Three sets of research criteria are available for diagnosis of Alzheimer’s disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer’s disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer’s disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer’s disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer’s disease at the mild cognitive impairment stage and progression to Alzheimer’s disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer’s disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer’s disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer’s disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer’s disease likelihood group. The 3-year progression rate to Alzheimer’s disease-type dementia was 59% in the high Alzheimer’s disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer’s disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer’s disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer’s disease likelihood group or the International Working Group-2 prodromal Alzheimer’s disease group could be considered.

Humans can recollect past events in details (recollection) and/or know that an object, person, or place has been encountered before (familiarity). During the last two decades, there has been intense debate about how recollection and familiarity are organized in the brain. Here, we propose an integrative memory model which describes the distributed and interactive neurocognitive architecture of representations and operations underlying recollection and familiarity. In this architecture, the subjective experience of recollection and familiarity arises from the interaction between core systems (storing particular kinds of representations shaped by specific computational mechanisms) and an attribution system. By integrating principles from current theoretical views about memory functioning, we provide a testable framework to refine the prediction of deficient versus preserved mechanisms in memory-impaired populations. The case of Alzheimer's disease (AD) is considered as an example because it entails progressive lesions starting with limited damage to core systems before invading step-by-step most parts of the model-related network. We suggest a chronological scheme of cognitive impairments along the course of AD, where the inaugurating deficit would relate early neurodegeneration of the perirhinal/anterolateral entorhinal cortex to impaired familiarity for items that need to be discriminated as viewpoint-invariant conjunctive entities. The integrative memory model can guide future neuropsychological and neuroimaging studies aiming to understand how such a network allows humans to remember past events, to project into the future, and possibly also to share experiences.

Memory consolidation benefits from sleep. In addition to strengthening some memory traces, another crucial, albeit overlooked, function of memory is to erase irrelevant information. Directed forgetting is an experimental approach consisting in presenting “to be remembered” and “to be forgotten” information that allows selectively decreasing or increasing the strength of individual memory traces according to the instruction provided at learning. This paradigm was used in combination with functional MRI to determine, in humans, what specifically triggers at encoding sleep-dependent compared with time-dependent consolidation. Our data indicate that relevant items that subjects strived to memorize are consolidated during sleep to a greater extent than items that participants did not intend to learn. This process appears to depend on a differential activation of the hippocampus at encoding, which acts as a signal for the offline reprocessing of relevant memories during postlearning sleep episodes.

In normal aging, memory for associations declines more than memory for individual items. Unitization is an encoding process defined by creation of a new single entity to represent a new arbitrary association. The current study tested the hypothesis that age-related differences in associative memory can be reduced by encoding instructions that promote unitization. In two experiments, groups of 20 young and 20 older participants learned new associations between a word and a background color under two conditions. In the item detail condition, they had to imagine that the item is the same color as the background-an instruction promoting unitization of the associations. In the context detail condition, which did not promote unitization, they had to imagine that the item interacted with another colored object. At test, they had to retrieve the color that was associated with each word (source memory). In both experiments, the results showed an age-related decrement in source memory performance in the context detail but not in the item detail condition. Moreover, Experiment 2 examined receiver operating characteristics in older participants and indicated that familiarity contributed more to source memory performance in the item detail than in the context detail condition. These findings suggest that unitization of new associations can overcome the associative memory deficit observed in aging, at least for item-color associations.