Lisa Cipolotti

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease.

Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimers disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimers disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimers disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left‐sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimers disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimers disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role. Ann Neurol 2001;49:433–442

Long-term retrograde amnesia… the crucial role of the hippocampus

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Toward a multiroute model of number processing: Impaired number transcoding with preserved calculation skills

This article describes a patient (S.A.M.), suffering from a progressive neurological degenerative condition of unknown origin, who showed a severe difficulty in number transcoding tasks. S.A.M. could recognize and understand arabic numerals and written number names, but he could neither read them aloud nor write them. However, he had a well maintained ability to perform oral and written calculations. The striking pattern of performance observed in S.A.M. suggests that deficits affecting the ability to produce arabic or verbal numerals can be specific to particular task demands. This observation cannot be easily accommodated by current models of numerical processing. A new multiroute model for numerical processing is proposed to account for S.A.M.s pattern of performance. This model adds asemantic transcoding pathways to the semantic processing mechanisms proposed by the M. McCloskey model.

Semantic memory and reading abilities: a case report.

We document the unexpected dissociation of preserved reading skills in a patient with severely impaired semantic memory. The common co-occurrence between impairment of word meaning and surface dyslexia has not been observed. The patient (hereafter called DRN) had marked naming and word comprehension difficulties. A strong word frequency effect was observed on tests of word comprehension but was absent in a test of word reading. DRNs ability to read both regular and exception words that he failed to comprehend was remarkably well preserved. We will argue that these findings provide further support for the independence of semantic and phonological processing. ( JINS , 1995, I , 104–110.)

The differing roles of the frontal cortex in fluency tests

Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n=47) and posterior (n=20) lesions. Patients and controls (n=35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left-phonemic and right-design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.

Fractionation of visual memory: agency detection and its impairment in autism

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. In addition, there have been hints from studies with individuals with autism that these cognitive subsystems can fractionate developmentally. However, there has been a paucity of systematic investigations. The present study involves the analysis of visual memory of a population of individuals with autism and age- and VIQ-matched comparison individuals. The individuals with autism presented selective impairments in face recognition in comparison to both the age- and VIQ-matched comparison populations. In addition, they were impaired relative to the age-matched comparison group on recognition memory for potential agents (i.e. objects capable of self-propelled motion) whether they were living (cats and horses) or non-living (motorbikes). In contrast, they were selectively superior relative to the VIQ-matched comparison group on recognition memory for such objects as topographical stimuli (buildings) and leaves that clearly do not have agency. The data is interpreted in terms of reduced sensitivity to agency cues in individuals with autism and general information processing capacity.

Taking both sides: do unilateral anterior temporal lobe lesions disrupt semantic memory?

The most selective disorder of central conceptual knowledge arises in semantic dementia, a degenerative condition associated with bilateral atrophy of the inferior and polar regions of the temporal lobes. Likewise, semantic impairment in both herpes simplex virus encephalitis and Alzheimers disease is typically associated with bilateral, anterior temporal pathology. These findings suggest that conceptual representations are supported via an interconnected, bilateral, anterior temporal network and that it may take damage to both sides to produce an unequivocal deficit of central semantic memory. We tested and supported this hypothesis by investigating a case series of 20 patients with unilateral temporal damage (following vascular accident or resection for tumour or epilepsy), utilizing a test battery that is sensitive to semantic impairment in semantic dementia. Only 1/20 of the cases, with a unilateral left lesion, exhibited even a mild impairment on the receptive semantic measures. On the expressive semantic tests of naming and fluency, average performance was worse in the left- than right-unilateral cases, but even in this domain, only one left-lesion case had scores consistently more than two standard deviations below control means. These results fit with recent parallel explorations of semantic function using repetitive transcranial magnetic stimulation as well as functional imaging in stroke aphasic and neurologically intact participants. The evidence suggests that both left and right anterior temporal lobe regions contribute to the representation of semantic memory and together may form a relatively damage-resistant, robust system for this critical aspect of higher cognition.

Recollection and familiarity in dense hippocampal amnesia: a case study

In the amnesia literature, disagreement exists over whether anterograde amnesia involves recollective-based recognition processes and/or familiarity-based ones depending on whether the anatomical damage is restricted to the hippocampus or also involves adjacent areas, particularly the entorhinal and perirhinal cortices. So far, few patients with well documented anatomical lesions and detailed assessment of recollective and recognition performance have been described. We report a comprehensive neuroanatomical assessment and detailed investigation of the anterograde memory functions of a previously described severe amnesic patient (VC). The results of four previously published neuroradiological investigations (resting PET, qualitative MRIs, volumetric MRI and functional MRI) together with the results of two new investigations (voxel-based morphometry and magnetic resonance spectroscopy) are presented. The consistent finding across these different qualitative and quantitative examinations of VCs brain has shown that there is primarily structural and functional abnormality located selectively in the hippocampus bilaterally. Marked impairments in both verbal and non-verbal recall and recognition standardized memory tests were documented in the context of VCs intact cognitive profile and normal semantic memory. The results of five new experimental recognition memory tests tapping recollection and familiarity using verbal, topographical (buildings and landscapes) and unknown human faces memoranda revealed striking differential effects according to the type of stimuli used. A receiver operating characteristic analysis revealed that VCs recollective- and familiarity-based recognition processes were well preserved for unknown human faces. In contrast, recollective-based recognition for verbal and topographical material was at floor. Familiarity-based recognition was also impaired, significantly below controls for verbal and buildings memoranda and quite weak, although not reaching significance, for landscapes. These data suggest that the hippocampus is involved in recollective processes of verbal and topographical stimuli. It also plays an appreciable role in familiarity processes for these stimuli. However, recollection and familiarity of human faces appear not to depend on this region.

Autobiographical memory loss and confabulation in Korsakoff's syndrome: a case report.

A patient with Korsakoffs syndrome is presented, who showed a selective loss of Autobiographical Memory along with a preserved Semantic Memory. Confabulations were a prominent feature. They only involved Autobiographical Memory and were persistent in time and consistent in content. The implications of these findings for understanding the nature of Autobiographical Memory impairment are discussed.

MRS shows abnormalities before symptoms in familial Alzheimer disease

Background: Pathologic change in Alzheimer disease (AD) begins some years before symptoms. MRS has the potential to detect metabolic abnormalities reflecting this early pathologic change. Presenilin 1 (PS1) and amyloid precursor protein (APP) mutation carriers have a nearly 100% risk of developing AD and may be studied prior to symptom onset. Methods: Short echo time proton MR spectra were acquired from a midline posterior cingulate voxel in presymptomatic carriers of PS1 or APP mutations (“presymptomatic mutation carriers” [PMCs]; n = 7) and age- and sex-matched control subjects (n = 6). Ratios of N-acetyl aspartate (NAA), myo-inositol (MI), and choline-containing compounds (Cho) to creatine (Cr) were measured and NAA/MI calculated. Regression analyses and t tests were performed after log transformation. Results: PMC and control subjects were matched for age and sex. PMC subjects were 1.7 to 21.6 years (mean 9.8 years) before expected symptom onset, predicted from family-specific mean age at onset. Age did not significantly affect metabolite ratios. Geometric mean ratios in control subjects were as follows: NAA/Cr = 1.75, MI/Cr = 0.59, and NAA/MI = 2.95. NAA/Cr and NAA/MI were significantly reduced in PMC relative to controls (NAA/Cr mean decrease 10% [95% CI 2 to 18%]; NAA/MI mean decrease 25% [95% CI 3 to 44%]). MI/Cr was increased in PMC, but the differences did not achieve significance (19% increase [95% CI 1% decrease to 41% increase]; p = 0.07)). In PMCs, reduction in NAA/MI (p = 0.001) and MI/Cr (p = 0.002) were related to proximity of expected age at onset. Conclusions: Metabolic changes are detectable in presymptomatic mutation carriers years before expected onset of Alzheimer disease. Their magnitude is related to proximity of expected age at onset.