Abstract
Magnetic resonance spectroscopy has demonstrated metabolite changes in neurodegenerative disorders such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB); however, their pattern and relationship to clinical symptoms is unclear. To determine whether the spatial patterns of brain-metabolite changes in AD and DLB are regional or diffused, and to examine whether the key metabolite levels are associated with cognitive and non-cognitive symptoms, we acquired whole-brain spatially resolved 3T magnetic resonance spectroscopic imaging (MRSI) data from subjects with AD (N=36), DLB (N=35) and similarly aged controls (N=35). Voxel-wise measurement of N-acetylaspartate to creatine (NAA/Cr), choline to Cr (Cho/Cr), myo-inositol to Cr (mI/Cr) as well as glutamate and glutamine to Cr (Glx/Cr) ratios were determined using MRSI. Compared with controls, AD and DLB groups showed a significant decrease in most brain metabolites, with NAA/Cr, Cho/Cr and mI/Cr levels being reduced in posterior cingulate, thalamus, frontotemporal areas and basal ganglia. The Glx/Cr level was more widely decreased in DLB (posterior cingulate, hippocampus, temporal regions and caudate) than in AD (only in posterior cingulate). DLB was also associated with increased levels of Cho/Cr, NAA/Cr and mI/Cr in occipital regions. Changes in metabolism in the brain were correlated with cognitive and non-cognitive symptoms in the DLB but not in the AD group. The different patterns between AD and DLB may have implications for improving diagnosis, better understanding disease-specific neurobiology and targeting therapeutics. In addition, the study raised important questions about the role of occipital neuroinflammation and glial activation as well as the glutamatergic treatment in DLB.
Highlights
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two commonest subtypes of degenerative dementia in older people.[1]
Alzheimer’s disease (AD) and DLB groups showed a significant decrease in most brain metabolites, with N-acetylaspartate to creatine (NAA/Cr), choline to Cr (Cho/Cr) and myo-inositol to Cr (mI/Cr) levels being reduced in posterior cingulate, thalamus, frontotemporal areas and basal ganglia
Subjects with DLB scored significantly higher in Unified Parkinson’s Disease Rating Scale III (UPDRS) and cognitive fluctuation scale than AD; they did not differ in Mini-Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG) scores
Summary
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two commonest subtypes of degenerative dementia in older people.[1] They share common clinical and neuropsychological features. In DLB, there appears to be an interruption of awareness, which is often associated with transient episodes of confusion and communication difficulties. Remission to near-normal cognitive function can occur spontaneously in the absence of clear environmental triggers. In addition to such cognitive fluctuation, visual hallucinations, which are false perceptions in the absence of an external stimulus that are accompanied by a compelling sense of reality, and motor Parkinsonism are the core clinical features of DLB. These attentional deficits have an important role in other symptoms of DLB such as visual hallucinations.[5]
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