Alzheimers and Parkinsons: More in common than that which divides?

Both have eponymous names and are linked by neurodegeneration with the build up of abnormal protein deposition. However, Parkinsons and Alzheimers are often studied as separate entities due to clinical symptoms and the different types of proteins which build up - amyloid and tau in Alzheimer's and alpha-synuclein in Parkinson's.

With more recognition of cognitive problems in Parkinsons, however, the question of whether these could be partly caused by Alzheimer's-type pathology has intrigued scientists. We know in Lewy Body Disease, there is evidence of amyloid as well as alpha-synuclein pathology. However, many studies and risk scores looking to predict Parkinson's patients who are more prone to dementia have not included these features - for example this risk score looked at clinical features such as age and cognitive score at baseline http://predictpd.blogspot.co.uk/2017/09/predicting-cognition-in-parkinsons.html.

This study, from investigators in Pennsylvania, specifically looked at whether biomarkers associated with Alzheimer's had any bearing on subsequent development of dementia. 100 Parkinson's patients had genetic blood tests and biochemical spinal fluid tests as well as clinical examination. Of 16 biomarkers assessed, 6 were associated with cognitive decline: total daily dose of dopamine, presence of hallucinations, APOE E4 genotype, COMT genotype, lower CSF Aβ levels, and MRI measure of atrophy. APOE genotype (the commonest sporadic Alzheimers risk gene) had the strongest impact.

This is important in the clinic - assessing for hallucinations and monitoring for cognitive decline in these patients. But also highlights the importance of building connections between the Alzheimers and Parkinsons research communities. Most excitingly, it suggests that treatments currently being developed for Alzheimers may have some role in Parkinsons in the future too.

 

-Anna

http://onlinelibrary.wiley.com/doi/10.1002/mds.27204/full

Mov Disord. 2017 Nov 23. doi: 10.1002/mds.27204. [Epub ahead of print]

APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease.

Tropea TF, Xie SX, Rick J, Chahine LM, Dahodwala N, Doshi J, Davatzikos C, Shaw LM, Van Deerlin V, Trojanowski JQ, Weintraub D, Chen-Plotkin AS.

BACKGROUND:

People with PD are at high risk of developing cognitive impairment and dementia. Cross-sectional studies have identified candidate biomarkers associated with cognitive decline. However, longitudinal studies on this topic are rarer, and few have investigated the use of biomarker panels encompassing multiple modalities. The objective of this study was to find baseline predictors of cognitive decline in longitudinally followed, nondemented Parkinson's disease patients.

METHODS:

We performed a prospective cohort study of 100 PD patients with a median disease duration of 6.4 years. All participants were nondemented at baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical, and MRI-based imaging modalities for their association with longitudinal cognitive decline for up to 8 years. We investigated biomarkers individually, as well as in a multivariate linear mixed-effects model encompassing multimodal biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the primary outcome. Annual consensus process-derived cognitive diagnosis was used for Cox proportional hazards modeling of risk for cognitive decline.

RESULTS:

In multivariate analysis, the presence of the APOE E4 allele, thought disorder, and an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality for recognition of early Alzheimer's disease index) best predicted cognitive decline, with APOE E4 genotype exerting the greatest effect. The presence of the APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P < 0.05). The APOE genotype effect was not specific to any Mattis Dementia Rating Scale-2 domain.

CONCLUSIONS:

Our results confirm the importance of Alzheimer's disease biomarkers as risk factors for cognitive decline in established Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.