Cognitive impairment in preclinical Alzheimer's disease: A meta-analysis.

Abstract

To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (Ͻ 75 years) and shorter follow-up intervals (Ͻ 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory. For global cognitive ability, studies that used population-based sampling yielded larger effect sizes; for episodic memory, larger differences were seen in studies that preidentified groups in terms of baseline cognitive impairment. Within episodic memory, delayed testing and recall-based assessment resulted in the largest effect sizes. The authors conclude that deficits in multiple cognitive domains are characteristic of AD several years before clinical diagnosis. The generalized nature of the deficit is consistent with recent observations that multiple brain structures and functions are affected long before the AD diagnosis.

Slowing of EEG correlates with CSF biomarkers and reduced cognitive speed in elderly with normal cognition over 4 years

“…The posterior localisation of the correlation on the EEG agrees with the cerebral area responsible for the cognitive speed measured by AQT [58]. Meta-analysis of cognitive decline in AD has further presented perceptual speed as one of the first cognitive entity affected [2]. Overall, cognitive decline becomes visible later than biomarkers in AD development [15].…”

Clustering and switching processes in semantic verbal fluency in the course of Alzheimer's disease subjects: Results from the PAQUID longitudinal study

“…The hypothesis of an executive impairment in the preclinical phase of AD is consistent with other studies. Reviews and metaanalyses (Bäckman et al, 2004;Bäckman et al, 2005) of both longitudinal population-based samples and studies on subjects with MCI have evidenced that together with episodic memory deficits, changes in executive functioning and perceptual speed were present in the very early phases. In the same vein, the PAQUID cohort (Amieva et al, 2005) has shown that multiple cognitive functions are affected in the premorbid phase of the AD among which executive …”

Progressive impairment on neuropsychological tasks in a longitudinal study of preclinical Alzheimer's disease.

“…In a detailed review of the literature concerned with preclinical AD, Backman et al (2004Backman et al ( , 2005, for example, argued that the cognitive decline in the 2 or 3 years preceding a nonnormal diagnosis is largely nonspecific. However, they reviewed methodologically diverse studies, many of which did not follow the design guidelines that characterized our study.…”

“…At the other extreme, impairment in preclinical AD patients may exhibit a relatively nonspecific pattern involving similar deficits on the entire battery of neuropsychological tests (cf. Backman et al, 2005).…”