Prodromal Alzheimer's disease: successive emergence of the clinical symptoms.

OBJECTIVE: Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimer's disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow-up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14-year period of follow-up before the dementia phase of AD. METHODS: This study relies on a case-control sample selected from the PAQUID cohort. Of the 3,777 initial subjects of the cohort, 350 subjects experienced development of AD during the 14 years of follow-up. The cases were matched to 350 elderly control subjects. The evolution of scores on cognitive, functional, and depression scales was described throughout the 14-year follow-up using a semiparametric extension of the mixed-effects linear model. RESULTS: The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. Then, more global deficits appeared that were concomitant with an increase in memory complaints and depressive symptoms. About 2 years later, as a consequence of cognitive dysfunction, the subjects started to become slightly dependent in their activities of daily living. In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase. INTERPRETATION: This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase.

Encoding processes influence word-stem completion priming in Alzheimer's disease: a meta-analysis.

Despite the numerous studies focused on priming performances in Alzheimer's disease (AD), the question of whether word-stem completion priming persists in AD is still prone to controversy. Methodological variations, such as encoding instructions, have been proposed to explain the discrepancy of word-stem completion priming results in AD. We conducted a meta-analysis on 678 AD patients and 640 controls to assess whether word-stem completion priming in AD differs according to instructions provided at encoding. When the data across the different encoding instructions were combined, the results showed that AD patients manifest significant completion priming, even though the magnitude of priming is reduced. Taking into account the different encoding conditions, the results suggested that whereas completion priming is impaired in AD when encoding conditions consist in reading or rating words, priming is equivalent to that of controls when encoding conditions require semantic judgments or generating words. In this latter condition in particular, self-generating a word at encoding may provide an aid to partially overcome conceptual deficits of the patients and increase the degree of adequacy between cognitive operations employed at encoding phase and those triggering implicit retrieval.

Gender-related differences in visuospatial memory persist in Alzheimer's disease.

Gender differences in visuospatial cognition favoring men are larger in tasks requiring active information manipulation than in tasks requiring passive storage. This study was designed to determine whether male advantage in active manipulation of visuospatial information can still be evidenced in Alzheimer's disease (AD). Twenty male and 20 female AD patients with equivalent age, education, dementia severity (Mini-Mental State Examination and Mattis Dementia Rating Scale), and visual discrimination abilities were recruited. We administered the forward span of Corsi block-tapping task and Vecchi's matrix memory task involving passive temporary retention of stimuli location. Active manipulation of visuospatial information was assessed with the backward span of Corsi block-tapping task and Vecchi's pathway task in which patients were required to mentally generate a pathway within a matrix. The results showed that scores on the tasks involving passive storage of visuospatial information were equivalent between the two groups of patients, whereas men performed significantly better than women in tasks requiring active manipulation of visuospatial information. This result was limited to visuospatial processing since no difference between male and female patients was evidenced in the verbal short-term memory tasks, neither when the task involved passive storage nor when the task required active processing. Therefore, this study suggests that, besides other variables such as education or lifestyle factors, gender might also modulate the cognitive manifestation of AD.

Exploring different routes of recovery from memory in Alzheimer's disease: evidence for preserved long-term priming.

Studies investigating implicit memory in Alzheimer's disease suggest that priming abilities disappear over time. This study investigates long-term priming in Alzheimer's disease. A total of 20 patients with Alzheimer's disease and 20 controls underwent the Free and Cued Selective Reminding test. After a 30-minute delay, participants were submitted to a word identification task comprising the studied words and new words. The patients exhibited a long-term priming effect similar to that presented by the comparison group. Therefore, whereas explicit retrieval is definitely impaired in Alzheimer's disease, implicit processes allowing the retrieval of that same information operate relatively normally, including after a long delay.