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We aimed to characterise these patterns using\n                      <jats:sup>123<\/jats:sup>\n                      I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (\u03b14\u03b22 nAChR assessment) and examine their association with cognitive function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifteen DLB and 16 healthy controls underwent\n                      <jats:sup>123<\/jats:sup>\n                      5IA-85380 and rCBF\n                      <jats:sup>99m<\/jats:sup>\n                      Tc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified \u03b14\u03b22 nAChR and rCBF patterns distinguishing DLB from controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A distinct \u03b14\u03b22 nAChR pattern differentiated DLB from controls (F\n                      <jats:sub>1,29<\/jats:sub>\n                      \u2009=\u2009165.1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior\/mid cingulate, and putamen, alongside preserved\/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. We then derived from patients, \u03b14\u03b22 nAChR patterns that correlated with CAMCOG\n                      <jats:sub>total<\/jats:sub>\n                      (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2013\u20090.52,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04), MMSE (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2013\u20090.68,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) and CAMCOG\n                      <jats:sub>memory<\/jats:sub>\n                      (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2013\u20090.70,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), demonstrating a common topography of relative decreased binding in lateral\/medial prefrontal, lateral temporal, fusiform, inferior parietal and thalamus along with relative preserved\/increased binding in cingulate, insula, occipital and medial temporal regions: structures within a range of networks supporting executive, language, attention, motor and visual processing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings provide novel insights into the pathophysiology of DLB and may inform future therapeutic strategies targeting nAChRs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-13332-5","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:34:30Z","timestamp":1759134870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A spatial covariance 123I-5IA-85380 SPECT study of \u03b14\u03b22 nicotinic receptors in dementia with Lewy bodies"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5775-2524","authenticated-orcid":false,"given":"Judith R.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean J.","family":"Colloby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John-Paul","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"13332_CR1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1136\/jnnp.74.9.1215","volume":"74","author":"D Aarsland","year":"2003","unstructured":"Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP (2003) Performance on the dementia rating scale in Parkinson\u2019s disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer\u2019s disease. 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Dr Colloby reports no disclosures. Professor O\u2019Brien has acted as a consultant for TauRx, Novo Nordisk, Biogen, Roche, Lilly, GE Healthcare and Okwin and received grants or academic in kind support from Avid\/Lilly, Merck, UCB and Alliance Medical. Professor Taylor has received honoraria for talks from GE Healthcare and consulted for CervoMed and Eisai.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the Newcastle, North Tyneside and Northumberland local research ethics committee and the UK Department of Health\u2019s Administration of Radioactive Substances Advisory Committee (ARSAC).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All participants and\/or nearest relative (for patients who lacked capacity) gave informed written consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"660"}}