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

Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in older adults

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a ‘task–rest’ paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emotional videos. Experiment 1 (N = 55) validated the task in young and older participants and unveiled age-dependent effects on brain activity and connectivity that predominated in resting periods after (rather than during) negative social scenes. Crucially, emotional elicitation potentiated subsequent resting-state connectivity between default mode network and amygdala exclusively in older adults. Experiment 2 replicated these results in a large older adult cohort (N = 127) and additionally showed that emotion-driven changes in posterior default mode network–amygdala connectivity were associated with anxiety, rumination and negative thoughts. These findings uncover the neural dynamics of empathy-related functions in older adults and help understand its relationship to poor social stress recovery

The underlying mechanisms of verbal fluency deficit in frontotemporal dementia and semantic dementia

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Quali-quantitative assessment of self-reported cognitive difficulties in non-demented elders: association with medical help seeking, cognitive deficits and beta-amyloid imaging

International audienceINTRODUCTION:Subjective cognitive decline (SCD) could help identify early stages of Alzheimer's disease. However, SCD is multidetermined and protean, and the type of cognitive complaint associated with preclinical Alzheimer's disease needs refinement.METHODS:A total of 185 nondemented elders recruited from either the community or from a memory clinic filled a questionnaire. We searched for item responses associated with medical help seeking, cognitive deficits, and β-amyloidosis.RESULTS:Compared with community-recruited control subjects (n = 74), help-seeking patients reported a stronger multidomain SCD that was mostly unrelated to the presence of detectable cognitive deficits. Only a few items, notably assessing temporal disorientation, distinguished help-seeking patients with (n = 78) or without (n = 33) memory deficits. Associations between SCD and β-amyloidosis were not restricted to the memory domain and varied across clinical stages.DISCUSSION:Detailed evaluation of SCD could provide accessible indication of the presence of β-amyloid or cognitive deficits, which might prove useful for early diagnosis and clinical trial enrichment strategies

Interaction between years of education and APOE 4 status on frontal and temporal metabolism

International audienceABSTRACT: Objective: To examine interactions between years of education and APOE ε4 status on gray matter volume and metabolism in cognitively healthy subjects.Methods: Seventy-two healthy subjects (28 APOE ε4 carriers and 44 non-carriers; from 23 to 84 years of age) with FDG-PET and structural MRI were included. A subgroup also underwent florbetapir-PET. We tested the interaction effect between years of education and APOE ε4 status (carrier vs. non-carrier) on FDG-PET and structural MRI within the whole brain (voxel-wise) adjusting for age and sex. Computed florbetapir SUVr values were used for complementary analyses.Results: We found an interaction between years of education and APOE ε4 status on fronto-temporal FDG-PET metabolism, such that higher education was positively related to fronto-temporal metabolism only in APOE ε4 carriers. Complementary analyses revealed that: i) this interaction was independent from amyloid load; ii) increased metabolism in APOE ε4 carriers in this region correlated with episodic memory performances; iii) lower educated APOE ε4 carriers showed decreased metabolism relative to non-carriers in medial temporal and prefrontal areas, while higher educated carriers were comparable to non-carriers in these areas and showed increased metabolism in the middle temporal lobe.Conclusions: Our results showed that an environmental factor such as education may counteract the effects of APOE ε4 on metabolism independently of amyloid deposition. Higher metabolism in higher (compared to lower) educated APOE ε4 carriers was found in regions that sustain episodic memory. Overall, our results point to education as a protective factor that may help to postpone cognitive changes in APOE ε4 carriers

Relationships between sleep quality and brain volume, metabolism and amyloid deposition in late adulthood.

International audienceRecent studies in mouse models of Alzheimer’s disease (AD) and in humans suggest that sleep disruption and amyloid-beta (Aβ) accumulation are interrelated, and may thus exacerbate each other. We investigated the association between self-reported sleep variables and neuroimaging data in 51 healthy older adults. Participants completed a questionnaire assessing sleep quality and quantity, and underwent positron emission tomography scans using [18F]florbetapir and [18F]fluorodeoxyglucose, and an MRI scan to measure Aβ burden, hypometabolism, and atrophy, respectively. Longer sleep latency was associated with greater Aβ burden in prefrontal areas. Moreover, the number of nocturnal awakenings was negatively correlated with gray matter volume in the insular region. In asymptomatic middle-aged and older adults, lower self-reported sleep quality was associated with greater Aβ burden and lower volume in brain areas relevant in ageing and AD, but not with glucose metabolism. These results highlight the potential relevance of preserving sleep quality in older adults, and suggest that sleep may be a factor to screen for in individuals at risk for AD

Neural correlates of Self-Reference Effect in early Alzheimer’s disease

International audienceInformation that is processed with reference to the self (i.e., self-referential processing, SRP) is generally associated with better remembering than information processed in a semantic condition. This benefit of self on memory performance is called self-reference effect (SRE). In the present study, we assessed changes in the SRE and SRP-related brain activity in patients diagnosed with mild cognitive impairment or early Alzheimer’s disease (MCI/AD). Fifteen patients with confirmed amyloid-β deposits (positive florbetapir-PET scan) and 28 healthy controls (negative florbetapir-PET scan) were included. Participants either had to judge personality trait adjectives with reference to themselves (self condition) or to a celebrity (other condition), or determine whether these adjectives were positive or not (semantic condition). These adjectives were then presented with distractors in a surprise recognition task. Functional MRI data were acquired during both the judgment and recognition tasks. The SRE, was observed in controls, but reduced in patients. Both controls and patients activated cortical midline structures when judging items with reference to themselves, but patients exhibited reduced activity in the angular gyrus. In patients, activity at encoding in the angular gyrus positively correlated with subsequent recognition accuracy in the self condition (self accuracy). This region also exhibited significant hypometabolism and Aβ burden, both related to self accuracy. By contrast, there were no differences in brain activity during recognition, either between the self and semantic conditions, or between groups. These results highlight SRE impairment in patients with MCI/AD, despite intact activity in cortical midline structures, and suggest that dysfunction of the angular gyrus is related to this impairment