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Authors: Schild, Ann-Katrin | Volk, Jenny | Scharfenberg, Daniel | Schuermann, Katrin | Meiberth, Dix | Onur, Oezguer A. | Jessen, Frank | Maier, Franziska

Article Type: Research Article

Abstract: Background: Social cognition (SC) is a core criterion for neurocognitive disorders. However, findings in patients with amnestic mild cognitive impairment (aMCI) and dementia of the Alzheimer type (DAT) are inconsistent. Objective: We report assessments of emotion recognition (ER), affective and cognitive theory of mind (ToM) in young (YC) and older controls (OC) compared to aMCI and DAT. Methods: 28 aMCI, 30 DAT, 30 YC, and 29 OC received tests of SC and a comprehensive neuropsychological assessment. Analysis of covariance was used to determine group differences. Multiple regression models were applied to identify predictors for each SC task. Results: In controls, …OC performed worse in ER and both ToM tasks compared to YC except for one subtest. No significant differences were found between OC and patients concerning ER and affective ToM. In cognitive ToM, differences between OC and patients depended on content and cognitive load with significant impairment in DAT compared to OC. A cognitive composite score predicted SC in OC, but not in patients. Associations of SC with single cognitive domains were found in all groups with language and complex attention as best predictors. Not all variance of SC performance was explained by variance in cognitive domains. Conclusion: Lower performance on SC tasks in OC versus YC was confirmed, although not all tasks were equally affected. With progressive cognitive impairment, cognitive ToM is more impaired than ER or affective ToM. SC seems to be at least partly independent of other cognitive domains, justifying its inclusion in batteries for dementia diagnostic. Show more

Keywords: Amnestic mild cognitive impairment, dementia of the Alzheimer type, emotion recognition, social cognition, theory of mind

DOI: 10.3233/JAD-201126

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1173-1186, 2021

Authors: Wolfsgruber, Steffen | Kleineidam, Luca | Weyrauch, Anne-Sophie | Barkhoff, Miriam | Röske, Sandra | Peters, Oliver | Preis, Lukas | Gref, Daria | Spruth, Eike Jakob | Altenstein, Slawek | Priller, Josef | Fließbach, Klaus | Schneider, Anja | Wiltfang, Jens | Bartels, Claudia | Jessen, Frank | Maier, Franziska | Düzel, Emrah | Metzger, Coraline | Glanz, Wenzel | Buerger, Katharina | Janowitz, Daniel | Perneczky, Robert | Rauchmann, Boris-Stephan | Kilimann, Ingo | Teipel, Stefan | Laske, Christoph | Munk, Matthias H. | Roy, Nina | Spottke, Annika | Ramirez, Alfredo | Heneka, Michael T. | Brosseron, Frederic | Wagner, Michael | on behalf of the DELCODE study group

Article Type: Research Article

Abstract: Background: It is unclear whether subjective cognitive decline (SCD) is a relevant clinical marker of incipient Alzheimer’s disease (AD) and future cognitive deterioration in individuals with a family history of AD (FHAD). Objective: To investigate the association of SCD with cross-sectional cerebrospinal fluid (CSF) AD biomarker levels and cognitive decline in cognitively normal older adults with or without a first-degree FHAD. Methods: We analyzed data from cognitively normal individuals with first-degree FHAD (n  = 82 “AD relatives”; mean age: 65.7 years (SD = 4.47); 59% female) and a similar group of n  =  236 healthy controls without FHAD from the DELCODE study. We …measured SCD with an in-depth structured interview from which we derived a SCD score, capturing features proposed to increase likelihood of underlying AD (“SCD-plus score”). We tested whether higher SCD-plus scores were associated with more pathological CSF AD biomarker levels and cognitive decline over time and whether this association varied by group. Results: AD relatives showed higher SCD-plus scores than healthy controls and more cognitive decline over time. Higher SCD-plus scores also related stronger to cognitive change and abnormal CSF AD biomarker levels in the AD relatives as compared to the healthy controls group. Conclusion: Quantification of specific SCD features can provide further information on the likelihood of early AD pathology and cognitive decline among AD relatives. FHAD and SCD appear as synergistically acting enrichment strategies in AD research, the first one as a permanent indicator of genetic risk, the latter one as a correlate of disease progression. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, family history, subjective cognitive decline

DOI: 10.3233/JAD-215416

Citation: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 545-555, 2022

Authors: Teipel, Stefan J. | Dyrba, Martin | Ballarini, Tommaso | Brosseron, Frederic | Bruno, Davide | Buerger, Katharina | Cosma, Nicoleta-Carmen | Dechent, Peter | Dobisch, Laura | Düzel, Emrah | Ewers, Michael | Fliessbach, Klaus | Haynes, John D. | Janowitz, Daniel | Kilimann, Ingo | Laske, Christoph | Maier, Franziska | Metzger, Coraline D. | Munk, Matthias H. | Peters, Oliver | Pomara, Nunzio | Preis, Lukas | Priller, Josef | Ramírez, Alfredo | Roy, Nina | Scheffler, Klaus | Schneider, Anja | Schott, Björn H. | Spottke, Annika | Spruth, Eike J. | Wagner, Michael | Wiltfang, Jens | Jessen, Frank | Heneka, Michael T.

Article Type: Research Article

Abstract: Background: Inflammation has been described as a key pathogenic event in Alzheimer’s disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. Methods: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume …and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aβ42 /ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, cholinergic system, neuroinflammation, MRI, plasma, sTREM2

DOI: 10.3233/JAD-215196

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1267-1282, 2022

Authors: Ersoezlue, Ersin | Perneczky, Robert | Tato, Maia | Utecht, Julia | Kurz, Carolin | Häckert, Jan | Guersel, Selim | Burow, Lena | Koller, Gabriele | Stoecklein, Sophia | Keeser, Daniel | Papazov, Boris | Totzke, Marie | Ballarini, Tommaso | Brosseron, Frederic | Buerger, Katharina | Dechent, Peter | Dobisch, Laura | Ewers, Michael | Fliessbach, Klaus | Glanz, Wenzel | Haynes, John Dylan | Heneka, Michael T. | Janowitz, Daniel | Kilimann, Ingo | Kleineidam, Luca | Laske, Christoph | Maier, Franziska | Munk, Matthias H. | Peters, Oliver | Priller, Josef | Ramirez, Alfredo | Roeske, Sandra | Roy, Nina | Scheffler, Klaus | Schneider, Anja | Schott, Björn H. | Spottke, Annika | Spruth, Eike J. | Teipel, Stefan | Unterfeld, Chantal | Wagner, Michael | Wang, Xiao | Wiltfang, Jens | Wolfsgruber, Steffen | Yakupov, Renat | Duezel, Emrah | Jessen, Frank | Rauchmann, Boris-Stephan

Article Type: Research Article

Abstract: Background: Cognitive reserve (CR) explains inter-individual differences in the impact of the neurodegenerative burden on cognitive functioning. A residual model was proposed to estimate CR more accurately than previous measures. However, associations between residual CR markers (CRM) and functional connectivity (FC) remain unexplored. Objective: To explore the associations between the CRM and intrinsic network connectivity (INC) in resting-state networks along the neuropathological-continuum of Alzheimer’s disease (ADN). Methods: Three hundred eighteen participants from the DELCODE cohort were stratified using cerebrospinal fluid biomarkers according to the A(myloid-β)/T(au)/N(eurodegeneration) classification. CRM was calculated utilizing residuals obtained from a multilinear regression model predicting cognition from …markers of disease burden. Using an independent component analysis in resting-state fMRI data, we measured INC of resting-state networks, i.e., default mode network (DMN), frontoparietal network (FPN), salience network (SAL), and dorsal attention network. The associations of INC with a composite memory score and CRM and the associations of CRM with the seed-to-voxel functional connectivity of memory-related were tested in general linear models. Results: CRM was positively associated with INC in the DMN in the entire cohort. The A+T+N+ group revealed an anti-correlation between the SAL and the DMN. Furthermore, CRM was positively associated with anti-correlation between memory-related regions in FPN and DMN in ADN and A+T/N+. Conclusion: Our results provide evidence that INC is associated with CRM in ADN defined as participants with amyloid pathology with or without cognitive symptoms, suggesting that the neural correlates of CR are mirrored in network FC in resting-state. Show more

Keywords: Alzheimer’s disease, cognition, cognitive reserve, functional MRI, intrinsic network connectivity, resting-state functional connectivity

DOI: 10.3233/JAD-220464

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 925-940, 2023

Authors: Rauchmann, Boris-Stephan | Gross, Patrizia | Ersoezlue, Ersin | Wagner, Michael | Ballarini, Tommaso | Kurz, Carolin | Tatò, Maia | Utecht, Julia | Papazov, Boris | Guersel, Selim | Totzke, Marie | Trappmann, Lena | Burow, Lena | Koller, Gabriele | Stöcklein, Sophia | Keeser, Daniel | Altenstein, Slawek | Bartels, Claudia | Buerger, Katharina | Dechent, Peter | Dobisch, Laura | Ewers, Michael | Fliessbach, Klaus | Freiesleben, Silka Dawn | Glanz, Wenzel | Goeerss, Doreen | Gref, Daria | Haynes, John Dylan | Janowitz, Daniel | Kilimann, Ingo | Kimmich, Okka | Kleineidam, Luca | Laske, Christoph | Lohse, Andrea | Maier, Franziska | Metzger, Coraline D. | Munk, Matthias H. | Peters, Oliver | Preis, Lukas | Priller, Josef | Roeske, Sandra | Roy, Nina | Sanzenbacher, Carolin | Scheffler, Klaus | Schneider, Anja | Schott, Björn Hendrik | Spottke, Annika | Spruth, Eike Jakob | Teipel, Stefan | van Lent, Debora Melo | Wiltfang, Jens | Wolfsgruber, Steffen | Yakupov, Renat | Düzel, Emrah | Jessen, Frank | Perneczky, Robert

Article Type: Research Article

Abstract: BACKGROUND: There is evidence that adherence to Mediterranean-like diet reduces cognitive decline and brain atrophy in Alzheimer's disease (AD). However, lengthy dietary assessments, such as food frequency questionnaires (FFQs), discourage more frequent use. OBJECTIVE: Here we aimed to validate a 6-items short questionnaire for a Mediterranean-like diet (6-QMD) and explore its associations with memory performance and hippocampal atrophy in healthy elders and individuals at risk for AD. METHODS: We analyzed 938 participants (N = 234 healthy controls and N = 704 participants with an increased AD risk) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). The 6-QMD was validated against the Mediterranean Diet …(MeDi) score and the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) score, both derived from a detailed FFQ. Furthermore, associations between the 6-QMD and memory function as well as hippocampal atrophy were evaluated using linear regressions. RESULTS: The 6-QMD was moderately associated with the FFQ-derived MeDi adherence score (ρ = 0.25, p  < 0.001) and the MIND score (ρ = 0.37, p = < 0.001). Higher fish and olive oil consumption and lower meat and sausage consumption showed significant associations in a linear regression, adjusted for diagnosis, age, sex and education, with memory function (β = 0.1, p  = 0.008) and bilateral hippocampal volumes (left: β = 0.15, p  < 0.001); (right: β = 0.18, p  < 0.001)). CONCLUSIONS: The 6-QMD is a useful and valid brief tool to assess the adherence to MeDi and MIND diets, capturing associations with memory function and brain atrophy in healthy elders and individuals at increased AD dementia risk, making it a valid alternative in settings with time constraints. Show more

DOI: 10.3233/NHA-220190

Citation: Nutrition and Healthy Aging, vol. 8, no. 1, pp. 143-156, 2023