White Matter Hyperintensities and Cognitive Impairment in Healthy and Pathological Aging: A Quantified Brain MRI Study.

BACKGROUND: Brain changes involving the white matter (WM), often an indication of cerebrovascular pathology, are frequently seen in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Few studies have examined possible cognitive domain- or group-specific cognitive effects of WM pathology in old age, MCI, and AD. OBJECTIVE: Our purpose was to examine the relationship between WM hyperintensities (WMH), a typical marker for WM pathology, and cognitive functioning in healthy old age and pathological aging using quantified MRI data. METHODS: We utilized multidomain neuropsychological data and quantified MRI data from a sample of 42 cognitively healthy older adults and 44 patients with MCI/AD (total n = 86). RESULTS: After controlling for age and education, WMH in the temporal and parieto-occipital lobes was associated with impairments in processing speed and parieto-occipital pathology with verbal memory impairment in the whole sample. Additionally, temporal WMH was associated with impaired processing speed in the patient group specifically. CONCLUSIONS: WM pathology is strongly associated with impaired processing speed, and our results indicate that these impairments arise from WMH in the temporal and parieto-occipital regions. In MCI and AD patients with temporal WMH, processing speed impairments are especially prominent. The results of this study increase our knowledge of cognitive repercussions stemming from temporal and/or parieto-occipital WM pathology in healthy and pathological aging.

Effects of White Matter Hyperintensities on Verbal Fluency in Healthy Older Adults and MCI/AD.

BACKGROUND: White matter hyperintensities (WMHs) are markers for cerebrovascular pathology, which are frequently seen in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Verbal fluency is often impaired especially in AD, but little research has been conducted concerning the specific effects of WMH on verbal fluency in MCI and AD. OBJECTIVE: Our aim was to examine the relationship between WMH and verbal fluency in healthy old age and pathological aging (MCI/AD) using quantified MRI data. METHODS: Measures for semantic and phonemic fluency as well as quantified MRI imaging data from a sample of 42 cognitively healthy older adults and 44 patients with MCI/AD (total n = 86) were utilized. Analyses were performed both using the total sample that contained seven left-handed/ambidextrous participants, as well with a sample containing only right-handed participants (n = 79) in order to guard against possible confounding effects regarding language lateralization. RESULTS: After controlling for age and education and adjusting for multiple correction, WMH in the bilateral frontal and parieto-occipital areas as well as the right temporal area were associated with semantic fluency in cognitively healthy and MCI/AD patients but only in the models containing solely right-handed participants. CONCLUSION: The results indicate that white matter pathology in both frontal and parieto-occipital cerebral areas may have associations with impaired semantic fluency in right-handed older adults. However, elevated levels of WMH do not seem to be associated with cumulative effects on verbal fluency impairment in patients with MCI or AD. Further studies on the subject are needed.

Domain-specific cognitive effects of white matter pathology in old age, mild cognitive impairment and Alzheimer's disease.

Concomitant white matter (WM) brain pathology is often present in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Cognitive effects of WM pathology on cognition in normal and pathological aging have been studied, but very little is known about possible group-specific effects in old age, MCI and AD. The purpose of the current study was to examine the relationship between WM pathology and cognitive functioning in four cognitive domains in old age, MCI and AD. The study utilized multi-domain neuropsychological data and visually rated MRI imaging data from a sample of 56 healthy older adults, 40 patients with MCI and 52 patients with AD (n = 148). After controlling for age and education, main effects of frontal WM pathology (especially in the left hemisphere) were found for cognitive performances in two domains, whereas a main effect of parieto-occipital WM pathology was only found for processing speed. In addition, with regard to processing speed, an interaction between group and WM changes was found: Patients with AD that had moderate or severe left frontal WM pathology were considerably slower than patients with AD that had milder cerebrovascular pathology. Frontal WM pathology, especially in the left hemisphere, seems to affect cognitive functions in many domains in all three groups. The results of the study increase our knowledge of cognitive repercussions stemming from frontal and/or parieto-occipital WM pathology in AD. Clinicians should be aware that patients with AD with prominent frontal cerebrovascular pathology can have considerably slowed cognitive processing.

Cognitive Effects of White Matter Pathology in Normal and Pathological Aging.

We examined whether cerebrovascular white matter pathology is related to cognition as measured by the compound score of CERAD neuropsychological battery in cognitively normal older adults, patients with mild cognitive impairment, and patients with Alzheimer's disease (total n = 149), controlling for age and education. Trend-level effects of white matter pathology on cognition were only observed in patients with Alzheimer's disease (p = 0.062, η2  = 0.052), patients with severe frontal white matter pathology performed notably worse than those with milder pathology. This indicates that frontal cerebrovascular pathology may have an additive negative effect on cognition in Alzheimer's disease.