Prefrontal Compensatory Mechanism May Enable Normal Semantic Memory Performance in Mild Cognitive Impairment (MCI)

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s < 0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

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Lower functional hippocampal redundancy in mild cognitive impairment

Translational Psychiatry ◽

10.1038/s41398-020-01166-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stephanie Langella ◽

◽

Muhammad Usman Sadiq ◽

Peter J. Mucha ◽

Kelly S. Giovanello ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Resting State ◽

Memory Performance ◽

Potential Mechanism ◽

Network Efficiency ◽

Cognitively Normal ◽

Normal Individuals ◽

The Relationship

AbstractWith an increasing prevalence of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in response to an aging population, it is critical to identify and understand neuroprotective mechanisms against cognitive decline. One potential mechanism is redundancy: the existence of duplicate elements within a system that provide alternative functionality in case of failure. As the hippocampus is one of the earliest sites affected by AD pathology, we hypothesized that functional hippocampal redundancy is protective against cognitive decline. We compared hippocampal functional redundancy derived from resting-state functional MRI networks in cognitively normal older adults, with individuals with early and late MCI, as well as the relationship between redundancy and cognition. Posterior hippocampal redundancy was reduced between cognitively normal and MCI groups, plateauing across early and late MCI. Higher hippocampal redundancy was related to better memory performance only for cognitively normal individuals. Critically, functional hippocampal redundancy did not come at the expense of network efficiency. Our results provide support that hippocampal redundancy protects against cognitive decline in aging.

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Lexical semantic memory in amnestic mild cognitive impairment and mild Alzheimer's disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2007000400014 ◽

2007 ◽

Vol 65 (3a) ◽

pp. 619-622 ◽

Cited By ~ 13

Author(s):

Marcio L.F. Balthazar ◽

José E. Martinelli ◽

Fernando Cendes ◽

Benito P. Damasceno

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Semantic Memory ◽

Statistical Significance ◽

Verbal Learning ◽

Amnestic Mild Cognitive Impairment ◽

Memory Tests ◽

Lexical Semantic

OBJECTIVE: To study lexical semantic memory in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer's disease (AD) and normal controls. METHOD: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, and that of aMCI, on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent semantic memory tests (Boston Naming-BNT, CAMCOG Similarities item), Rey Auditory Verbal Learning Test (RAVLT), Mini-Mental Status Examination (MMSE), neuropsychological tests (counterproofs), and Cornell Scale for Depression in Dementia. Data analysis used Mann-Whitney test for intergroup comparisons and Pearson's coefficient for correlations between memory tests and counterproofs (statistical significance level was p<0.05). RESULTS: aMCI patients were similar to controls on BNT and Similarities, but worse on MMSE and RAVLT. Mild AD patients scored significantly worse than aMCI and controls on all tests. CONCLUSION: aMCI impairs episodic memory but tends to spare lexical semantic system, which can be affected in the early phase of AD.

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Memory-Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis

Journal of Alzheimer s Disease ◽

10.3233/jad-200931 ◽

2020 ◽

pp. 1-11

Author(s):

Yang Jiang ◽

Juan Li ◽

Frederick A. Schmitt ◽

Gregory A. Jicha ◽

Nancy B. Munro ◽

...

Keyword(s):

Older Adults ◽

Working Memory ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Memory Performance ◽

Memory Task ◽

Cognitive Status ◽

Older Individuals ◽

Increased Risk ◽

Differentiation Pattern

Background: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer’s disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals. Objective: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis. Methods: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed. Results: Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters’ frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters’ baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08). Conclusion: The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.

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Memory in individuals with mild cognitive impairment in relation to APOE and CSF Aβ42

International Psychogeriatrics ◽

10.1017/s1041610210000335 ◽

2010 ◽

Vol 22 (4) ◽

pp. 598-606 ◽

Cited By ~ 5

Author(s):

Valgeir Thorvaldsson ◽

Arto Nordlund ◽

Ivar Reinvang ◽

Kaj Blennow ◽

Henrik Zetterberg ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Memory Performance ◽

Interactive Effect ◽

Amyloid Β ◽

Total Sample ◽

Increased Risk ◽

Latent Curve ◽

Latent Curve Models ◽

Ε4 Allele

ABSTRACTBackground: The ε4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid β-proteins 42 (Aβ) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI).Methods: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data.Results: Analyses accounting for age, gender, education, APOE, Aβ42, and interaction between APOE and Aβ42 revealed that the ε4 allele was significantly associated with level of memory performance in the presence of low Aβ42 values (≤452 ng/L). Associations between memory performance and Aβ42 were significant among the ε4 carriers but not among the non-carriers. The Aβ42 marker was, however, significantly associated with changes in memory over the study time period in the total sample.Conclusion: The findings support the hypothesis of an interactive effect of APOE and Aβ42 for memory decline in MCI patients.

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

10.1101/2020.05.11.089383 ◽

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)

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