Laurie A. Miller

The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.

Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD— behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)—or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

Effects of Temporal Lobe Epilepsy on Retrograde Memory

Summary:  Purpose: In a previous investigation (Lah et al., 2004), we found deficits in retrograde memory in patients who had undergone temporal lobectomy (TL). In this study, we set out to determine whether such deficits are present before surgery in patients with temporal lobe epilepsy (TLE).

Memory for the past after temporal lobectomy: impact of epilepsy and cognitive variables

A few previous studies have revealed impairments in remote memory in patients with temporal lobe epilepsy, but many questions about the importance of lesion side, type of material, seizure history and deficits in other aspects of cognitive functions remain unanswered. In this study, patients who had undergone unilateral (15 right and 15 left) temporal lobectomy (TL) for the relief of epilepsy and 15 control subjects completed a range of public and autobiographical memory tests. Deficits in recall and recognition of details related to past famous world events were observed for both left and right TL groups. In addition, the left TL group showed impaired retrieval of famous names and TL patients as a group generated significantly fewer names of people from their own past. Current seizure- and medication-status influenced performance on a few measures, but duration of epilepsy and age of onset had no significant impact. Underlying cognitive deficits (especially naming ability) contributed to, but could not completely explain difficulties remembering the past. In particular, deficits in the ability to retrieve highly specific information learned in the past, such as names of famous people or details about famous events, remained evident in analyses that controlled for the impact of related cognitive skills.

One size does not fit all: Face emotion processing impairments in semantic dementia, behavioural-variant frontotemporal dementia and Alzheimer's disease are mediated by distinct cognitive deficits

Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimers disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17), SD (n = 12) or AD (n = 20) to an age- and education-matched group of healthy control subjects (n = 36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.

Tracking the progression of social cognition in neurodegenerative disorders

Background and purpose Behavioural-variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD) patients experience behavioural and emotion recognition alterations, yet understanding of how socioemotional processing is affected with disease progression is minimal. Additionally, evidence suggests that bvFTD patients with limited brain atrophy on neuroimaging at presentation (bvFTD-la) have a more benign course than those with marked atrophy (bvFTD-ma). Longitudinal investigation of these patients, however, is lacking. Methods We investigated general cognition, emotion recognition and sarcasm detection in 20 bvFTD (8 with limited brain atrophy) and 17 AD patients longitudinally and used mixed models analyses to determine the level and rates of decline across groups over time. Results At baseline, all patient groups performed worse than controls on general cognition and emotion recognition measures. The bvFTD-ma group showed significant impairment on the sarcasm detection task compared with controls. Longitudinally, an overall effect of time was present for general cognition (p<0.001); however, the rate of decline did not differ across groups. Trends for interactions between time and diagnosis were observed for both emotion recognition tasks (p=0.055; p=0.062), with the bvFTD-ma group declining more rapidly than AD or bvFTD-la groups. On the sarcasm detection task, the bvFTD-ma and AD patients declined, whereas bvFTD-la patients remained stable over time (p=0.002). Conclusions Tasks of sarcasm detection represent a clinically useful tool to differentiate between bvFTD and AD at baseline. Furthermore, tasks of socioemotional functioning can track progression within bvFTD and identify bvFTD patients more likely to show a faster rate of decline.

The functional role of the medio dorsal thalamic nucleus in olfaction

Olfaction is unique relative to other sensory modalities in terms of how its neuroanatomy is organized within the brain and its perceptual properties. Olfactory information processing occurs via connections made directly from primary processing areas (piriform cortex) to neocortical structures (orbitofrontal cortex) as well as indirectly via the medio-dorsal nucleus of the thalamus (MDNT). To date, little is known about the functional significance of the MDNT in olfactory information processing. The aim of this article is to review and discuss thalamic function in olfaction. We draw upon research in human neuroimaging, neuropsychology, as well as animal and neurophysiological studies on the thalamus and MDNT in general, before focusing our discussion on the effects of MDNT lesions specific to olfactory function. Finally, although these data are currently limited and sometimes conflicting, especially those based upon human pathology, the putative roles of the MDNT in olfactory information processing and notably its role in attention, are discussed.

PROSOPAMNESIA: A SELECTIVE IMPAIRMENT IN FACE LEARNING

The structures required for new learning, and those required for the representation of what has been learned, are believed to be distinct. This counterintuitive division of labour when considered alongside the localised nature of knowledge representation for at least some stimulus domains, implies that circumscribed new learning impairments should occasionally be found as a result of disconnection between learning mechanisms and domain-specific representations. We describe the most narrowly circumscribed new learning deficit so far reported, consisting of a selective new learning impairment for faces, which we term “prosopamnesia.” Logically, a diagnosis of prosopamnesia requires preserved face perception, preserved memory for material other than faces (including visual material), and preserved recognition of faces known premorbidly. We describe a patient who meets these criteria, thus supporting the division of labour between neural systems for learning and neural systems for knowledge representation, as well as providing further support for segregated face representation in cortex.

Right medial thalamic lesion causes isolated retrograde amnesia

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JGs profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Orbitofrontal cortex lesions result in abnormal social judgements to emotional faces

Facial expressions of emotion display a wealth of important social information that we use to guide our social judgements. The aim of the current study was to investigate whether patients with orbitofrontal cortex (OFC) lesions exhibit an impaired ability to judge the approachability of emotional faces. Furthermore, we also intended to establish whether impaired approachability judgements provided to emotional faces emerged in the presence of preserved explicit facial expression recognition. Using non-parametric statistics, we found that patients with OFC lesions had a particular difficulty using negative facial expressions to guide approachability judgements, compared to healthy controls and patients with frontal lesions sparing the OFC. Importantly, this deficit arose in the absence of an explicit facial expression recognition deficit. In our sample of healthy controls, we also demonstrated that the capacity to recognise facial expressions was not significantly correlated with approachability judgements given to emotional faces. These results demonstrate that the integrity of the OFC is critical for the appropriate assessment of approachability from negatively valenced faces and this ability is functionally dissociable from the capacity to explicitly recognise facial expressions.

Examining factors related to accelerated long-term forgetting in epilepsy using ambulatory EEG monitoring

Some patients with epilepsy demonstrate normal memory when this is tested at relatively short intervals (e.g., 30 min), but substantial loss over longer delay periods (e.g., days or weeks) when compared to healthy control subjects. This pattern of “accelerated long‐term forgetting” (ALF) affects the everyday lives of patients, yet goes undetected by standard neuropsychological memory tests, and its pathophysiologic basis is poorly understood. By testing memory over a period of concurrent ambulatory electroencephalography (EEG), the current study aimed to investigate possible factors contributing to ALF.