Changes to the lateral geniculate nucleus in Alzheimer's disease but not dementia with Lewy bodies

Abstract

Aims: Complex visual hallucinations occur in 70% of dementia with Lewy bodies (DLB) cases and significantly affect patient well-being. Visuo-cortical and retinal abnormalities have been recorded in DLB and may play a role in visual hallucinations. The present study aimed to investigate the lateral geniculate nucleus (LGN), a visual relay centre between the retina and visual cortex, to see if changes to this structure underlie visual hallucinations in DLB.

Methods: Fifty-one [17 probable DLB, 19 control and 15 probable Alzheimer's disease (AD)] cases were recruited for a functional magnetic resonance imaging study, in which patients' response to a flashing checkerboard stimulus was detected and measured in the LGN, before comparison across experimental groups. Additionally, post mortem LGN tissue was acquired for a cross-sectional study using 20 (six DLB, seven control and seven AD) cases and analysed using stereology. α-Synuclein, phosphorylated tau and amyloid-β pathology was also assessed in all cases.

Results: DLB cases did not significantly differ from controls on neuroimaging, morphometry or pathology. However, a significant increase in amyloid-β pathology, a reduction in number of parvocellular neurones and magnocellular gliosis was found in AD cases compared with control and DLB cases.

Conclusions: These findings suggest that the early visual system is relatively spared in DLB, which implies that upstream visual structures may be largely responsible for the generation of hallucinatory percepts. The significance of the degeneration of the LGN in AD cases is uncertain.

Keywords: dementia with Lewy bodies; fMRI; lateral geniculate nucleus; neuropathology; stereology.

Figure 1

The structure of the LGN. (a) Shows a typical LGN approximately in the middle coronal level, with clear lamination. (b) Shows how the LGN was divided into magnocellular (black) and parvocellular (grey). (c) Shows typical LGN cells with a point grid, and (d) shows disector frames used to perform neuronal and glial cell counts within the LGN. Scale bars: (a) and (b) = 1 mm, (c) = 200 μm and (d) = 10 μm.

Figure 2

fMRI image of activation in response to checkerboard stimulus in the whole group, overlaid on an age‐matched average structural scan. Crosshair is centred on the right LGN. Yellow‐red colour scale shows the t statistic, thresholded at P < 0.001 (uncorrected for multiple comparisons).

Figure 3

Bar chart showing percentage area stained by antibodies in the LGN across groups (*P = 0.005).