Braak stage and cognitive status of patients with Parkinson’s disease

Cognitive function appears to decrease steadily as PD progresses through the six Braak stages.¹ A Dutch study collected cognitive function data from patients with PD.¹ The investigators carried out autopsies on the brains of study participants to evaluate the extent of neurodegeneration and Lewy pathology.¹ They found that greater levels of neuropathology – defined in terms of Braak stages – were significantly correlated with Mini-Mental State Examination (MMSE – a test of cognitive functioning) test scores from 12–18 months prior to the patient’s death.1 The average MMSE score consistently decreased from Braak stages 3 to 6, indicating that the risk of developing dementia in PD increases as the disease progresses.¹ The study also suggested that neurodegeneration in the neocortex is not strictly necessary to develop symptoms of dementia; some individuals will experience cognitive decline before the disease spreads to the cortical regions of the brain.¹

Although a seminal publication, and one which provides a powerful framework to conceptualize the neuropathological and clinical progression of PD, there is still much about the neuropathology of PD that is poorly understood, and many refinements and caveats have been added to the Braak model since its conception.^2-7

References:
1.Braak H, Rüb U, Jansen Steur ENH, et al. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 2005; 64 (8): 1404–1410.

2.Borghammer P, Just MK, Horsager J, et al. A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease. NPJ Parkinsons Dis 2022; 8 (1): 166.

3.Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 2003; 110 (5): 517–536.

4.Halliday G, Hely M, Reid W, Morris J. The progression of pathology in longitudinally followed patients with Parkinson’s disease. Acta Neuropathol 2008; 115 (4): 409–415.

5.Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 2007; 33 (6): 599–614.

6.Horsager J, Andersen KB, Knudsen K, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain 2020; 143 (10): 3077–3088.

7.Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 2017; 18 (2): 101–113.