Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer’s disease

Structural stability and change in semantic and episodic memory performance as well as interindividual differences in 5-year changes in these constructs are examined within a sample of older adults (age rangeT1 = 60-80; n = 361). Interindividual differences in change were limited but significant. Stability coefficients were higher for semantic memory (.95) than for episodic memory (.87). Changes in episodic and semantic memory performance were strongly associated (r =.68). Across time, variances and covariances increased, and a tendency toward dedifferentiation in terms of increasing correlations was found. Chronological age was related to both level and change, but gender and education were only related to level of memory performance. Collectively, these results depict relatively high degrees of structural stability and stability of interindividual differences in declarative memory in old age.

BackgroundModified Dead‐Alive Test (M‐DAT), which was developed and validated by Ozel‐Kizil et. al. (2018) evaluates semantic and episodic memory together. The original form was developed by Kapur et al. (1989), however it was not adequately studied.MethodM‐DAT consists of 45 names of celebrities who had died in remote past (15), died in the last five years (15) and who are still alive (15) and participants are asked whether they are alive or dead. Correct number of items concerning celebrities who died in remote past gives the semantic memory performance, while half of the the sum of correct number of items concerning celebrities who are still alive and had died in the last five years is accepted as episodic memory performance. Semantic and episodic memory performances of patients with DSM‐5 major neurocognitive disorder due to Alzheimer’s Disease‐MND‐AD (n=69), patients with DSM‐5 minor neurocognitive disorder‐MiND (n=27) who were admitted to geriatric psychiatry clinic and volunteered healthy controls‐HC (n=29) were compared. The groups were compared either by one‐way ANOVA or Kruskal‐Wallis tests and Bonferroni or Mann Whitney U tests was used for post‐hoc analysis.ResultMND‐AD group was older and less educated. Also MND‐AD group had lower MMSE scores while MiND and HCs had similar scores. MND‐AD had lower semantic and episodic scores than MiND and HC, also the scores of MiND group were lower than HCs. Both M‐DAT semantic and episodic scores were positively correlated with education in the whole sample (R=.53, p<0.001; R=.43, p<0.001). Although semantic memory performances were higher than episodic memory performances in all groups, two scores were positively correlated (R=.71, p<0.001).ConclusionThe results of the study suggested a semantic memory impairment as well as episodic memory deficit in patients with major and minor neurocognitive disorder. Although previous studies have conflicting results, semantic memory deficit early in Alzheimer’s disease and in mild cognitive impairment was also reported (3). M‐DAT is an alternative for the assessment of semantic memory that is usually evaluated by verbal fluency tests. Evaluating episodic and semantic memory together is an important advantage however M‐DAT is affected by education and the items require updating.

Nature of personal semantic memory: evidence from Alzheimer’s disease

As part of a unifying theory of autism, Ben Shalom (2009) proposed that while procedural, perceptual and semantic memory functions are intact in Autism Spectrum Disorder (ASD), the more integrative level of episodic memory is impaired. According to Ben Shalom, this reduced integration may be due to the reduced function of the medial prefrontal cortex (mPFC), which may also explain the reduced integration found in motor, sensory-perceptual and emotional processes in ASD. The present review examines this hypothesis, by focusing on evidence regarding autobiographical memory (AM) episodes in ASD—arguably the highest form of memory integration processes. Most research on memory in ASD thus far has focused on memory for experimentally-presented stimuli (Lind, 2010; Boucher et al., 2012). The present paper builds on this literature to examine the rich evidence that has recently accumulated from in-depth, systematic studies of AM in ASD—memories of personally-related events that are naturalistically accumulated over a person's lifetime. Of note, research on AM is limited in its focus on memories that cannot be as readily verified (but see Bruck et al., 2007), and in its reliance on high-functioning verbal individuals. Nonetheless, studies of AM provide us with an unparalleled perspective on the naturalistic process of memory integration in ASD. Specifically, this review aims to determine how well memory episodes are integrated in ASD; which elements become integrated and which do not; whether the ability to form integrated, episodic memories relates to other cognitive and emotional capacities; and how this pattern of integration changes over time. Semantic and episodic autobiographical memory (AM) The declarative memory system comprises semantic and episodic components. Semantic memories are memories of timeless, de-contextualized facts. Episodic memory refers to personal events recollected in the context of a particular time and place, with some reference to oneself as a participant in the episode (Tulving, 2002). Thus, episodic memories involve two functions: the ability to bind different perceptual elements; and, in humans, the ability to perceive of oneself within this context. On a neurobiological level, episodic memory storage and retrieval are thought to involve the interaction of cortical association areas, in which basic sensory information regarding what occurred and where is stored; the hippocampus, which binds these elements into cohesive memories of individual events; and the mPFC, which further contextualizes these events into schemas, such as the self (Preston and Eichenbaum, 2013). AM refers to memory for information pertaining to the self; and while it is often viewed as overlapping with episodic memory, the two are not synonymous (Gilboa, 2004). Episodic memory is a memory system, while AM is a type of content (Gardiner, 2008). Thus, episodic memory functions can encompass both AM and simple phenomena that do not necessarily represent self-relevant information (e.g., source memory). At the same time, AM in fact comprises of both semantic and episodic knowledge (e.g., semantic knowledge of one's date of birth, alongside an episodic memory of one's last birthday). In children with ASD, both semantic and episodic AM is reduced (Bruck et al., 2007; Bon et al., 2012; Goddard et al., 2014), though by adulthood, adults with ASD show a spared memory for semantic AM, alongside reduced episodic AM (Klein et al., 1999; Crane and Goddard, 2008). These studies suggest that as semantic AM may grow in ASD, episodic AM impairments are pervasive. These results fit with the general memory profile in ASD, viz., spared semantic memory alongside difficulties with episodic memory, which is found across experimental studies (Boucher and Bowler, 2008). The present review concerns itself primarily with episodic AM in ASD, though semantic memory will be discussed as it relates to the content of autobiographical narratives.

BackgroundSubjective memory concerns are relatively easy to assess and are useful if they can identify people with cognitive deficits or can predict cognitive decline. In a multiethnic cohort of oldest‐old individuals, we studied whether baseline cognitive performance and cognitive decline differ between individuals who report memory concerns and those who do not.Method LifeAfter90 participants are long‐time members of the Kaiser Permanente Northern California Health Care System without a dementia diagnosis in their medical record at recruitment. Evaluations are every six months and include the Spanish and English Neuropsychological Assessment Scales (SENAS), which assesses episodic memory, semantic memory, and executive function domains. At baseline, participants answered the question ‘Are you concerned that you have a memory or other thinking problem?’ Using linear mixed models with random intercepts, we estimated the baseline and longitudinal association of memory concerns with each SENAS domain. The models used years since baseline as the time variable, and adjusted for baseline age, sex, race/ethnicity, education, and practice effects. Potential differences in cognitive decline by presence or absence of memory concerns were assessed with an interaction term (memory concerns*time).ResultAt baseline, the 665 participants were on average 92.8 years of age, 62% were women, 34% were college graduates, 69% were racial/ethnic minorities, and 40% reported memory concerns (Table 1). The average follow‐up was 0.9 years (range: 0‐1.9). Memory concerns were associated with worse baseline performance in episodic memory (ß=‐0.21) and executive function (ß=‐0.12) but not semantic memory (ß=‐0.01) (Figure & Table 2). Although cognitive scores decreased over time for semantic memory (ß=‐0.31) and executive function (ß=‐0.10), the decline did not differ between people with and without memory concerns (Figure & Table 2).ConclusionIn this multi‐ethnic oldest‐old cohort, individuals with memory concerns have worse baseline cognitive performance in executive function and episodic memory, but their rate of decline is similar to individuals without memory concerns. Although memory concerns appear to identify individuals with objective cognitive impairment, it does not identify those who may decline faster. With additional follow‐up, we will continue to explore the utility of memory concerns in predicting future cognitive performance.

Semantic, episodic, and autobiographical memory in a postmeningitic amnesic patient

BackgroundDepression impacts 50% of the elderly population and is a risk factor for dementia but its prevalence and role in cognitive decline in Non‐Whites and the oldest‐old is unclear.MethodLifeAfter90 is a racially/ethnically diverse cohort of individuals aged 90+ that launched in 2018 with the aim of characterizing cognitive and brain aging after the 9th decade of life. Participants are members of an integrated healthcare delivery system without a dementia diagnosis in their medical record at recruitment. Depression at baseline was evaluated with the Global Depression Scale (GDS) and defined as GDS>4. Cognitive testing every 6 months uses the Spanish and English Neuropsychological Assessment Scales (SENAS), to assess cognitive domains of episodic memory, semantic memory, and executive function. Linear mixed models with random intercepts, evaluated the baseline and longitudinal association of depression with each SENAS domain. The models used years since baseline as the time variable, and adjusted for baseline age, sex, race/ethnicity, education, and practice effects. An interaction term (depression*time) tested for differences in decline in cognitive domains by baseline depression status.ResultOf 655 participants 32% are White, 22% Asian, 22% Black, 15% Latino, and 8% Other/Multiracial. 35% had <high school education, 38% were male, and mean age was 93 years. At baseline, 32% were classified as having depression with the highest prevalence among Latinos and those with <high school education (Table 1). The average follow‐up was 0.9 years (range: 0‐1.9). Depression was associated with poorer semantic memory (ß=‐0.17) and executive function (ß=‐0.18) but not with episodic memory (Table 2). Semantic memory (ß=‐0.28) and executive function (ß=‐0.11) decreased over time, however episodic memory did not. The semantic memory and executive function decline did not differ by depression (Figure 1 & Table 2).ConclusionDepression impacts one third of this ethnically diverse cohort of oldest‐old individuals and ais more prevalent in Latino participants. While depression is associated with poorer baseline semantic memory and executive function; it is not associated with episodic memory, nor is it associated with greater cognitive decline. These results suggest that while depression may impact cognitive performance it may not impact cognitive change in those aged 90+.

Episodic and semantic memory in children with mesial temporal sclerosis

Structural equation modeling was used to investigate whether age-related episodic and semantic memory impairments are better explained by decline in processing speed or executive functioning (or both), rather than directly in terms of memory components. The models tested were based on an extensive review of the literature on cognitive decline in normal aging, up to very old age. A computerized test battery, measuring episodic memory (free and cued recall; recognition), semantic memory (fluency; naming accuracy and latencies), processing speed and executive functioning, was administered to 234 elderly persons ranging from young-old to very old age (55–96 years). To avoid large variance in response times due to physical instead of cognitive limitations, no motor responses were required from participants. Age-related decline in episodic and semantic memory performance was found to be the consequence of declines in processing speed and executive functioning. Processing speed mainly mediated decline of...

BackgroundElevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population.MethodsWe linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method.ResultsA higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = −0.08, 95% CI −0.14; −0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity.ConclusionsThis indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

Previous research has shown memory deficits in obsessive–compulsive disorder (OCD) but has been inconsistent as to which aspects of memory are affected and how deficits are linked to OCD symptoms. The current study assessed working, episodic and semantic memory in 19 subjects with OCD and 19 matched controls. The severity of OCD symptoms was assessed using a clinician-rated scale (Yale-Brown Obsessive–Compulsive Scale, Y-BOCS) and a self-report measure (Padua Inventory-Revised, PI-R). Episodic and semantic memory performance was significantly reduced in OCD subjects relative to controls while working memory was preserved. Episodic memory performance in both OCD and healthy control subjects was significantly related to the Padua dimensions Rumination and Checking even if the influence of depressive mood and total OC symptom severity was controlled for. Linear regression revealed that Rumination was most closely related to episodic memory performance in both OCD and healthy control subjects above Checking. Results point to the possible impact of self-focused attention on effortful encoding processes.

Pathological tau is suggested to play a role in cognitive deterioration in the preclinical phase of Alzheimer’s disease. We investigated cross-sectional associations of tau burden with episodic and semantic memory performance in older adults without dementia. A systematic search in MEDLINE (via PubMed), PsychINFO, and Embase resulted in 24 eligible studies for meta-analysis. Tau burden was assessed using CSF, PET, or histopathological measures. All studies evaluated associations of tau with episodic memory: weighted effect sizes were -0.46 (95 % CI [-0.73; -0.20], p < .001) for episodic composite scores, -0.19 ([-0.36; -0.03], p = .024) for delayed word list recall, and -0.05 ([-0.14; 0.04], p = .257) for logical memory. Fourteen studies evaluated associations of tau with semantic memory: weighted effect sizes were -0.28 ([-0.52; -0.04], p = .023) for semantic composite scores, -0.06 ([-0.16; 0.03], p = .194) for semantic fluency, and 0.06 ([-0.06; 0.18], p = .319) for picture naming. Our findings indicate that tau burden related to both episodic and semantic memory impairment in older individuals without a diagnosis of mild cognitive impairment or manifest dementia, with episodic composite scores showing the strongest association with tau burden. Future potential lies in developing more sensitive scores to detect this subtle cognitive impairment, which could contribute to early identification of individuals in the preclinical phase of Alzheimer’s disease, thereby improving early diagnosis and timely intervention.

Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the diagnostic criteria for posterior cortical atrophy and eight for logopenic variant primary progressive aphasia. All participants underwent 3 T magnetic resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV-1451) positron emission tomography, and episodic and semantic memory, language, executive and visuospatial functions assessment. Raw cognitive scores were converted to age-adjusted Z-scores (W-scores) and averaged to compute composite scores for each cognitive domain. Independent regressions were performed between 18F-AV-1451 binding and each cognitive domain, and we used the Biological Parametric Mapping toolbox to further control for local grey matter volumes, 11C-PiB uptake, or both. Partial correlations and causal mediation analyses (mediation R package) were then performed in brain regions showing an association between cognition and both 18F-AV-1451 uptake and grey matter volume. Our results showed that decreased cognitive performance in each domain was related to increased 18F-AV-1451 binding in specific brain regions conforming to established brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and angular gyrus; semantic memory: left anterior temporal regions; language: left posterior superior temporal lobe and supramarginal gyrus; executive functions: bilateral frontoparietal regions; visuospatial functions: right more than left occipitotemporal regions). This pattern of regional associations remained essentially unchanged-although less spatially extended-when grey matter volume or 11C-PiB uptake maps were added as covariates. Mediation analyses revealed both direct and grey matter-mediated effects of 18F-AV-1451 uptake on cognitive performance. Together, these results show that tau pathology is related in a region-specific manner to cognitive impairment in Alzheimer's disease. These regional relationships are weakly related to amyloid burden, but are in part mediated by grey matter volumes. This suggests that tau pathology may lead to cognitive deficits through a variety of mechanisms, including, but not restricted to, grey matter loss. These results might have implications for future therapeutic trials targeting tau pathology.

Individuals with mild cognitive impairment (MCI) can often progress into Alzheimer’s Disease (AD). Research suggests that decline in episodic memory and semantic memory, as well as functional abilities, can be sensitive in predicting disease progression. This study aimed to (a) investigate episodic and semantic memory performance differences between AD and MCI, (b) determine if memory performance predicts observation-based activities of daily living (ADLs), and (c) explore whether semantic memory mediates the relationship between episodic memory and ADLs. Fifty-eight AD, 53 MCI, and 72 healthy control participants were administered the Rey-O, California Verbal Learning Test, Animal Fluency Test, Boston Naming Test, and Direct Assessment of Functional Status (DAFS). The results revealed, first, that AD participants performed significantly lower than the MCI participants across semantic memory and episodic memory tasks, with the exception of the Boston Naming Test. Second, hierarchical-stepwise regression analyses found that semantic memory significantly predicted DAFS orientation, communication, and financial skills in AD, but episodic memory predicted shopping skills. Furthermore, semantic memory significantly predicted DAFS transportation skills in AD and MCI. Third, within the overall sample, semantic memory mediated the relationship between episodic memory and ADLs. Taken together, the findings suggest decline in semantic memory (as measured by confrontational naming and category fluency) and episodic memory (as measured by list and complex visual design learning and recall) may lead to decline in different and specific aspects of functional abilities in AD and MCI.

This study examined age differences in episodic memory, semantic memory, and priming using a random sample of 1,000 men and women from 10 age groups (35, 40, 45, . . . 80 years). The main purpose was to determine whether an age effect existed after differences on various demographic, intellectual, and biological factors had been controlled for. The simple correlations of age with episodic and semantic memory performance were found to be significant, whereas no relationship was found between age and levels of priming. After controlling for differences on the background factors, age predicted episodic but not semantic memory performance. It is proposed that the failure to account for the age effect on episodic memory is because it is caused by age-related neuronal changes.