Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson's disease

Abstract

We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (−1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: −0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and Aβ42/Aβ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD.

In vivo coupling of tau pathology and cortical thinning in Alzheimer's disease

“…However, evidence from postmortem and positron emission tomography (PET) studies has not been able to demonstrate strong associations of amyloid β (Aβ) with neuronal loss or disease severity in AD [2,3]. In contrast, NFTs accumulate in tandem with neuronal loss, disease progression, and show strong correlations with clinical phenotypes [4–6], findings which have since been corroborated by cerebrospinal fluid evidence implicating tau as a key substrate of brain atrophy across various neurodegenerative conditions [7–10].…”

Schizophrenia-related microdeletion causes defective ciliary motility and brain ventricle enlargement via microRNA-dependent mechanisms in mice

“…Hydrocephalic animals develop severe lesions and die at 20-40 days of age 73 , but there is no abnormal mortality in 22q11DS mice at this age. In humans and mice, ventricular volumes progressively increase during normal aging; 6,7,74 this enlargement also has been often observed in neurological disorders, such as Alzheimer disease, vascular dementia, bipolar disorder, copy number variation disorders, and Parkinson disease [1][2][3][4][5]75 . However, evidence of ventricular enlargement in SCZ is overwhelming and reported in more than 80% of SCZ studies 13 .…”

“…T he volume of cerebral ventricles often increases in various neurologic and psychiatric disorders, such as Parkinson disease 1 , Alzheimer disease 2 , vascular dementia 3 , bipolar disorder 4 , copy number variation disorders 5 , as well as during normal aging [6][7][8] . In individuals with schizophrenia (SCZ), cerebral ventricular enlargement is one of the most common and replicable findings; it has been observed in more than 80% of SCZ studies [9][10][11][12][13][14][15][16] .…”

Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood

“…Progressive enlargement of the ventricular system is a common finding in several neurologic and psychiatric disorders including dementia ( 36 ), Parkinson’s disease ( 37 ), multiple sclerosis ( 38 , 39 ), schizophrenia ( 40 ) and it has been extensively discussed in the context of brain cerebral atrophy and cognitive impairment ( 41 ). Interestingly, ventricular enlargement has been suggested as a neuroimaging-based biomarker in normal aging ( 42 , 43 ), which may herald the cognitive decline associated with the onset and progression of Alzheimer’s disease ( 44 – 46 ).…”