Dementia associated with disorders of the basal ganglia

Abstract

Dementia is now the leading cause of death in the United Kingdom, accounting for over 12% of all deaths and is the fifth most common cause of death worldwide. As treatments for heart disease and cancers improve and the population ages, the number of sufferers will only increase, with the chance of developing dementia doubling every 5 years after the age of 65. Finding an effective treatment is ever more critical to avert this pandemic health (and economic) crisis. To date, most dementia‐related research has focused on the cortex and the hippocampus; however, with dementia becoming more fully recognized as aspects of diseases historically categorized as motor disorders (e.g., Parkinson's and Huntington's diseases), the role of the basal ganglia in dementia is coming to the fore. Conversely, it is highly likely that neuronal pathways in these structures traditionally considered as spared in Alzheimer's disease are also affected, particularly in later stages of the disease. In this review, we examine some of the limited evidence linking the basal ganglia to dementia.

Human Brain Lipidomics: Pilot Analysis of the Basal Ganglia Sphingolipidome in Parkinson’s Disease and Lewy Body Disease

“…The basal ganglia constitute a collection of subcortical nuclei that influence motor and cognitive processes, with degradation of this region being well-established in PD and LBD [25][26][27]. Loss of ~80% of the dopaminergic neurons in the nigrostriatal pathway (projections from the substantia nigra pars compacta to the striatum [i.e., putamen + caudate nucleus]) precipitates extrapyramidal motor symptoms [28].…”

Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease

“…Among the associated variants, it is interesting to mention the rs3745198 ( PLD3 ), rs62182086 ( PNKD ), rs3734050 ( FAT2 , FAT Atypical Cadherin 2 ), which are reported as significant expression Quantitative Loci (eQTLs) in basal ganglia and cortex on Gtex portal 1 . Both regions of the brain are known to be affected by neurodegenerative processes ( Ferese et al, 2015 ; Yacoubian, 2017 ; Vitanova et al, 2019 ) and the above-mentioned genes have been associated with neurological disorders mediated by degenerative mechanisms, including LOAD ( PLD3 ), spinocerebellar ataxia ( FAT2 , PLD3 ), paroxysmal non-kinesigenic dyskinesia ( PNKD ) ( Nibbeling et al, 2017 ; Tan et al, 2019 ; Garone et al, 2020 ). Indeed, these variants could be further explored as potential biomarkers associated with a higher predisposition to develop neurodegenerative disorders, in combination with other contributing factors.…”

Aripiprazole-Associated Acute Dystonia During Dose Reduction in Patient With Schizophrenia and Dementia

“…Furthermore, patients with dementia might be more vulnerable to the effect because of the age-related reduction of dopaminergic neurons in the basal ganglia and substantia nigra, which may bring down the threshold of dystonic reactions. 12,13 In addition, cases of withdrawal-emergent dyskinesia, a subtype of tardive dyskinesia, were also reported after sudden discontinuation of antipsychotics and the phenomenon should be kept in mind in aging populations. 14 In conclusion, a 61-year-old woman with schizophrenia and dementia developed an oculogyric crisis during dose reduction of aripiprazole from 20 to 10 mg/d.…”

“…Upon abrupt reduction of aripiprazole, the imbalance of dopaminergic and cholinergic neurotransmitters exacerbates. Furthermore, patients with dementia might be more vulnerable to the effect because of the age-related reduction of dopaminergic neurons in the basal ganglia and substantia nigra, which may bring down the threshold of dystonic reactions 12,13 . In addition, cases of withdrawal-emergent dyskinesia, a subtype of tardive dyskinesia, were also reported after sudden discontinuation of antipsychotics and the phenomenon should be kept in mind in aging populations 14 …”