Widespread Decreases in Cerebral Copper Are Common to Parkinson's Disease Dementia and Alzheimer's Disease Dementia

 With your likely chances of getting dementia or Parkinsons post stroke, you'll want your doctor to have protocols to address and prevent this problem from occurring. You do expect your doctor to do the proper doctor thing and know exactly how to prevent these complications? That is what doctors are for, isn't it? My dad had PDD but there was no treatment at all. Luckily Parkinsons is not hereditary.

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

5. Parkinson’s Disease May Have Link to Stroke March 2017

The latest here:

Widespread Decreases in Cerebral Copper Are Common to Parkinson's Disease Dementia and Alzheimer's Disease Dementia

 

Melissa Scholefield^1*, Stephanie J. Church¹, Jingshu Xu¹, Stefano Patassini², Federico Roncaroli^3,4, Nigel M. Hooper⁵, Richard D. Unwin^1,6 and Garth J. S. Cooper^1,2

• ¹Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, Centre for Advanced Discovery & Experimental Therapeutics, School of Medical Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
• ²Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
• ³Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Manchester, United Kingdom
• ⁴Division of Neuroscience and Experimental Psychology, Faculty of Brain and Mental Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
• ⁵Division of Neuroscience & Experimental Psychology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom
• ⁶Stoller Biomarker Discovery Centre & Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, United Kingdom

Several studies of Parkinson's disease (PD) have reported dysregulation of cerebral metals, particularly decreases in copper and increases in iron in substantia nigra (SN). However, few studies have investigated regions outside the SN, fewer have measured levels of multiple metals across different regions within the same brains, and there are no currently-available reports of metal levels in Parkinson's disease dementia (PDD). This study aimed to compare concentrations of nine essential metals across nine different brain regions in cases of PDD and controls. Investigated were: primary motor cortex (MCX); cingulate gyrus (CG); primary visual cortex (PVC); hippocampus (HP); cerebellar cortex (CB); SN; locus coeruleus (LC); medulla oblongata (MED); and middle temporal gyrus (MTG), thus covering regions with severe, moderate, or low levels of neuronal loss in PDD. Levels of eight essential metals and selenium were determined using an analytical methodology involving the use of inductively-coupled plasma mass spectrometry (ICP-MS), and compared between cases and controls, to better understand the extent and severity of metal perturbations. Findings were also compared with those from our previous study of sporadic Alzheimer's disease dementia (ADD), which employed equivalent methods, to identify differences and similarities between these conditions. Widespread copper decreases occurred in PDD in seven of nine regions (exceptions being LC and CB). Four PDD-affected regions showed similar decreases in ADD: CG, HP, MTG, and MCX. Decreases in potassium and manganese were present in HP, MTG and MCX; decreased manganese was also found in SN and MED. Decreased selenium and magnesium were present in MCX, and decreased zinc in HP. There was no evidence for increased iron in SN or any other region. These results identify alterations in levels of several metals across multiple regions of PDD brain, the commonest being widespread decreases in copper that closely resemble those in ADD, pointing to similar disease mechanisms in both dementias.

Introduction

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, affecting around 1% of the world's population above the age of 60 (Tysnes and Storstein, 2017). Clinically, PD is characterized by progressive motor dysfunction resulting in bradykinesia, tremor, and rigidity. Cognitive impairment is also common, with cohort studies reporting around a third of patients as showing mild cognitive impairment (MCI) at the time of diagnosis, and up to 80% developing dementia within 20 years after onset of symptoms (Hanagasi et al., 2017). When dementia has developed, the condition is described as PD with dementia (also known as Parkinson's disease dementia, and Parkinsonian dementia) and abbreviated as PDD.

PD and PDD are characterized by the degeneration of dopaminergic neurons in the substantia nigra and the accumulation of misfolded α-synuclein in Lewy bodies and neuropil threads (Braak et al., 2003). However, research is ongoing on exactly how these inclusions develop or how they lead to neuronal death. Although clinical trials targeting the aggregation and binding of α-synuclein, and/or aiming to changes its levels are ongoing, to date no drugs modifying misfolded α-synuclein have been developed (Oliveri, 2019).

Therefore, research in PD is beginning to focus on other mechanisms that may contribute to pathogenesis, including the roles of mitochondrial dysfunction and oxidative stress (Rocha et al., 2018), autophagy (Cerri and Blandini, 2019), genetic factors (Raza et al., 2019), lipid dysfunction (Xicoy et al., 2019), inflammation (Rocha et al., 2018), and metal homeostasis (Ward et al., 2014; Bjorklund et al., 2018). Perturbations of metals have been reported in PD brain tissues. Increases in iron (Fe) have been consistently reported in the substantia nigra (SN), the region most severely affected in PD (Dexter et al., 1989; Ayton et al., 2013; Kim and Lee, 2014; Pyatigorskaya et al., 2015; Costa-Mallen et al., 2017; Genoud et al., 2017; Xuan et al., 2017). Likewise, there have been several reports of reduced copper (Cu) within the SN (Ayton et al., 2013; Davies et al., 2014; Genoud et al., 2017). Some studies examined other brain regions, usually observing no changes in Cu outside the SN (Riederer et al., 1989; Ayton et al., 2013; Genoud et al., 2017), but with one study showing decreases in the caudate nucleus (CN) and locus coeruleus (LC) (Davies et al., 2014). Additionally, most investigations did not distinguish between PD and PDD and primarily focused on the former; indeed, there are no available studies known to us reporting brain metal levels in PDD itself. It therefore remained unknown whether different or additional metal alterations characterize PDD.

To answer this question, we investigated levels of eight essential metals including sodium (Na), magnesium (Mg), potassium (K), calcium (Ca), manganese (Mn), Fe, Cu, zinc (Zn), and selenium (Se), across nine brain regions including the cerebellum at the level of the dentate nucleus (CB), cingulate gyrus (CG), hippocampus (HP), LC, motor cortex (MCX), medulla (MED), middle temporal gyrus (MTG), occipital cortex at the level of the primary visual cortex (PVC), and SN in nine confirmed cases of PDD and nine age-matched control brains. Essential metals were chosen for investigation due to the physiological necessity of tightly-controlled levels for health and survival in humans, as well as on the basis of previous reports of alterations of such elements not only in PD, but also across multiple brain regions in other neurodegenerative conditions such as Alzheimer's (AD) (Deibel et al., 1996; Loeffler et al., 1996; Xu et al., 2017) and Huntington's disease (HD) (Bartzokis et al., 2007; Reetz et al., 2012; Rosas et al., 2012). The regions selected here were chosen to cover areas highly affected by neurodegeneration in PD/PDD (SN, MED, LC), as well as moderately-affected regions (MCX, HP, PVC, CG) and relatively-spared regions (CB, MTG). In addition to allowing direct comparison of areas differently affected by neurodegeneration, this selection was also expected to allow comparison of results with those of previous parallel studies investigating metallomic perturbations in ADD, in order to identify any similarities or differences between the two forms of dementia. Any identified similarities could point toward shared disturbances or pathogenic mechanisms between these diseases, whilst differences could aid in distinguishing between conditions in cases where clinical presentation may make diagnosis and treatment difficult.

More at link.