The Course of Cognitive Impairment in Preclinical Alzheimer Disease

Small, Brent J.; Fratiglioni, Laura; Viitanen, Matti; Winblad, Bengt; Bäckman, Lars

doi:10.1001/archneur.57.6.839

Cited by 306 publications

(231 citation statements)

References 27 publications

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“…Numerous studies have now shown that subtle cognitive changes can precede the diagnosis of AD by a few years or more (Bäckman et al, 2001;Bondi et al, 1994Bondi et al, , 1995Bondi et al, , 1999Chen et al, 2001;Lange et al, 2002;Linn et al, 1995;Masur et al, 1994;Rubin et al, 1998;Small et al, 1998Small et al, , 2000Smith et al, 1998). As Sliwinski and colleagues (1996) have shown, the inclusion of such individuals with preclinical AD in a normative sample leads to an underestimate of the mean, an overestimate of the variance, and an overestimate of the effect of age on a given cognitive measure, all of which reduces the sensitivity of the measure for detecting mild impairment.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

Bondi

Houston

Salmon

et al. 2003

J Int Neuropsychol Soc

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The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age < 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; VeryOld: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions. Young-Old AD and Very-Old AD groups were comparable in education, gender, dementia severity, and disease duration. Results showed that both AD groups achieved comparable raw scores on all the neuropsychological measures. However, when scores were standardized on the basis of performance of their respective NC groups (i.e., age-corrected z scores), Very-Old AD patients significantly outperformed Young-Old AD patients on tests of executive functions, visuospatial skills, and delayed memory. Furthermore, the relationship between age and memory and executive function deficits in AD was modified by APOE genotype. These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old.

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Section: Discussionmentioning

confidence: 99%

Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

Bondi

Houston

Salmon

et al. 2003

J Int Neuropsychol Soc

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“…The association, while not necessarily causal, is of concern. Verbal episodic memory is sensitive to cognitive aging (Weintraub et al, 2009), and impaired performance in this domain is linked to development of Alzheimer's disease later in life (Chen et al, 2000;Small et al, 2000). Observed associations for endogenous testosterone levels do not necessarily predict effects of exogenous testosterone therapy administered at pharmacological doses, but findings suggest the need for further study when off-label testosterone therapy is considered for midlife women.…”

Section: Concluding Perspectivesmentioning

confidence: 99%

“…We were particularly interested in associations with verbal episodic memory, a cognitive domain where poor performance is especially linked to increased dementia risk (Chen et al, 2000;Small et al, 2000). Total and free estradiol and testosterone levels, the ratio of these two hormones, and estrone were tested for association with cognition and with cognitive change over a two-year period.…”

Section: Introductionmentioning

confidence: 99%

Hormone levels and cognitive function in postmenopausal midlife women

Ryan

Stanczyk

Dennerstein

et al. 2012

Neurobiology of Aging

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Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the populationbased Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions two years apart. Participants (n=148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p=0.02) and free (p=0.03) estradiol levels and a lower ratio of testosterone to estradiol (p=0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p=0.08) and lower testosterone/estradiol ratio (p=0.06). Lower free testosterone levels were associated with greater two-year improvement on verbal episodic memory (p=0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p=0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.

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“…Deficits in episodic memory can be evidenced using neuropsychological tests that require remembering word lists, figures and faces over a period of time ranging from several minutes to one week. Impairment in delayed recall seems to be one of the best predictors of future dementia (Small et al, 2000;Ivanoiu et al, 2005). Semantic memory, which concerns general world knowledge, is also impaired in AD, even at the pre-dementia stages of the disease (Chertkow and Bub, 1990;Duong et al, 2006;Joubert et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment

Joubert

Gour

Guedj

et al. 2016

Cortex

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The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study.All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition.Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that a genuine semantic impairment may represent one of the clinical hallmarks of LOAD.

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The Course of Cognitive Impairment in Preclinical Alzheimer Disease

Abstract: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered. Arch Neurol. 2000.

Cited by 306 publications

References 27 publications

Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

Hormone levels and cognitive function in postmenopausal midlife women

Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment

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