In cross-sectional studies, the cognitive function of carriers of a parkin (PARK2) mutation did not differ from that of non-carriers [46, 47]. However, parkin mutation carriers (heterozygous, compound heterozygous, homozygous) with a disease duration of more than 14 years demonstrated better cognitive performance in attention and executive function domains than non-carriers with similar disease durations [48], suggesting that, similar to motor impairment, cognitive impairment in this more purely dopaminergic (nigropathy) form of parkinsonism may be more slowly progressive.


Carriers of glucocerebrosidase (GBA) mutation demonstrate significantly worse cognitive function than non-carriers, particularly within the domains of memory and processing speed [49]. Likewise GBA mutation represents a risk factor for cognitive impairment and dementia [37], with impaired performance identified on tests of memory (verbal and non-verbal) and visuospatial function in GBA mutation carriers compared with non-carriers with PD [50]. PD patients who were GBA mutation carriers were more likely to be classified as having a Clinical Dementia Rating Scale score of 0.5 or 1 compared with non-carriers [50]. In autopsy studies [51, 52], GBA mutations were associated with cognitive impairment in PD cases that did not meet criteria for AD, suggesting an independent effect of GBA on cognition. This finding has been demonstrated in both patients with PD-D and dementia with Lewy bodies (DLB) [53, 54].


While cross-sectional studies have yielded disparate results, two prospective cohort studies found no association between the APOE e4 genotype and the development of dementia [55] or the rate of change on the Mini-Mental State Examination (MMSE) [56]. One study looked at the rate of change on the Mattis Dementia Rating Scale (MDRS) over time and showed that the e4 allele was associated with a more rapid decline in MDRS scores (three points per year; hazard ratio 2.8) [57]. In the same study, the MAPT H1/H1 haplotype was associated with lower memory scores but was not associated with decline and COMT Met/Met was associated with higher attention scores and did not show decline over time [57].

< Prev   CONTENTS   Source   Next >