Cognitive functioning in the preclinical stages of Alzheimer´s disease and vascular dementia
Sammanfattning: This doctoral thesis concerns cognitive functioning in the preclinical stages of Alzheimer's disease (AD) and vascular dementia (VaD). It is based on five empirical studies using data from the Kungsholmen Project, a longitudinal population-based study of aging and dementia targeting persons 75 years and older, living in the Kungsholmen District in Stockholm, Sweden. Although the cognitive deficits in the preclinical phase of AD are well documented, some issues have been neglected. One omission is that investigations of preclinical episodic memory deficits have focused solely on retrospective memory (remembering something from the past) and ignored prospective memory (remembering to perform an action in the future). Therefore, Study I compared retrospective and prospective memory functioning in preclinical AD. Prospective memory was impaired three years before the AD diagnosis. More interestingly, the prospective memory impairment was independent of impairment of retrospective memory. This suggests that prospective and retrospective memory partly involve different cognitive operations. Study 1 also showed that different processes within a retrospective memory task (i.e., encoding, storage, and retrieval) were impaired prior to diagnosis. Hence, these data indicate that the episodic memory deficit in preclinical AD generalizes across several important dimensions of this form of memory. In contrast to AD, investigations of the preclinical phase in VaD have been sparse. Studies II and III demonstrated three-year preclinical cognitive deficits on a global measure of cognitive functioning (the Mini-Mental Status Examination), and on three measures of episodic memory functioning (random recall, word recognition, and face recognition) in VaD. Persons in the preclinical stage of AD demonstrated deficits in verbal fluency and visuospatial skills in addition to impairment in global and episodic memory functioning. However, even though the impairments seemed more widespread in preclinical AD, there were no statistically reliable differences between the two preclinical dementia groups. Although the cognitive deficits appear very similar in the preclinical phases of AD and VaD, Study IV demonstrated that verbal fluency could differentiate between the dementia disorders three years prior to diagnosis. Category and letter fluency have partly different neural underpinnings, although both draw on frontal lobe functioning. Whereas category fluency is more dependent on medial-temporal lobe regions, letter fluency is more dependent on frontal-lobe functioning. Category fluency was more impaired in preclinical AD as compared to VaD. This is consistent with histopathological and imaging data indicating that medial-temporal lobe regions are affected early in AD. Letter fluency was equally impaired in AD and VaD, which is consistent with findings of early pathology in the frontal circuitry in the prodromal phases of both diseases. Study V investigated whether individual-difference variables could influence the rate of global cognitive decline during the transition from preclinical to clinical AD. The results from this study demonstrate that many variables which are known to affect cognitive functioning in normal aging (e.g., sex, education, depression, vitamin deficiencies, substance use) or are known to increase the risk of AD (e.g., age, apolipoprotein E epsilon4-allele, poor social network) exerted little influence on the rate of cognitive decline. Thus, even at a preclinical stage, the emerging dementia disease appears to make people more cognitively similar. An exception to this rule was that comorbid diseases acquired during the last three years prior to diagnosis exacerbated the rate of cognitive decline. In conclusion, in preclinical AD most, if not all, aspects of episodic memory functioning seem to be affected. Preclinical cognitive deficits, particularly in episodic memory, can be observed also in VaD. Hence, the similarities in cognitive deficits observed in the clinical stages of these diseases, may be extended to a few years prior to diagnosis. However, despite the similarities, measures such as verbal fluency may be useful in differentiating between the diseases in their preclinical stages. And finally, although most individual-difference variables exert little influence on rate of cognitive decline in the preclinical phase of AD, concomitant diseases may aggravate this decline.
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