Joana B Pereira1, Sara Hall2, Mattis Jalakas3, Michel J Grothe4, Olof Strandberg3, Erik Stomrud3, Eric Westman5, Danielle van Westen2, Oskar Hansson6. 1. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden. Electronic address: joana.pereira@ki.se. 2. Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden; Memory Clinic, Skåne University Hospital, Malmo, Sweden. 3. Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden. 4. German Center for Neurodegenerative Diseases (DZNE) - Rostock/Greifswald, Rostock, Germany; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. 5. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden. 6. Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden; Memory Clinic, Skåne University Hospital, Malmo, Sweden. Electronic address: Oskar.Hansson@med.lu.se.
Abstract
OBJECTIVES: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. METHODS: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. RESULTS: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). CONCLUSIONS: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
OBJECTIVES: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. METHODS: We included 106 non-demented PDpatients, 19 PDdementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PDpatients were diagnosed with dementia (PD-dementia converters), whereas the rest of PDpatients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. RESULTS: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). CONCLUSIONS:Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
Authors: Dag Aarsland; Lucia Batzu; Glenda M Halliday; Gert J Geurtsen; Clive Ballard; K Ray Chaudhuri; Daniel Weintraub Journal: Nat Rev Dis Primers Date: 2021-07-01 Impact factor: 52.329
Authors: Christine Daniels; Frank Steigerwald; Philipp Capetian; Cordula Matthies; Uwe Malzahn; Peter U Heuschmann; Jens Volkmann Journal: Neurol Res Pract Date: 2020-10-19
Authors: Sophia Rogozinski; Martin Klietz; Gesine Respondek; Wolfgang H Oertel; Michel J Grothe; Joana B Pereira; Günter U Höglinger Journal: Front Aging Neurosci Date: 2022-04-01 Impact factor: 5.702
Authors: Nicola J Ray; Lynn Rochester; Joanna Wilson; Alison J Yarnall; Chesney E Craig; Brook Galna; Sue Lord; Rosie Morris; Rachael A Lawson; Lisa Alcock; Gordon W Duncan; Tien K Khoo; John T O'Brien; David J Burn; John-Paul Taylor Journal: Mov Disord Date: 2020-12-31 Impact factor: 10.338