Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

Abstract

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N = 17), patients with mild cognitive impairment (MCI, N = 13), and cognitively normal controls (N = 18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR = 0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms.

APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

“…We found an increase in amyloid deposition and abnormal levels of CSF amyloid and tau in older adults with SMC, which was strongly associated with APOE ε4 carrier status. However, we did not observe differences in glucose metabolism and MTL atrophy in this population, even in SMC APOE ε4+, as has been previously reported [4, 13, 17, 19, 21, 23, 28, 46, 47]. Given the previous research in participants with SCD/SMC, the lack of hypometabolism or atrophy is somewhat surprising.…”

“…In the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a comparable group of older adults were recruited with significant memory concerns (SMC) in form of self-only complaints exceeding a predefined cut-off score on memory ratings. Previous studies have shown that older adults with SCD/SMC have an increased risk for future progression to AD [5–16], as well as AD-like changes in neuroimaging and cerebrospinal fluid (CSF) biomarkers [4, 13, 17–27]. In addition, SCD/SMC participants who are carriers of the most commonly reported genetic variant associated with late onset AD, the apolipoprotein E ( APOE) ε4 allele, show greater medial temporal lobe (MTL) hypometabolism and atrophy, increased cerebral amyloid, as well as altered CSF measures of amyloid and tau [22, 23, 28, 29].…”

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging

“…It has been suggested that decreased NAA concentrations reflect reduced neuronal density or neuronal function 19, 21 . Both reasons could be responsible for our observations of age-related [NAA] reductions.…”

Utility of the Cognitive Difficulties Scale and Association With Objective Test Performance

“…Age-related changes occur in the brain, and Alzheimer's disease (AD)-related pathology can be seen even prior to diagnosis of MCI. [1][2][3][4] Early identification of individuals at risk of cognitive decline is important in order to implement appropriate treatments early in the disease process.…”