One of the most common nonmotor symptoms in Parkinson disease (PD) is the co-occurrence of dementia, with a mean prevalence of 30%.¹ Dementia in PD is an important cause for nursing home placement,² caregiver distress,³ higher health care burden,⁴ and increased mortality.⁵ The combination of dementia and parkinsonism is also a key feature that characterizes dementia with Lewy bodies (LBD), the second most common cause of neurodegenerative dementia in the elderly after Alzheimer disease (AD). A recent genome-wide association study has provided unequivocal evidence for a genetic association of the microtubule-associated protein tau (MAPT) (GenBank NG_007398.1 and OMIM 157140) locus with PD in the population with European origin.⁶ However, these results were not replicated in an independent genome-wide association study performed in an Asian population.⁷ With up to 21 studies performed to date, MAPT seems to be undoubtedly associated with PD risk (http://www.pdgene.org). In particular, the MAPT H1 variant, an extended haplotype that results from a common genomic inversion of approximately 800 kb in chromosome 17q21 containing the MAPT gene, has been found to be related to PD risk.^8-14 Interestingly, the H1 variant has also been associated with cognitive decline in a longitudinal study of PD with a 3½-year follow-up.⁹ In a subsequent study by some of the same authors, the MAPT H1 allele was the strongest independent predictor of dementia among PD patients, with an odds ratio (OR) of 12.1 during 5 years of follow-up.¹⁵ Research addressing the effect of MAPT in other neurodegenerative disorders, such as AD, has yielded inconclusive results.^16-19 A fine-mapping study of the MAPT H1/H2 clades described the H1c subhaplotype, a version of the H1 haplotype, to be the specific variant associated with AD risk.¹⁸ However, this association has been inconsistently found in subsequent studies.^20,21 The specific MAPT subhaplotype linked to PD, Parkinson disease–dementia (PDD) complex, or LBD remains unknown.

Dementia is a frequent and devastating complication in Parkinson’s disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients. We aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer. In a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex. The pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing.