Face-name Pairs Research Articles

Face masks degrade our ability to remember face-name associations more than predicted by judgments of learning

ABSTRACT In response to the COVID-19 pandemic, face masks became required attire. Face masks obstruct the bottom portion of faces, restricting face processing. The present study examined the influence face masks have on memory predictions and memory performance for new face-name associations. Participants studied face-name pairs presented for 8 s (Experiment 1) or 10 s (Experiment 2). Half of the face-name pairs included a face mask obstructing the nose and mouth of the pictured face, counterbalanced across participants. Participants provided item-by-item judgements of learning (JOLs) and completed subsequent cued recall and associative recognition memory tests. Both experiments demonstrated that face masks impaired memory for newly-learned names, however, the magnitude of the mask impact was under-predicted by JOLs. The presence of a face mask negatively influenced memory performance to a greater degree than participants’ JOLs predicted. Results have implications for name learning during pandemics, as well as in settings where face masks are common (e.g., medical field).

Circadian- and wake-dependent influences on face-name memory in healthy men and women over 3 weeks of chronic sleep restriction

ObjectivesFacial recognition is one of the key functions of the human brain, and linking a face to a name is critical in many social and occupational settings. This study assessed circadian- and wake-dependent effects on face-name recognition in healthy adults. MethodsThirteen healthy adults (20-70years; 7 F) were studied in a 39-day inpatient protocol that included 3weeks of 28 hours forced desynchrony with sleep restriction (6.5:21.5 hours sleep:wake). Starting 3 hours after scheduled wake, 6 novel face-name pairs were presented every 4 waking hours; recognition was tested 2 hours later. Performance data were averaged across ∼4 hours circadian phase or time-awake bins. ResultsFace-name recognition deteriorated with increased time awake (p < .0001) and exhibited significant circadian variation (p < .0001), with worst performance shortly after the core temperature nadir. There was a significant interaction between sex and circadian phase (p = .0177), with women performing significantly better than men at all circadian phases except 60° and 120°. Women exhibited a significantly higher amplitude than men during the third week of forced desynchrony (p < .01). ConclusionsLike many other aspects of neurobehavioral performance, recalling face-name associations is impacted by both duration of time awake and circadian phase. These results have implications for face recognition testing in medical contexts, such as in testing for dementia, because performance may be impacted by sleep deficiency and the time of testing.

A novel face-name mnemonic discrimination task with naturalistic stimuli

Difficulty remembering faces and names is a common struggle for many people and gets more difficult as we age. Subtle changes in appearance from day to day, common facial characteristics across individuals, and overlap of names may contribute to the difficulty of learning face-name associations. Computational models suggest the hippocampus plays a key role in reducing interference across experiences with overlapping information by performing pattern separation, which enables us to encode similar experiences as distinct from one another. Thus, given the nature of overlapping features within face-name associative memory, hippocampal pattern separation may be an important underlying mechanism supporting this type of memory. Furthermore, cross-species approaches find that aging is associated with deficits in hippocampal pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation and provide a more sensitive measure of age-related cognitive decline compared to traditional memory tasks. However, traditional face-name associative memory tasks do not parametrically vary overlapping features of faces and names to tax hippocampal pattern separation and often lack naturalistic facial features (e.g., hair, accessories, similarity of features, emotional expressions). Here, we developed a face-name mnemonic discrimination task where we varied face stimuli by similarity, race, sex, and emotional expression as well as the similarity of name stimuli. We tested a sample of healthy young and older adults on this task and found that both age groups showed worsening performance as face-name interference increased. Overall, older adults struggled to remember faces and face-name pairs more than young adults. However, while young adults remembered emotional faces better than neutral faces, older adults selectively remembered positive faces. Thus, the use of a face-name association memory task designed with varying levels of face-name interference as well as the inclusion of naturalistic face stimuli across race, sex, and emotional expressions provides a more nuanced approach relative to traditional face-name association tasks toward understanding age-related changes in memory.

Perilesional and contralesional brain activations related to associative encoding of unfamiliar face-names pairs in adults with left chronic stroke with or without ischemic infarct on left inferior frontal gyrus

The study of an Ischemic stroke infarction allows verifying how the lesion produces alterations in the neuronal networks resulting in cognitive deficits. It also allows the verification of adaptive and maladaptive cerebral reorganization related to the injury. In our previous fMRI study, we found that patients without ischemic vascular lesions in left inferior frontal gyrus showed an efficient compensation mechanism during the associative encoding of face name pairs, by the increased activation of ventrolateral and dorsolateral areas of contralesional hemisphere associated with better memory performance. While patients with ischemic vascular lesions on left inferior frontal gyrus (IFG) demonstrated worse memory performance and no signs of compensation mechanism. The present study explores more of these findings by analyzing perilesional and contralesional activations related to unfamiliar face name associative encoding in adults with chronic ischemic stroke, with or without left IFG lesion, compared to healthy controls. The main results showed that stroke survivors without lesions in IFG demonstrated increased activation in perilesional and contralesional prefrontal regions associated with better associative memory recognition, which are indicative of adaptive compensatory mechanisms. However, they also showed a negative correlation between the activation of right anterior prefrontal and inferior parietal regions and the associative memory performance, which may indicate the presence of maladaptive interhemispheric disinhibition. On the other hand, stroke survivors with IFG lesions demonstrated negative correlations in activations of the ipsilesional inferior parietal cortex and positive correlations in activations of the left middle frontal gyrus and left precentral cortex, which demonstrate the simultaneous occurrence of adaptive and maladaptive brain reorganization mechanisms in this group. However, the increase in perilesional prefrontal regions, associated with bilateral activation of the hippocampus and amygdala, was not enough to compensate for the inefficiency of associative memory performance. Finally, the differences in activation observed in stroke survivors reflect their clinical heterogeneity and demonstrate that adaptive or maladaptive compensatory mechanisms can coexist in the same group of patients. Furthermore, they reinforce the importance of the left IFG in the associative encoding of unfamiliar face name pairs and may suggest a deficit in associative memory related to injury in this region.

Preservation of long-term memory in older adults using a spaced learning paradigm

How much information we retain depends on type/schedule of training. It has been widely acknowledged that spaced learning is advantageous compared to massed learning for cognitively healthy young adults and should be considered an educational standard. Literature would suggest that the spacing effect is preserved with age, though it is unclear whether this effect translates to more ecologically valid concepts such as face-name associations, which are particularly susceptible to deterioration with age. Two experiments were conducted to investigate the effects of spacing across recent/remote retention intervals, and the effect of age on spacing in cognitively healthy older adults using the Face-Name Pairs task. Experiment 1 results suggest that the beneficial memory effects of spacing are particularly observed with long-term memory. Experiment 2 results suggest that older adults are impaired at learning compared to younger adults, that the spacing effect influences both older and younger adults at longer intervals, and that spaced-trained participants display similar forgetting patterns at longer intervals, irrespective of age. These results may have some implications regarding improving the conditions under which optimum retention occurs (namely, whether spacing is beneficial when learning ecologically valid concepts at longer intervals outside of laboratory settings), and may provide insight into the effect of age on our ability to learn and remember face-name associations.

Improvement of episodic memory retention by a memory reactivation intervention across the lifespan: from younger adults to amnesic patients

Spontaneous reactivation of recently acquired memories is a fundamental mechanism of memory stabilization. Re-exposure to specific learned cues during sleep or awake states, namely targeted memory reactivation, has been shown to improve memory retention at long delays. Manipulation of memory reactivation could have potential clinical value in populations with memory deficits or cognitive decline. However, no previous study investigated a target memory reactivation approach on those populations. Here we tested the hypothesis that a reactivation-based intervention would improve episodic memory performance in healthy adults and amnestic patients. On Day 1, young adults, old adults and amnestic Mild Cognitive Impairment patients (n = 150) learned face-name pairs and 24 h later either received a reactivation intervention or a reactivation control (Day 2). On Day 3, associative and item memory were assessed. A robust Bayesian Generalized Mixed Model was implemented to estimate intervention effects on groups. Groups that underwent the reactivation-based intervention showed improved associative memory retention. Notably, amnestic patients benefited more from the intervention as they also had better item memory retention than controls. These findings support memory reactivation as stabilization and strengthening mechanism irrespectively of age and cognitive status, and provides proof-of-concept evidence that reactivation-based interventions could be implemented in the treatment and rehabilitation of populations with memory deficits.

Targeted memory reactivation of face-name learning depends on ample and undisturbed slow-wave sleep

Face memory, including the ability to recall a person’s name, is of major importance in social contexts. Like many other memory functions, it may rely on sleep. We investigated whether targeted memory reactivation during sleep could improve associative and perceptual aspects of face memory. Participants studied 80 face-name pairs, and then a subset of spoken names with associated background music was presented unobtrusively during a daytime nap. This manipulation preferentially improved name recall and face recognition for those reactivated face-name pairs, as modulated by two factors related to sleep quality; memory benefits were positively correlated with the duration of stage N3 sleep (slow-wave sleep) and negatively correlated with measures of sleep disruption. We conclude that (a) reactivation of specific face-name memories during sleep can strengthen these associations and the constituent memories, and that (b) the effectiveness of this reactivation depends on uninterrupted N3 sleep.

Facilitation effect of incidental environmental context on the computer screen for paired-associate learning.

Three experiments, in which a total of 198 undergraduates engaged, investigate whether the incidental environmental context on the computer screen influences paired-associate learning. Experiment 1 compared the learning of foreign- and native-language words between a constant context condition, where the stimulus and response pairs were presented twice on the same 5-s video background context, and a varied context condition, where the pairs were presented twice on different video contexts. Repetition in the same context resulted in better learning than in different contexts, evaluated with a paper-and-pencil test. Experiment 2 investigated learning of paired-associate foreign and native words in the same video contexts, or photograph contexts, or on a neutral grey background. Both the video and the photograph contexts equally facilitated the paired-associate learning compared with the grey background. Experiment 3 investigated whether the incidental environmental context similarly facilitated face-name paired-associate learning. We added a new condition of spot illustrations, and a second testing 1 day later. The repetition of face-name pairs within the same complex incidental environmental context on the computer screen (either video or photograph background) facilitated the paired-associate learning. There was no significant difference in learning performance between video and photograph background contexts, which were significantly better than grey or spot-illustration backgrounds which did not differ from each other. The retention interval did not interact with the effect of the background. The present results show that repetition within the same video or photograph context, covering the entire background of the video screen on which each item pair was superimposed, facilitates paired-associate learning.

Feeling-of-knowing experiences breed curiosity

ABSTRACT A central tenet in theoretical work on metacognition is that retrieval experiences during memory search can exert control over behaviour. States of curiosity, which reflect motivational tendencies to seek out information, may play a critical role in this control function. We conducted two experiments to address this idea, focusing on links between feeling-of knowing (FOK) experiences, memory-search duration, and subsequent information-seeking behaviour. We administered an episodic FOK paradigm that probed memory for previously studied face-name pairs, and subsequently provided an opportunity to select limited pairs for restudy. This set-up allowed us to test whether current search duration and subsequent restudy choices are biased towards items with high FOK ratings. Results revealed a positive relationship between FOK ratings and the response times of these judgements. We observed a similar positive relationship between FOK ratings and subsequent item selection for restudy. Moreover, experimental manipulations of FOK ratings based on familiarity of the face cues also had parallel effects. Our findings suggest that metacognitive experiences during unsuccessful retrieval from episodic memory can induce states of curiosity that shape behaviour beyond the immediate retrieval context. Curiosity may act as a bond to ensure that memory gaps identified through unsuccessful retrieval adaptively guide future learning.

The Effect of Memory Training on Memory Control Beliefs in Older Adults with Subjective Memory Complaints

ABSTRACT Objective: To study whether memory control beliefs predict response to memory training, or change as a result of participating in memory training. Methods: Eighty community based participants with subjective memory complaints Community-based study at UCLA were randomized to one of three conditions: Memory Training, the program consisted of weekly 120-minute classes featuring instruction in three specific strategies: Method of Loci; Chunking Technique; and Face-Name Association, Health Education or Wait-List over seven weeks. All participants underwent pre- and 1-week post-intervention follow-up memory testing for recalling word lists (in serial order and any order) and face-name pairs. Memory control beliefs were assessed at baseline and follow-up using the Memory Controllability Inventory, which consists of four subscales; Present Ability; Potential Improvement; Effort Utility; and Inevitable Decrement. Results: Sixty-three participants (mean age [SD] 68.3 [6.7] years) were included in the analysis. ANCOVA revealed significant group differences in the Present Ability subscale, F2,58 = 4.93, p =.01. Participants in the Memory Training group significantly improved on the Present Ability subscale compared to the Health Education group (mean difference =.96, SE =.31, p =.003, effect size = 0.93). From regression analyses, baseline Memory Controllability Inventory subscales did not significantly predict memory performance after memory training. Conclusions: Baseline memory control beliefs did not predict memory performance following the intervention, but participating in memory training enhanced memory control beliefs about current memory function. These results suggest that participating in memory training can enhance confidence in one’s memory ability.

I know your face but can't remember your name: Age-related differences in the FNAME-12NL.

ObjectiveThe Face-Name Associative Memory test (FNAME) has recently received attention as a test for early diagnosis of Alzheimer’s disease. So far, however, there has been no systematic investigation of the effects of aging. Here, we aimed to assess the extent to which the FNAME performance is modulated by normal ageing.MethodIn a first step, we adapted the FNAME material to the Dutch population. In a second step, younger (n = 29) and older adults (n = 29) were compared on recall and recognition performance.ResultsSignificant age effects on name recall were observed after the first exposure of new face-name pairs: younger adults remembered eight, whereas older adults remembered a mean of four out of twelve names. Although both age groups increased the number of recalled names with repeated face-name exposure, older adults did not catch up with the performance of the younger adults, and the age-effects remained stable. Despite of that, both age groups maintained their performance after a 30-min delay. Considering recognition, no age differences were demonstrated, and both age groups succeeded in the recognition of previously shown faces and names when presented along with distractors.ConclusionsThis study presents for the first time the results of different age groups regarding cross-modal associative memory performance on the FNAME. The recall age effects support the hypothesis of age-related differences in associative memory. To use the FNAME as an early cognitive biomarker, further subscales are suggested to increase sensitivity and specificity in the clinical context.

0117 Circadian- and Wake-Dependent Effects on Recall for Face-Name Pairs

Abstract Introduction The ability to remember the face and name of a person we have recently met is a critical skill often impacted by cognitive impairment and Alzheimer’s disease. We used a forced desynchrony protocol to explore whether recall of recently-learned face-name pairs is affected by time awake and/or circadian phase in healthy adults. Methods 13 healthy, cognitively normal adults (20-70yrs; 7F) participated in a 39-day inpatient protocol with 3 baseline days (10h time-in-bed/24h) and a 3-week forced desynchrony (FD) segment, where they lived on a 28-h day with sleep restriction (6.5h time-in-bed/28h, equivalent to 5.6h/24h). Core body temperature was collected throughout to estimate circadian period and phase. The face-name test was administered every 4h, beginning 3h after wake. Each test included a learning session with 6 novel face-name pairs. Recall was tested 2h later, when each face was presented twice in random order, once with a correct and once with an incorrect name. Participants were asked to respond whether each face-name pair was correct. Data were averaged across 4-h circadian phase or time awake bins and normalized as a percentage of each participant’s baseline performance. Results Face-name recall varied by time awake (p&amp;lt;0.05), with performance deteriorating ~12% over the course of 12h of wakefulness. Face-name recall also varied by circadian phase (p&amp;lt;0.05), with a ~10% difference in recall performance from the peak at circadian phase 240° (corresponding to the early biological evening) to the nadir at circadian phase 60° (corresponding to the early biological morning). Conclusion Both duration of prior wake and biological time of day impact the ability to correctly recall face-name pairs. Under normal entrained conditions, opposing circadian- and wake- dependent effects on memory for face-name associations may interact to produce stable performance across the day. Support Study supported by P01 AG009975 and conducted at Brigham and Women’s Hospital Center for Clinical Investigation, part of Harvard Clinical and Translational Science Center supported by UL1 TR001102. Authors supported by T32HL007901 and F32HL143893 (RKY); fellowships from the Novartis Foundation, the W.&amp;T. La-Roche Foundation, and Jazz Pharmaceuticals (MYM); a fellowship from the Natural Sciences and Engineering Research Council of Canada (SWC).

An Incidental Learning Method to Improve Face-Name Memory in Older Adults With Amnestic Mild Cognitive Impairment.

Forgetting names is a common memory concern for people with amnestic mild cognitive impairment (aMCI) and is related to explicit memory deficits and pathological changes in the medial temporal lobes at the early stages of Alzheimer's disease (AD). In the current experiment, we tested a unique method to improve memory for face-name associations in people with aMCI involving incidental rehearsal of face-name pairs. Older adults with aMCI and age- and education-matched controls learned 24 face-name pairs and were tested via immediate cued recall with faces as cues for associated names. During a 25- to 30-min retention interval, 10 of the face-name pairs reappeared as a quarter of the items on a seemingly unrelated 1-back task on faces, with the superimposed names irrelevant to the task. After the delay, surprise delayed cued recall and forced-choice associative recognition tests were administered for the face-name pairs. Both groups showed reduced forgetting of the names that repeated as distraction and enhanced recollection of these pairs. The results demonstrate that passive methods to prompt automatic retrieval of associations may hold promise as interventions for people with early signs of AD.

Diminished Learning Over Repeated Exposures (LORE) in preclinical Alzheimer's disease.

IntroductionWe determine whether diminished Learning Over Repeated Exposures (LORE) identifies subtle memory decrements in cognitively unimpaired (CU) older adults with Alzheimer's disease (AD) biomarker burden.MethodsNinety‐four CU participants (mean age = 77.6 ± 5.02) completed a challenging associative memory test, at home, monthly, for up to 1 year (mean = 9.97 months) on a study‐issued iPad. Learning curves for face‐name memory were computed for two versions completed monthly: same face‐name pairs (A‐A‐A) and alternate face‐name pairs (B‐C‐D). Positron emission tomography (PET) imaging characterized global amyloid (Pittsburgh Compound‐B (PiB); amyloid beta (Aβ)+/−) and regional tau burden (flortaucipir).ResultsDiminished LORE for same (but not alternate) face‐name pairs was associated with greater amyloid and tau burden. Aβ+/− group differences for same face‐name pairs emerged by the fourth exposure and was of medium‐to‐large magnitude (Cohen's d = 0.66; 95% confidence interval [CI] = 0.25‐1.08).DiscussionSubtle decrements in learning related to AD pathological burden in CU are detectable over short time‐intervals (ie, months). Implications for prevention trial design are discussed.

Validation of the Latin American Spanish version of the face-name associative memory exam in a Colombian Sample

Objective The Face-Name Associative Memory Exam (FNAME) has been used to detect subtle cognitive changes in clinically normal older adults at increased risk for Alzheimer’s disease. FNAME assesses learning and delayed recall for face-name pairs. The aim of this study is to introduce a Latin American Spanish version of the FNAME (LAS-FNAME), examine its psychometric properties, and provide preliminary normative data in a sample of clinically normal, Spanish-speaking individuals from Antioquia, Colombia. Method 59 clinically-normal individuals (71% females) were recruited by the Grupo de Neurociencias in Antioquia (Colombia). Age ranged from 27 to 82 years (M = 50.31, SD = 15.32) and years of education ranged from 2 to 17 years (M = 9.02, SD = 4.11). All participants completed the LAS-FNAME and a brief neuropsychological evaluation. We examined associations between age, education, and sex and performance on the LAS-FNAME. Internal consistency, convergent and discriminant validity were also assessed. Test-restest reliability was computed for a subset of participants (n = 32). Results LAS-FNAME exhibited moderate convergent validity with other memory measures (Free and Cued Selective Reminding Scale, r s=.465, p<.01; Wechsler Memory Scale III - Logical Memory Delayed Recall, r s=.479, p<.01). The subscales of the LAS-FNAME exhibited adequate internal consistency (α=.825). Test-retest reliability analyses demonstrated consistency of scores over time. Normative data was stratified by age (<50, 50–65, >65) and low and high educational attainment (≤8 and >8 years of education, respectively). Conclusions The LAS-FNAME is a valid and reliable measure to assess memory in clinically normal, Spanish-speaking individuals from Colombia for clinical and research purposes.

Effects of Mnemonic Strategy Training on Brain Activity and Cognitive Functioning of Left-Hemisphere Ischemic Stroke Patients.

Memory dysfunction is one of the main cognitive impairments caused by stroke, especially associative memory. Therefore, cognitive training, such as face-name mnemonic strategy training, could be an important intervention for this group of patients. The goal of this study was to evaluate the behavioral effects of face-name mnemonic strategy training, along with the neural substrate behind these effects, in the left frontoparietal lobe stroke patients. Volunteers underwent 2 sessions of functional magnetic resonance imaging (fMRI) during face-name association task: one prior and the other after the cognitive training. The fMRI followed a block design task with three active conditions: trained face-name pairs, untrained face-name pairs, and a couple of repeated face-name pairs. Prior to each fMRI session, volunteers underwent neuropsychological assessment. Training resulted in better performance on delayed memory scores of HVLT-R, and on recognition on a generalization strategy task, as well as better performance in the fMRI task. Also, trained face-name pairs presented higher activation after training in default-mode network regions, such as the posterior cingulate cortex, precuneus, and angular gyrus, as well as in lateral occipital and temporal regions. Similarly, untrained face-name pairs also showed a nonspecific training effect in the right superior parietal cortex, right supramarginal gyrus, anterior intraparietal sulcus, and lateral occipital cortex. A correlation between brain activation and task performance was also found in the angular gyrus, superior parietal cortex, anterior intraparietal sulcus, and lateral occipital cortex. In conclusion, these results suggest that face-name mnemonic strategy training has the potential to improve memory performance and to foster brain activation changes, by the recruitment of contralesional areas from default-mode, frontoparietal, and dorsal attention networks as a possible compensation mechanism.

Novel Face-Name Paired Associate Learning and Famous Face Recognition in Mild Cognitive Impairment: A Neuropsychological and Brain Volumetric Study

Purpose: To assess visual associative learning and famous face recognition ability among subjects with stable amnestic mild cognitive impairment (MCI) relative to early stage dementia due to Alzheimer’s disease (AD) and cognitively normal healthy controls (NC) and to correlate these differences with volumetric changes on MRI. Methods: A hospital-based cross-sectional observational study was conducted on 61 participants. The subjects underwent neuropsychological evaluation, including validated newly designed tests for novel face-name paired association learning recall and famous face recognition. MRI volumetry was done on a subset of patients to ascertain the topographical patterns of volume loss. Results: There were significant differences in performance on free recall for face-name paired associate learning in MCI (n = 22) compared to NC (n = 20) (p < 0.001) and MCI compared to AD (n = 19; p < 0.001). Significant differences were also noted in scores on the famous personalities test between MCI and NC (p = 0.007), and MCI and AD (p = 0.032). The free recall component of face-name pair associative learning significantly correlated with left cuneus (p = 0.005; r = 0.833) and right cuneus (p = 0.003; r = 0.861) volume in AD with no significant correlation among MCI and NC cohorts. Conclusions: Novel and semantically familiar face-name associative recalls are significantly impaired in MCI, and these potentially predate the MRI volumetric changes in MCI. Our findings expand the spectrum of recall deficits in MCI.

Associative Memory Impairments Are Associated With Functional Alterations Within the Memory Network in Schizophrenia Patients and Their Unaffected First-Degree Relatives: An fMRI Study.

Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness.

Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults

IntroductionMitochondrial dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). Accordingly, drugs that positively influence mitochondrial function are being evaluated in delay-of-onset clinical trials with at-risk individuals. Such ongoing clinical research can be advanced by developing a better understanding of how these drugs affect intermediate brain phenotypes associated with both AD risk and pathophysiology. MethodsUsing a randomized, parallel-group, placebo-controlled design in 55 healthy elderly volunteers, we explored the effects of oral, low-dose pioglitazone, a thiazolidinedione with promitochondrial effects, on hippocampal activity measured with functional magnetic resonance imaging during the encoding of novel face–name pairs. ResultsCompared with placebo, 0.6 mg of pioglitazone (but not 2.1 mg, 3.9 mg, or 6.0 mg) administered daily for 14 days was associated with significant increases in right hippocampal activation during encoding of novel face–name pairs at day 7 and day 14, relative to baseline. DiscussionOur exploratory analyses suggest that low-dose pioglitazone has measurable effects on mnemonic brain function associated with AD risk and pathophysiology.

Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults.

The ability to accurately judge memory efficiency (meta-memory monitoring) for newly learned (episodic) information, is decreased in older adults and even worse in Alzheimer's disease (AD), whereas no differences have been found for semantic meta-memory. The pathological substrates of this phenomenon are poorly understood. Here, we examine the association between meta-memory monitoring for episodic and semantic information to the two major proteinopathies in AD: amyloid (Aβ) and tau pathology in a group of cognitively unimpaired older adults. All participants underwent multi-tracer PET and meta-memory monitoring was assessed using a feeling-of-knowing (FOK) task for non-famous (episodic) and famous (semantic) face-name pairs. Whole brain voxel-wise correlations between meta-memory and PET data were conducted (controlling for memory), as well as confirmatory region-of-interest analyses. Participants had reduced episodic FOK compared to semantic FOK. Decreased episodic FOK was related to tauopathy in the medial temporal lobe regions, including the entorhinal cortex and temporal pole, whereas decreased semantic FOK was related to increased tau in regions associated with the semantic knowledge network. No association was found with Aβ-pathology. Alterations in the ability to accurately judge memory efficiency (in the absence of memory decline) may be a sensitive clinical indicator ofAD pathophysiology in thepre-symptomaticphase.