When Higher Activations Reflect Lower Deactivations: A PET Study in Alzheimer’s Disease during Encoding and Retrieval in Episodic Memory

The aim of the present study was to explore the cerebral substrates of episodic memory disorders in Alzheimer’s disease (AD) and investigate patients’ hyperactivations frequently reported in the functional imaging literature. It remains unclear whether some of these hyperactivations reflect real increased activity or deactivation disturbances in the default mode network (DMN). Using positron emission tomography (15O-H2O), cerebral blood flow was measured in 11 AD patients and 12 healthy elderly controls at rest and during encoding and stem-cued recall of verbal items. Subtractions analyses between the target and control conditions were performed and compared between groups. The average signal was extracted in regions showing hyperactivation in AD patients versus controls in both contrasts. To determine whether hyperactivations occurred in regions that were activated or deactivated during the memory tasks, we compared signal intensities between the target conditions versus rest. Our results showed reduced activation in AD patients compared to controls in several core episodic memory regions, including the medial temporal structures, during both encoding and retrieval. Patients also showed hyperactivations compared to controls in a set of brain areas. Further analyses conducted on the signal extracted in these areas indicated that most of these hyperactivations actually reflected a failure of deactivation. Indeed, whereas almost all of these regions were significantly more activated at rest than during the target conditions in controls, only one region presented a similar pattern of deactivation in patients. Altogether, our findings suggest that hyperactivations in AD must be interpreted with caution and may not systematically reflect increased activity. Although there has been evidence supporting the existence of genuine compensatory mechanisms, dysfunction within the DMN may be responsible for part of the apparent hyperactivations reported in the literature on AD

Depressive Symptoms Have Distinct Relationships With Neuroimaging Biomarkers Across the Alzheimer's Clinical Continuum

Background: Depressive and anxiety symptoms are frequent in Alzheimer’s disease and associated with increased risk of developing Alzheimer’s disease in older adults. We sought to examine their relationships to Alzheimer’s disease biomarkers across the preclinical and clinical stages of the disease. Method: Fifty-six healthy controls, 35 patients with subjective cognitive decline and 56 amyloid-positive cognitively impaired patients on the Alzheimer’s continuum completed depression and anxiety questionnaires, neuropsychological tests and neuroimaging assessments. We performed multiple regressions in each group separately to assess within group associations of depressive and anxiety symptoms with either cognition (global cognition and episodic memory) or neuroimaging data (gray matter volume, glucose metabolism and amyloid load). Results: Depressive symptoms, but not anxiety, were higher in patients with subjective cognitive decline and cognitively impaired patients on the Alzheimer’s continuum compared to healthy controls. Greater depressive symptoms were associated with higher amyloid load in subjective cognitive decline patients, while they were related to higher cognition and glucose metabolism, and to better awareness of cognitive difficulties, in cognitively impaired patients on the Alzheimer’s continuum. In contrast, anxiety symptoms were not associated with brain integrity in any group. Conclusion: These data show that more depressive symptoms are associated with greater Alzheimer’s disease biomarkers in subjective cognitive decline patients, while they reflect better cognitive deficit awareness in cognitively impaired patients on the Alzheimer’s continuum. Our findings highlight the relevance of assessing and treating depressive symptoms in the preclinical stages of Alzheimer’s disease

Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer's disease.

International audienceA sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression

Distinct relationships of self-reported subjective memory decline to neurodegeneration across the Alzheimer's clinical continuum: Neuroimaging/Optimal neuroimaging measures for tracking disease progression

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Effect of cognitive reserve on the association between slow wave sleep and cognition in community-dwelling older adults

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition

IC-P-082: ASSOCIATION OF PERCEIVED MEMORY DECLINE WITH MULTIMODAL NEUROIMAGING AT DIFFERENT STAGES OF ALZHEIMER'S DISEASE

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White matter hyperintensities in Alzheimer’s disease: Topography of lesions and association with cognition: Neuroimaging/differential diagnosis

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P3-381: IMPACT OF THE RECRUITMENT SETTING ON THE CHARACTERISTICS OF PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE

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Recognition-based memory through familiarity assessment in severe Alzheimer’s disease

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Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time

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