Aging is associated with an increased risk for developing vascular pathology in cerebral white matter (WM). These brain changes can have a variety of cognitive repercussions, ranging from insignificant to mild cognitive impairment to dementia. Concomitant WM pathology is also frequently found in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Previous research generally supports the notion that WM pathology and AD-related pathology would have a cumulative impairing effect on cognition, but relatively few studies have focused on studying these effects. Thus, the aim of this thesis was to investigate the effects of WM pathology on cognitive function in cognitively healthy older adults and patients with MCI or AD. Study I investigated the effects of WM pathology on general cognitive functioning as measured by the CERAD-NB and utilized visual ratings of magnetic resonance imaging (MRI) data. Here, AD patients with severe frontal WM pathology had markedly lower performances than AD patients with milder pathology. Study II utilized the same sample as Study I but expanded the scope of analysis to include four specific cognitive domains. Frontal WM pathology was associated with lower cognitive performance in processing speed and visual memory, and parieto-occipital WM pathology solely with processing speed, in all groups. Furthermore, notably slower processing speed performance was seen in AD patients with moderate or severe left frontal WM pathology than in AD patients with less cerebrovascular pathology in that region. Study III included the same four cognitive domains as Study II but utilized quantitative volumetric measurements of WM pathology. A portion of the sample used in Study II had to be excluded due to inadequate MRI resolution, which resulted in combining the MCI and AD groups into a single patient group. Overall, temporal and parieto-occital WM pathology were associated with lower processing speed, and parieto-occipital WM pathology with lower verbal memory. Furthermore, a group-specific effect was seen in the follow-up analyses: Here WM pathology in the left temporal lobe was associated with lower processing speed only in MCI or AD patients. Study IV utilized the same sample and image analysis methods as Study III but focused solely on verbal fluency. Here, WM pathology in bilateral frontal, bilateral parieto-occipital and right temporal areas was associated with semantic fluency in right-handed participants. However, no cumulative effects on verbal fluency impairment were seen specifically in patients with MCI or AD. The results of this thesis support the notion that WM pathology and AD-related pathologies can have cumulative effects on cognition. More specifically, AD patients who have major levels of WM pathology especially in frontal cerebral areas are likely to exhibit more cognitive impairments when compared to patients with milder levels of WM pathology. Impairments may show up as slowed information processing speed and lowered general cognitive functioning, which can be detected with general-level cognitive measures such as the Total Score of the CERAD-NB. As previous studies have shown that the prevalence of WM pathology can be lowered by minimizing modifiable risk factors and fostering physical and cognitive activity, the pre-emptive targeting of these factors is likely to yield long-term benefits in maintaining cognition in MCI and AD.
|Qualification||Doctor of Philosophy|
|Award date||12 Oct 2021|
|Place of Publication||Åbo|
|Publication status||Published - 7 Sep 2021|
|MoE publication type||G5 Doctoral dissertation (article)|