaluation of different cognitive domains including verbal episodic memory, non-verbal memory, language, processing speed and executive functions.Results Accuracy for distinguishing between the two CSF profiles was calculated for each CSF marker and cognitive domain. Verbal episodic memory performed the best overall (Area under curve [AUC]=0.80), with AUCs for CSF markers ranging from 0.61 to 0.64. For estimation of the relationships between CSF markers and cognitive domains (adjusted for age and education), Pearson‘s correlation and ridge regression analyses were performed. The ratio between NFL and YKL-40 levels correlated higher with verbal episodic memory score (r=-0.51, p <0.001) compared to single protein levels (NFL: r=-0.26, p =0.06; YKL-40: r=0.18, p =0.20). The correlation was also higher among those with CSF AD profile (r=-0.67, p <0.001) compared to those without (r=-0.46, p =0.03). GFAP levels showed weak correlation with executive functions scores (r=-0.37, p =0.007). Among those with a CSF AD profile, both S100B (r=-0.45, p =0.02) and GFAP (0.68, p <0.001) levels correlated with processing speed scores.ConclusionsThe novel CSF markers NFL, YKL-40 and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.

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P2-066: The cerebrospinal fluid “alzheimer profile” and episodic memory in SCI, MCI, and Alzheimer's disease sample patients

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.06.603 ◽

2015 ◽

Vol 11 (7S_Part_11) ◽

pp. P508-P508

Author(s):

Monika Mandecka ◽

Barczak Anna ◽

Magda Budziszewska ◽

Maria Styczynska ◽

Maria Barcikowska ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Episodic Memory

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White matter disruption at the prodromal stage of Alzheimer's disease: Relationships with hippocampal atrophy and episodic memory performance

NeuroImage Clinical ◽

10.1016/j.nicl.2015.01.014 ◽

2015 ◽

Vol 7 ◽

pp. 482-492 ◽

Cited By ~ 43

Author(s):

Florence Rémy ◽

Nathalie Vayssière ◽

Laure Saint-Aubert ◽

Emmanuel Barbeau ◽

Jérémie Pariente

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Episodic Memory ◽

Memory Performance ◽

Hippocampal Atrophy ◽

Prodromal Stage

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

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000446425 ◽

2016 ◽

Vol 6 (2) ◽

pp. 303-312 ◽

Cited By ~ 7

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.

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