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Research paper
Hippocampal subfield atrophy of CA1 and subicular structures predict progression to dementia in idiopathic Parkinson’s disease
  1. Audrey Low1,
  2. Heidi Foo1,
  3. Ting Ting Yong1,
  4. Louis C S Tan1,2,
  5. Nagaendran Kandiah1,2
  1. 1 Department of Neurology, National Neuroscience Institute, Singapore, Singapore
  2. 2 Duke-NUS Medical School, Singapore, Singapore
  1. Correspondence to Dr Nagaendran Kandiah, Department of Neurology, National Neuroscience Institute, Singapore 308433, Singapore; nagaendran_kandiah{at}


Background Global hippocampal atrophy is a hallmark of Alzheimer’s dementia and has been similarly reported in Parkinson’s disease dementia (PDD). However, there is limited literature on the differential involvement of hippocampal subfields in predicting conversion to PDD. This study is an extension of previous findings on progression to mild cognitive impairment in Parkinson’s disease (PD).

Methods This cohort study recruited 73 non-demented participants with idiopathic PD (age 65.80±8.17, 75.3% male) from an outpatient neurology clinic. All participants underwent clinical assessment, neuropsychological testing and 3T MRI scans at baseline and 18 months while on prescribed dopaminergic medication. Hippocampal subfield volumes were obtained using automatic segmentation in FreeSurfer V.6.0. Participants who progressed to PDD and those who did not were compared on hippocampal subfield atrophy and cognitive change (episodic memory, attention, executive functions, language, visuospatial abilities). Subfields were further examined for their abilities to predict PDD conversion and distinguish PDD from non-demented PD using receiver operating characteristic analysis.

Results Smaller baseline global hippocampal volume, cornu ammonis (CA) subfield CA1, subiculum and presubiculum volumes were observed in participants who went on to develop dementia, and predicted PDD conversion. Those who progressed to PDD saw greater decline in global hippocampal volume, granule cell layer of the dentate gyrus, presubiculum, parasubiculum and fimbria. Decline in subiculum and fimbria volume corresponded to cognitive decline in attention and executive functions, respectively.

Conclusions Early atrophy of CA1, subiculum and presubiculum preceded, and predicted, PDD conversion. Differential patterns of subfield atrophy were also observed among those who progressed to PDD and were associated with impaired executive functions.

  • parkinson’s disease dementia
  • cognitive impairment
  • neuroimaging
  • hippocampus

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  • Contributors AL contributed to study design, statistical analysis, interpretation of data, and drafting and revision of the manuscript for intellectual content. HF contributed to study design, analysis, and drafting, revision and final approval of the manuscript. TTY contributed to data collection, statistical analysis and revision of the manuscript for intellectual content. LCST contributed to interpretation of data, and revision and final approval of the manuscript. NK contributed to study design, interpretation of data, and revision and final approval of the manuscript.

  • Funding The research was supported by the National Neuroscience Institute (Singapore) in the design and conduct of the study. This study was funded by the National Medical Research Council (NMRC/CSA/0063/2014).

  • Competing interests AL, HF and TTY report no disclosures. LCST has received research support from Singapore Millennium Foundation and funding for conference travel from GlaxoSmithKline. NK has received CME sponsorship from Lundbeck, Novartis, Pfizer and Eisai, and research funding from the SingHealth Foundation and the National Medical Research Council of Singapore.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the SingHealth Institutional Ethics Review Board, and informed consent was obtained from all participants prior to data collection.

  • Provenance and peer review Not commissioned; externally peer reviewed.