Unmasking selective path integration deficits inAlzheimer’s disease risk carriers

Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE4-carriers during a virtual navigation task. We report a selective impairment in APOE4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset

Unmasking selective path integration deficits in Alzheimer’s disease risk carriers

Alzheimer's disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset

Parkinson's disease mild cognitive impairment: application and validation of the criteria

Dementia in Parkinson's disease (PD) is a serious health issue and a major concern for many patients. In most cases mild cognitive impairment (MCI) is considered a transitional stage between normal cognitive functioning and dementia which is of potential importance in the early identification of patients at risk for dementia. Recently, the Movement Disorder Society (MDS) proposed diagnostic criteria for MCI in PD (PD-MCI). These criteria comprise two operationalizations: Level I (based on an abbreviated assessment) and Level II (based on comprehensive neuropsychological evaluation permitting MCI subtyping). These criteria need to be validated. This paper describes a project aiming to validate the MDS PD-MCI criteria by pooling and analyzing cross-sectional and longitudinal neuropsychological databases comprising ≥5,500 PD patients and ≥1,700 controls. After applying the MDS PD-MCI Level I and Level II criteria, rates of conversion to PD-dementia and predictive variables for conversion to PD-dementia will be established. This study will also assist in identifying whether revisions of the PD-MCI criteria are required

Level I PD-MCI Using Global Cognitive Tests and the Risk for Parkinson's Disease Dementia

BackgroundThe criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.MethodsThe MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.ResultsPD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P = <0.001). The C-statistics for MMSE (0.72) and MoCA (0.70) were lower than those based on neuropsychological tests (Level I = 0.82; Level II = 0.81). Sensitivity, specificity and diagnostic accuracy balance was best in Level II.ConclusionMMSE and MoCA predict conversion to PDD. However, Level II neuropsychological assessment seems the preferred assessment for PD-MCI