Two separate, large cohorts reveal potential modifiers of age-associated variation in visual reaction time performance.

To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (ntotal = 75,666, nwomen = 47,700, nmen = 27,966; ages 18-85 years old, mean (M)Age = 46.54, standard deviation (SD)Age = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (ntotal = 158,249 nwomen = 89,333 nmen = 68,916; ages 40-70 years old, MAge = 55.81, SDAge = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (ntotal = 39,795, nwomen = 29,640, nmen = 10,155; ages 40-70 years old, MAge = 56.59, SDAge = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.

Smoking is associated with impaired verbal learning and memory performance in women more than men.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.

Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.

Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.

Face memory impairments in patients with frontal lobe damage.

OBJECTIVE: To determine whether damage to prefrontal cortex is associated with face memory impairment. BACKGROUND: Neurophysiologic and functional imaging studies suggest that prefrontal cortex is a key component of a distributed neural network that mediates face recognition memory. However, there have been few attempts to examine the impact of frontal lobe damage on face memory performance. METHODS: Patients with focal frontal lobe lesions and normal control subjects were administered two-alternative forced-choice and single-probe "yes/no" tests of recognition memory for novel faces. Retrograde memory was assessed by using famous faces as stimuli. RESULTS: Compared with control subjects, patients with frontal lobe lesions showed evidence of marked anterograde and relatively mild retrograde face memory impairment. In addition, patients with right frontal lesions demonstrated increased susceptibility to false recognition, consistent with the breakdown of strategic memory retrieval, monitoring, and decision functions. CONCLUSIONS: Prefrontal cortex plays an important role in the executive control of face memory encoding and retrieval. Left and right prefrontal regions seem to make different contributions to recognition memory performance.

Source memory in older adults: an encoding or retrieval problem?

Source memory has been found to be more affected by aging than item memory, possibly because of declining frontal function among older adults. In 4 experiments, the authors explored the role of the frontal lobes (FLs) in source memory, the extent to which they may be involved in the encoding and/or retrieval of source or context, and the conditions under which the source memory deficit in older people may be reduced or eliminated. Results indicated that only a subset of older adults show deficits in source memory, namely those with below average frontal function, and these deficits can be eliminated by requiring people at study to consider the relation between an item and its context. These results provide convincing evidence of the importance of frontal function during the encoding of source and suggest that older adults with reduced FL function fail to initiate the processes required to integrate contextual information with focal content during study.

Prospective memory: a neuropsychological study.

To examine the neuropsychology of prospective remembering, older adults were divided preexperimentally into 4 groups on the basis of their scores on 2 composite measures: one assessing frontal lobe function and the other assessing medial temporal lobe function. The groups reflected the factorial combination of high and low functioning for each neuropsychological system, and they were tested on an event-based laboratory prospective memory task. High-functioning frontal participants showed better prospective remembering than low-functioning frontal participants. There was no significant difference in prospective memory performance attributable to medial temporal functioning. The results support the theoretical notion that frontal lobe processes play a key role in prospective remembering. Discussion focuses on the particular components of prospective memory performance that frontal lobes might mediate.

Dissociation between verbal and autonomic measures of memory following frontal lobe damage.

OBJECTIVE: The objective of this study was to contrast overt verbal versus covert autonomic responses to facial stimuli in a patient with false recognition following frontal lobe damage. BACKGROUND: False recognition has been linked to frontal lobe dysfunction. However, previous studies have relied exclusively on overt measures of memory and have not examined whether or not patients with false recognition continue to demonstrate preserved covert discrimination of familiar and unfamiliar items. METHODS: We recorded skin conductance responses (SCRs) in a patient with frontal lobe damage and in normal control subjects while they performed a familiarity decision task using famous and unfamiliar faces as stimuli. RESULTS: Patient J.S. produced significantly more overt false recognition errors and misidentifications in response to unfamiliar faces than control subjects. However, similar to the control subjects, he showed accurate covert autonomic discrimination of truly familiar faces from unfamiliar ones. Furthermore, SCRs to falsely recognized unfamiliar faces were not significantly different from SCRs generated to unfamiliar faces that J.S. correctly rejected. CONCLUSIONS: Our findings provide further neuropsychological evidence that overt and covert forms of face recognition memory are dissociable. In addition, the failure to detect an autonomic correlate for the false recognition errors and misidentifications in J.S. suggests that these memory distortions were not related to the spurious activation of stored memory representations for specific familiar faces. Instead, these incorrect responses may have been driven by the sense of familiarity evoked by novel faces that had a general resemblance to faces encountered previously. We propose that false recognition in J.S. resulted from the breakdown of strategic frontal memory retrieval, monitoring, and decision functions critical for attributing the experience of familiarity to its appropriate source.

Inhibition of associates and activation of synonyms in the rare-word paradigm: Further evidence for a center--surround mechanism.

Two experiments investigated semantic priming effects in a modified version of the Dagenbach, Carr, and Barnhardt (1990) rare-word paradigm. After learning a list of rare words to a criterion of 50% recall, subjects participated in a lexical decision task in which the rare words served as primes. When the targets were associatively related to the primes, lexical decision responses were facilitated following recalled definitions and inhibited following unrecalled definitions. When the targets were synonyms of the rare words, facilitation occurred following both recalled and unrecalled definitions. The results were interpreted as supporting a center-surround model of attentional retrieval that may serve an adaptive role in new learning.

Learning of name-face associations in memory impaired patients: a comparison of different training procedures.

The purpose of this study was to compare a mnemonic strategy based on concept-drive processing and explicit memory (i.e., verbal elaboration and imagery) to one based on data-driven processing and implicit memory (the method of vanishing cues) in a names and faces learning task. A third training condition that used video presentation was also included. Six American and six German patients with memory impairment attributable to brain injuries of different etiologies attempted to learn the associations between names and faces in each of the three conditions. The mnemonic strategy proved to be the most effective. Discussion focuses on the characteristics of the training procedures and on the nature of the to-be-learned materials as critical determinants of the effectiveness of different training techniques.

Transfer of new learning in memory-impaired patients.

Previous research has produced conflicting evidence concerning transfer of new learning by amnesic patients. The present experiment investigated the hypothesis that different numbers of learning trials account for differences in transfer, such that the greater the number of repetitions of material in identical stimulus contexts the poorer the transfer. Six memory-impaired patients and six control subjects attempted to learn the names of business-related documents in response to descriptive definitions. Learning continued until one of the following criteria was reached: 50% correct, 100% correct, 100% correct plus 10 trials. In a transfer task, subjects were then asked to produce the target responses to altered definitional cues. The results of the experiment demonstrated that, contrary to prediction, transfer improved with numbers of learning trials. Results are consistent with the view that continued study of information allows better integration of new learning with prior knowledge and correspondingly higher levels of transfer. The theoretical implications of the findings are discussed in terms of the declarative/procedural and the episodic/semantic memory distinction. It is suggested that memory-impaired patients are capable of acquiring new semantic information although not at a normal rate. Implications for memory rehabilitation are also outlined.

Acquisition and transfer of declarative and procedural knowledge by memory-impaired patients: a computer data-entry task.

Previous research demonstrated that a single amnesic patient could acquire complex knowledge and processes required for the performance of a computer data-entry task. The present study extends the earlier work to a larger group of brain-damaged patients with memory disorders of varying severity and of various etiologies and with other accompanying cognitive deficits. All patients were able to learn both the data-entry procedures and the factual information associated with the task. Declarative knowledge was acquired by patients at a much slower rate than normal whereas procedural learning proceeded at approximately the same rate in patients and control subjects. Patients also showed evidence of transfer of declarative knowledge to the procedural task, as well as transfer of the data-entry procedures across changes in materials.

Extending the limits of complex learning in organic amnesia: computer training in a vocational domain.

This study explored the limits of learning that could be achieved by an amnesic patient in a complex real-world domain. Using a cuing procedure known as the method of vanishing cues, a severely amnesic encephalitic patient was taught over 250 discrete pieces of new information concerning the rules and procedures for performing a task involving data entry into a computer. Subsequently, she was able to use this acquired knowledge to perform the task accurately and efficiently in the workplace. These results suggest that amnesic patients' preserved learning abilities can be extended well beyond what has been reported previously.

Long-term retention of computer learning by patients with memory disorders.

Previous research has demonstrated that patients with memory disorders resulting from closed-head injury can acquire the complex knowledge and skills necessary for the use of a microcomputer. The present paper extends the generality of those findings by showing that (1) amnesic patients with other etiologies could similarly learn how to operate a computer and (2) the knowledge and skills acquired were retained over intervals of up to 9 months.

When priming persists: long-lasting implicit memory for a single episode in amnesic patients.

This experiment investigated the durability of implicit memory for a single episode in normal and amnesic subjects. The target materials consisted of sentence puzzles that were difficult to comprehend in the absence of a key word or phrase. Sentences were re-presented at delays ranging from one minute to one week, and implicit memory was indicated by facilitation in solving previously incomprehensible sentences on subsequent exposures. Patients with severe memory impairments on tests of explicit recall and recognition showed substantial and robust facilitation, or priming, from a single prior presentation and there was no evidence of a systematic decay of facilitation over retention intervals up to one week. The long-lasting implicit memory observed in the sentence puzzle task contrasts with previous findings of rapid decay of priming effects in amnesic patients.

Learning and retention of computer-related vocabulary in memory-impaired patients: method of vanishing cues.

Several investigators have suggested that microcomputers might serve as useful external aids for memory-impaired patients. However, knowledge of basic computer vocabulary may be necessary for patients to use and benefit from a microcomputer. The present paper describes a procedure, the method of vanishing cues, which facilitated the acquisition of computer-related vocabulary in four memory-impaired patients. The method involves the systematic reduction of letter fragments of to-be-learned words across trials. Although learning was slow and strongly dependent on first-letter cues, all patients acquired a substantial amount of the vocabulary and eventually were able to produce the target words in the absence of fragment cues. Further, they retained the vocabulary over a 6-week interval and showed some transfer of the knowledge they had acquired. These findings suggest that memory-impaired patients may eventually be able to use a microcomputer as a prosthetic device.

Computer learning by memory-impaired patients: acquisition and retention of complex knowledge.

Several investigators have shown that memory-impaired patients are capable of learning relatively simple information in both the laboratory and everyday life. The present research explored whether patients with memory disorders could also acquire complex knowledge--the domain-specific knowledge needed for operating and interacting with a microcomputer. The results indicated that patients with memory disorders of varying severity could learn to manipulate information on the computer screen, to write, edit and execute simple computer programs, and to perform disk storage and retrieval operations. The learning process, however, was slow relative to controls and the knowledge acquired appeared to be qualitatively different. Theoretical and practical implications of these findings are discussed.