TY  - JOUR
A1  - Liebe, Thomas
A1  - Dordevic, Milos
A1  - Kaufmann, Jörn
A1  - Avetisyan, Araks
A1  - Skalej, Martin
A1  - Müller, Notger Germar
T1  - Investigation of the functional pathogenesis of mild cognitive impairment by localisation-based locus coeruleus resting-state fMRI
JF  - Human Brain Mapping
N2  - Dementia as one of the most prevalent diseases urges for a better understanding of the central mechanisms responsible for clinical symptoms, and necessitates improvement of actual diagnostic capabilities. The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation-based LC resting-state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, n = 28) and an age-matched healthy control group (n = 29). MCI and control participants could be differentiated in their Mini-Mental-State-Examination (MMSE) scores (p < .001) and LC intensity ratio (p = .010). In the fMRI, LC fc to anterior cingulate cortex (FDR p < .001) and left anterior insula (FDR p = .012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR p = .012) and posterior cingulate cortex (PCC, FDR p = .021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (p = .017). Furthermore, we found a hyperactivation of the left-insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression.
KW  - attention
KW  - locus coeruleus
KW  - mild cognitive impairment
KW  - resting-state fMRI
Y1  - 2022
U6  - https://doi.org/10.1002/hbm.26039
SN  - 1097-0193
VL  - 43
SP  - 5630
EP  - 5642
PB  - Wiley
CY  - New York, NY, USA
ET  - 18
ER  - 
TY  - JOUR
A1  - Stroehle, Andreas
A1  - Schmidt, Dietlinde K.
A1  - Schultz, Florian
A1  - Fricke, Nina
A1  - Staden, Theresa
A1  - Hellweg, Rainer
A1  - Priller, Josef
A1  - Rapp, Michael Armin
A1  - Rieckmann, Nina
T1  - Drug and Exercise Treatment of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Effects on Cognition in Randomized Controlled Trials
JF  - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
N2  - Objective: Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations. Methods: We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated. Results: Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients). Conclusions: Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention. Identifier: PROSPERO (2013:CRD42013003910).
KW  - Alzheimer dementia
KW  - mild cognitive impairment
KW  - drug
KW  - exercise
Y1  - 2015
U6  - https://doi.org/10.1016/j.jagp.2015.07.007
SN  - 1064-7481
SN  - 1545-7214
VL  - 23
IS  - 12
SP  - 1234
EP  - 1249
PB  - Elsevier
CY  - New York
ER  -