Genotype-Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review.

This first comprehensive MDSGene review is devoted to the 3 autosomal recessive Parkinson's disease forms: PARK-Parkin, PARK-PINK1, and PARK-DJ1. It followed MDSGene's standardized data extraction protocol and screened a total of 3652 citations and is based on fully curated phenotypic and genotypic data on >1100 patients with recessively inherited PD because of 221 different disease-causing mutations in Parkin, PINK1, or DJ1. All these data are also available in an easily searchable online database (www.mdsgene.org), which also provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including early onset (median age at onset of ∼30 years for carriers of at least 2 mutations in any of the 3 genes) of an overall clinically typical form of PD with excellent treatment response, dystonia and dyskinesia being relatively common and cognitive decline relatively uncommon. However, when comparing actual data with common expert knowledge in previously published reviews, we detected several discrepancies. We conclude that systematic reporting of phenotypes is a pressing need in light of increasingly available molecular genetic testing and the emergence of first gene-specific therapies entering clinical trials. © 2018 International Parkinson and Movement Disorder Society.

Correlating quantitative tractography at 3T MRI and cognitive tests in healthy older adults.

This study used diffusion tensor imaging tractography at 3 T MRI to relate cognitive function to white matter tracts in the brain. Brain T2 fluid attenuated inversion recovery-weighted and diffusion tensor 3 T MRI scans were acquired in thirty-three healthy participants without mild cognitive impairment or dementia. They completed a battery of neuropsychological tests including the Montreal Cognitive Assessment, Stroop test, Trail Making Test B, Wechsler Memory Scale-III Longest span forward, Wechsler Memory Scale-III Longest span backward, Mattis Dementia Rating Scale, California Verbal Learning Test Version II Long Delay Free Recall, and Letter Number Sequencing. Tractography was generated by the Fiber Assignment by Continuous Tracking method. The corpus callosum, cingulum, long association fibers, corticospinal/bulbar tracts, thalamic projection fibers, superior cerebellar peduncle, middle cerebellar peduncle and inferior cerebellar peduncle were manually segmented. The fractional anisotropy (FA) and mean diffusivity (MD) of these tracts were quantified. We studied the association between cognitive test scores and the MD and FA of tracts while controlling for age and total white matter hyperintensities volume. Worse scores on the Stroop test was associated with decreased FA of the corpus callosum, corticospinal/bulbar tract, and thalamic projection tracts. Scores on the other cognitive tests were not associated with either the FA or MD of measured tracts. In healthy persons the Stroop test appears to be a better predictor of the microstructural integrity of white matter tracts measured by DTI tractography than other cognitive tests.

Cognitive Function and 3-Tesla Magnetic Resonance Imaging Tractography of White Matter Hyperintensities in Elderly Persons.

BACKGROUND/AIMS: This study used 3-Tesla magnetic resonance imaging (MRI) tractography to determine if there was an association between tracts crossing white matter hyperintensities (WMH) and cognitive function in elderly persons. METHODS: Brain T2-weighted fluid-attenuated inversion recovery (FLAIR) and diffusion tensor MRI scans were acquired in participants above the age of 60 years. Twenty-six persons had WMH identified on T2 FLAIR scans. They completed a battery of neuropsychological tests and were classified as normal controls (n = 15) or with Alzheimer's dementia (n = 11). Tractography was generated by the Fiber Assignment by Continuous Tracking method. All tracts that crossed WMH were segmented. The average fractional anisotropy and average mean diffusivity of these tracts were quantified. We studied the association between cognitive test scores with the average mean diffusivity and average fractional anisotropy of tracts while controlling for age, total WMH volume and diagnosis. RESULTS: An increased mean diffusivity of tracts crossing WMH was associated with worse performance on the Wechsler Memory Scale-III Longest Span Forward (p = 0.02). There was no association between the fractional anisotropy of tracts and performance on cognitive testing. CONCLUSION: The mean diffusivity of tracts crossing WMH measured by tractography is a novel correlate of performance on the Wechsler Memory Scale-III Longest Span Forward in elderly persons.