Early functional changes in lewy body dementia: roles of dynamics, locus coeruleus, and compensation
Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
LX22NPO5107
Czech Ministry of Education, Youth and Sports
LX22NPO5107
Czech Ministry of Education, Youth and Sports
LX22NPO5107
Czech Ministry of Education, Youth and Sports
LX22NPO5107
Czech Ministry of Education, Youth and Sports
9F25001
Ministry of Education, Youth and Sports of the CR
9F25001
Ministry of Education, Youth and Sports of the CR
9F25001
Ministry of Education, Youth and Sports of the CR
101147319
European Union's Horizon Europe research and innovation programme
101147319
European Union's Horizon Europe research and innovation programme
101147319
European Union's Horizon Europe research and innovation programme
101147319
European Union's Horizon Europe research and innovation programme
101130827
HORIZON EUROPE Marie Sklodowska-Curie Actions
PubMed
40849483
DOI
10.1186/s13195-025-01828-1
PII: 10.1186/s13195-025-01828-1
Knihovny.cz E-zdroje
- Klíčová slova
- Cognitive reserve, Dementia with lewy bodies, Dynamic functional connectivity, Fluidity, Locus coeruleus, Node strength, Prodromal dementia with lewy bodies,
- MeSH
- demence s Lewyho tělísky * patofyziologie diagnostické zobrazování psychologie MeSH
- elektroencefalografie MeSH
- kognitivní dysfunkce * patofyziologie diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- locus coeruleus * patofyziologie diagnostické zobrazování MeSH
- magnetická rezonanční tomografie MeSH
- prodromální symptomy MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Dementia with Lewy bodies (DLB) is marked by multidomain cognitive impairments, with fluctuations in cognition and alertness being among the most common clinical features. Disruptions in functional connectivity are thought to underlie these fluctuations, but it remains unclear whether such patterns are already present at prodromal stages. We investigated the presence of static and dynamic functional connectivity alterations and their contribution to the clinical phenotype of prodromal DLB, and explored their association with declining locus coeruleus integrity, while considering premorbid intelligence (a proxy for cognitive reserve) as a moderating factor. Three groups of participants on the prodromal spectrum were analyzed: 29 healthy controls, 58 cognitively normal subjects with core clinical features of prodromal DLB (CN-CCF), and 39 subjects with mild cognitive impairment due to Lewy body dementia (MCI-LB). Dynamic and static functional connectivity features were derived from resting-state source-reconstructed high-density EEG, and integrity of the right caudal locus coeruleus was quantified using neuromelanin-sensitive MRI. Robust analyses, such as PERMANOVA, Spearman correlations and general linear models were conducted to study the relationships. We observed a nonlinear trajectory of two functional connectivity metrics-temporal variability (fluidity) and connectedness (average node strength)-across symptom severity, especially in the delta frequency band. Both measures (F(2,123) = 1.86, p =.037; F(2,123) = 1.51, p =.023, respectively) were elevated in the intermediate severity groups-that is, in CN-CCF and possible MCI-LB (i.e., one core clinical feature)-and this was associated with better executive functioning after controlling for age and premorbid intelligence (rho = 0.26, p =.004; rho = 0.28, p =.002, respectively). Additionally, elevated fluidity (rho = - 0.34, p =.034) and average node strength (rho = - 0.37, p =.022) were also correlated with fewer fluctuations in alertness in subjects with MCI-LB. Fluidity was further associated with right caudal locus coeruleus integrity, particularly among individuals with lower premorbid intelligence (F(5,97) = 3.56, p =.005). Our findings indicate that increased dynamic reconfiguration and enhanced connectivity may serve compensatory functions in early DLB, helping temporarily preserve cognition. As DLB progresses, these mechanisms wane, with noradrenergic contributions more evident in individuals with lower cognitive reserve. Clinical trial number Not applicable.
Central European Institute of Technology Masaryk University Pekařská 53 Brno 65691 Czech Republic
Faculty of Medicine Masaryk University Pekařská 53 Brno 65691 Czech Republic
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