Entorhinal cortex volume is associated with episodic memory related brain activation in normal aging and amnesic mild cognitive impairment

The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI.Illinois. Department of Public HealthNational Institute on Aging (Grant P01 AG09466)National Institute on Aging (Grant P30 AG10161)National Institute on Aging (Grant R01 AG017917)National Institute on Aging (Grant T32 AG000257

Neural correlates of impaired cognitive processes underlying self-unawareness in Alzheimer’s disease

peer reviewe

Functional cerebral changes in multiple sclerosis patients during an autobiographical memory test.

Our aim was to investigate the functional underpinnings of autobiographical memory (AM) impairment in multiple sclerosis (MS) patients. To that end, 18 patients and 18 controls underwent the autobiographical interview (AI). Subsequently, the 36 participants underwent a functional magnetic resonance imaging (fMRI) session designed to assess the construction and elaboration of AMs. A categorical control task was also presented. Patients were trained in the fMRI procedure to optimise the procedural aspects accompanying the task itself. Although the patients obtained significantly poorer AI scores (p < .001), their performance on the easier AM fMRI task was efficiently carried out, allowing relevant comparisons with healthy controls. Relatively to healthy controls, the patients showed increased and bilateral cerebral activations (p < .005) during the construction and elaboration phases. The prefrontal, temporal and posterior cerebral region activations were located within the core network sustaining AM, with the bilateral prefrontal region being centrally involved. The parametric neural responses to the difficulty of access and amount of details of memories were also significantly different for the two groups, with the right hippocampal region showing a particularly increased recruitment (p < .005). The findings suggested the presence of functional cerebral changes during AM performance and supported the presence of AM retrieval deficit in MS patients.journal articleresearch support, non-u.s. gov't20152014 09 22importe

The Role of Stress, Glucocorticoids & β-Adrenergic Signaling in Aversive, Hippocampus-Dependent Memory Retrieval

Studies in wild-type rats and mice, and mutant mice lacking norepinephrine (NE) demonstrate that NE, β1-adrenergic, cAMP/PKA and Epac signaling are required for intermediate-term hippocampus-dependent memory retrieval. Although it has been proposed that glucocorticoids (GCs) facilitate β-adrenergic signaling to impair retrieval, neither a specific requirement for NE nor a definitive mechanism as to how this interaction occurs has been established. This thesis provides compelling evidence that 1) GCs do not require (but can synergize with) the adrenergic system to impair hippocampus-dependent memory retrieval; 2) GCs and xamoterol interact with the β2 receptor to impair retrieval; 3) β2 receptors signal through Gi/o in the hippocampus to impair retrieval, acting to negate the facilitation of hippocampus-dependent memory retrieval mediated by β1-Gs signaling; 4) GCs impair retrieval through possibly direct interaction with the β2 receptor; 5) β2 signaling is required for retrieval and may be required for short-term maintenance of fear memory; 6) β3 signaling influences retrieval; 7) interactions between β receptors are important and net effects of β receptor stimulation (or antagonism) on hippocampal cAMP signaling likely determine the degree of retrieval impairment expressed, as individual β receptors can have similar or opposing effects on cAMP levels; and 8) adrenergic and glucocorticoid influences on retrieval are limited by the age of the memory

Sintomatologia depressiva e memória autobiográfica em pessoas idosas com demência de Alzheimer nas fases leve e moderada

A demência de Alzheimer é um quadro clinico que afeta um número crescente de pessoas idosas a que aparece, frequentemente, associada a sintomatologia depressiva. As alterações cognitivas relacionadas com a demência abrangem sobretudo a recuperação de memórias autobiográficas que, nos casos de sintomatologia depressiva, tendem a ser gerais e negativas. Pretende-se com este estudo avaliar os níveis de sintomatologia depressiva e a abrangência de memórias autobiográficas em pessoas idosas com demência de Alzheimer, assim como analisar a relação entre o tipo de memórias recuperadas e a sintomatologia depressiva. Participaram nesta investigação 40 pessoas idosas que se encontram na fase leve e moderada da demência de Alzheimer, com idades compreendidas entre os 63 e os 92 anos. Os resultados obtidos evidenciam que a maioria dos participantes (72,5%;29) apresenta sintomatologia depressiva, sendo as pessoas idosas na fase leve da demência aquelas que apresentam valores mais elevados (M=14,56; DP=6,06), embora os resultados não sejam estatisticamente significativos (U=-1,64; p>0,05). A análise dos resultados indica, também, um maior número de memórias autobiográficas gerais (M=8,78; DP=2,21) do que específicas (M=6,00; DP=2,31). Constata-se uma correlação negativa muito fraca e estatisticamente não significativa entre a sintomatologia depressiva e as memórias autobiográficas gerais (r=-0,207; p>0,01) e uma correlação positiva muito fraca e estatisticamente não significativa entre a sintomatologia depressiva e as memórias específicas (r=0,188; p>0,01). Os resultados indicam ainda uma correlação negativa moderada e estatisticamente significativa entre a sintomatologia depressiva e as memórias positivas recuperadas (r=-0,416; p<0,01) e uma correlação positiva moderada e estatisticamente muito significativa relativamente às memórias autobiográficas negativas (r=0,538; p<0,001). Este estudo alerta para a possibilidade de existência de sintomatologia depressiva associada a quadros demenciais e para a existência de mais memórias autobiográficas gerais do que específicas.Alzheimer's disease is a clinical condition that affects a growing number of old people to whom is, frequently, associated with depressive symptoms. The cognitive changes related to dementia include mainly the autobiographical memories retrieval that, in the cases of depressive symptomatology, tend to be general and negative. This study aims to assess the levels of depressive symptomatology and the range of autobiographical memories in old people with dementia in Alzheimer's disease, as well as to analyse the relationship between the type of recovered memories and depressive symptomatology. 40 elderly people who are in light and moderate stage of Alzheimer's dementia, aged 63 and 92 years old, participated in this research. The results obtained show that the majority of participants (72.5%;29) present depressive symptomatology, being elderly people in light phase of dementia, those who have higher values (M=14.56; DP=6.06), although the results are not statistically significant (U=- 1.64; p>0.05). The analysis of the results indicates, as well, a larger number of autobiographical memories (M=8.78; DP=2.21) than specific (M=6.00; DP=2.31). There is a very weak negative correlation and statistically not significant difference between depressive symptomatology and general autobiographical memories (r=-0.207; p>0.01) and a very weak positive correlation and statistically not significant difference between depressive symptomatology and specific memories (r=0.188; p>0.01). The results indicate a moderate and statistically significant negative correlation between the depressive symptomatology and the positive memories recovered (r=-0.416; p<0.01) and a moderate positive correlation and statistically very significant with regard to negative autobiographical memories (r=0.538; p<0.001). This study draws attention to the possibility of existence of depressive symptoms associated with dementia clinical condition and to the existence of more general than specific autobiographical memories

Cognitive and neural mechanisms of sense of self in neurodegenerative disorders

The ability to maintain a coherent and continuous ‘sense of self’ is a fundamental component of being human, enabling us to interact and function successfully in everyday life. While a sense of self is commonly accepted to involve both ‘extended’ (i.e., memories) and ‘interpersonal’ (i.e., social) elements, the precise cognitive and neural mechanisms underlying these aspects of the self remain poorly understood. This thesis draws upon theory and methods from contemporary cognitive neuroscience to examine the neurocognitive underpinnings of the extended and interpersonal self in Alzheimer’s disease (AD), semantic dementia (SD), and the behavioural variant of frontotemporal dementia (bvFTD): neurodegenerative disorders involving progressive cognitive and behavioural change as the result of degeneration to distinct brain networks. Employing a novel experimental method (the ‘NExt’ taxonomy), Part 1 of the thesis (Chapters 3 and 4) reveals how a full spectrum of episodic and semantic memory representations may be drawn upon to support one’s past and future life stories, giving rise to a sense of continuity of the extended self. Part 2 (Chapters 5 and 6) illustrates how the complex social interactions that comprise the interpersonal self may be deconstructed into several distinct, yet interacting, psychological components. Furthermore, neuroimaging analyses uncover widespread neural regions to be associated with both the extended and interpersonal aspects of the self, incorporating brain networks beyond those typically implicated in self-related processing. The improved neurocognitive characterisation of the self provided by this thesis highlights the complex, multifaceted nature of this construct. Moreover, from a clinical perspective, distinct profiles of the self unveiled across AD, SD, and bvFTD reveal how ultimately, ‘all is not lost’ in neurodegeneration

Music and autobiographical memory: how an analysis of Desert Island Discs may help conceptualise personalised music interventions for people living with dementia

Dementia disrupts the autobiographical memory system, including memories of specific episodes, personal experiences, and the facts of one’s life. All these elements contribute to a sense of self. Disruption of autobiographical memory can affect psychological well-being, potentially contributing to psychological and behavioural symptoms and compromised interpersonal communication. This study explores how autobiographical memory functioning in people living with dementia can be engaged through personalised music interventions, thus optimising such interventions and potentially improving dementia care. Three main methods are used: 1) A synthesis of two systematic reviews: the first focused on how autobiographical memory is affected across the different types of dementia; the second explored the effect of personalised music on behavioural and psychological symptoms in patients with dementia. The first systematic review (28 papers) found differences among the subtypes of dementia in relation to the temporal gradient effect, the recalled details of semantic and episodic memories and the recall of self-defining memories. The second systematic review (30 studies) found a positive but not lasting effect on behavioural and psychological symptoms. The effect was greater in active personalised music interventions than in passive listening to personalised music 2) A qualitative thematic analysis of the Desert Island Discs radio broadcasts, to understand the processes of sharing personally meaningful music choices and how music supports a sense of self. The analysis identified the emotional dimensions of autobiographical music memories; of particular salience was that of nostalgia and how music enables people to share meaningful emotional autobiographical memories, including painful and difficult ones. 3) An exploratory focus group discussion with professionals who use music interventions with people living with dementia, to contribute to theoretical conceptualization for personalised music intervention. The analysis demonstrated how music enables emotions, especially during difficult experiences; it also highlighted the importance of each person’s history and the need to find complementary ways to evaluate music interventions in dementia care

Spatial language abilities and cognition across the adult-lifespan and in early alzheimer’s disease

Space constitutes one of the core framing structures of experience in the natural environment. Therefore, communicating spatial information with verbal means, such as locative relations between objects, is vital for numerous everyday activities and constitutes a core part of human linguistic communication. The present project aimed to 1) develop psychometrically sound measures assessing spatial language abilities, including naming static and dynamic spatial relations, memory for route- and survey-based descriptions, and comprehension of descriptions of locative relations under different spatial reference frames; 2) identify the trajectories of these spatial language abilities across the adult-lifespan and contrast them against trajectories of various (non-verbal) visuospatial and (non-spatial) verbal abilities; and 3) investigate spatial language abilities in individuals who are at an early stage of Alzheimer’s disease (AD), for the first time. Across a series of studies involving 160 adults aged between 18 and 85, we found comparable age-related declines in spatial language and visuospatial abilities, although their onset and magnitude depended on the type of subability examined. By contrast, verbal abilities remained well-preserved with increasing age. Moreover, performance in spatial language measures was found to discriminate mild AD patients and age-, education-, and gender-matched controls to a very high degree. The results of the present work have several theoretical and practical implications, as they 1) establish the test-retest reliability, and the concurrent, construct and discriminative validity of the newly-developed spatial language measures; 2) reveal a number of divergent and convergent domain-specific cognitive changes across the adult-lifespan; 3) extend the large existing literature on the detrimental (a)typical ageing effects on visuospatial cognition by demonstrating that spatial processing is also compromised when assessed through language; and 4) suggest that language- and perception-based representations of space are underpinned by comparable cognitive operations and supported by overlapping neural networks that are particularly sensitive to ageing effects

Autobiographical memory retrieval in patients with Alzheimer's disease

Item does not contain fulltextWith aging, the content of self-reported autobiographical memories shifts from episodic to semantic. Onset of Alzheimer's disease enhances this pattern, but the neural underpinnings of this change in Autobiographical Memory (AM), in particular the role of hippocampal degradation, are unknown. We employed fMRI contrasting autobiographical and semantic retrieval, in 22 healthy elderly and 21 Alzheimer's patients. The shift towards semantic characteristics in AM retrieval was indeed enhanced in patients. Both groups activated brain regions commonly involved in AM retrieval, including occipital association areas, medial temporal lobes, lateral temporal and midline prefrontal areas. When compared to controls, Alzheimer's patients showed enhanced activity in the left inferior frontal gyms (LIFG), ventromedial prefrontal cortex (vmPFC), right precuneus and left lingual gyrus. Activation of LIFG and vmPFC was significantly negatively correlated with hippocampal volume in patients only. Thus, we speculate that the linking function of the degraded hippocampus is taken over by the vmPFC: a shift recently observed during normal consolidation. This potentially compensatory process may support early Alzheimer's detection or prognosis