Functional Specialization of the Medial Temporal Lobes in Human Recognition Memory: Dissociating Effects of Hippocampal versus Parahippocampal Damage.

A central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes in recognition memory. Using two recognition memory paradigms, we tested a rare patient (MH) with a perirhinal lesion that appeared to spare the hippocampus. Consistent with a similar previous case, MH showed impaired familiarity and preserved recollection. When compared with patients with hippocampal lesions appearing to spare perirhinal cortex, MH showed greater impairment on familiarity and less on recollection. Nevertheless, the hippocampal patients also showed impaired familiarity compared with healthy controls. However, when replacing this traditional categorization of patients with analyses relating memory performance to continuous measures of damage across patients, hippocampal volume uniquely predicted recollection, whereas parahippocampal, rather than perirhinal, volume uniquely predicted familiarity. We consider whether the familiarity impairment in MH and our patients with hippocampal lesions arises from "subthreshold" damage to parahippocampal cortex (PHC). Our data provide the most compelling neuropsychological support yet for dual-process models of recognition memory, whereby recollection and familiarity depend on different MTL structures, and may support a role for PHC in familiarity. Our study highlights the value of supplementing single-case studies with examinations of continuous brain-behavior relationships across larger patient groups.

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis.

OBJECTIVE: Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. METHOD: A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. RESULTS: Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). CONCLUSION: VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.

11 C-PE2I and 18 F-Dopa PET for assessing progression rate in Parkinson's: A longitudinal study.

BACKGROUND: 18 F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18 F-dopa with the highly selective dopamine transporter radioligand 11 C-PE2I for the assessment of motor severity and rate of progression in PD. METHODS: Thirty-three mild-moderate PD patients underwent 18 F-dopa and 11 C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months. RESULTS: Standard multiple regression at baseline indicated that 11 C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18 F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11 C-PE2I BPND and motor severity across the whole striatum bilaterally. 18 F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal Δ11 C-PE2I BPND , ΔUPDRS-III, and Δbradykinesia-rigidity, whereas no significant associations were found for Δ18 F-dopa Ki . One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between Δ11 C-PE2I BPND and Δbradykinesia-rigidity. CONCLUSIONS: Striatal 11 C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18 F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11 C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 International Parkinson and Movement Disorder Society.

Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients.

BACKGROUND: The objective of this study was to investigate in vivo the ability of levodopa/carbidopa intestinal gel infusions to produce sustained striatal dopamine levels and to improve clinical outcomes in Parkinson's disease patients. METHODS: Six advanced Parkinson's disease patients had serial [11 C]raclopride PET to assess levodopa/carbidopa intestinal gel infusion-induced rises in striatal dopamine as reflected by a fall in dopamine-D2/3 receptor availability. Parkinson's disease patients had baseline scan OFF-dopaminergic stimulation and 2 scans following initiation of levodopa/carbidopa intestinal gel infusions. Striatal D2/3 binding was measured in striatal subregions corresponding to sensorimotor, limbic, and cognitive/associative function. RESULTS: Mean striatal [11 C]raclopride nondisplaceable binding potential decreased by 14.0% to 16.7% in sensorimotor, 12.0%-14.4% in limbic, and 8.7%-11.6% in cognitive/associative function subregions at 1- to 10-hour points (P < 0.01). Sensorimotor subregion [11 C]raclopride nondisplaceable binding potential reductions correlated with reductions in Unified Parkinson's Disease Rating Scale Part III scores over the course of the infusion (r = 0.81; P < 0.05). CONCLUSIONS: Levodopa/carbidopa intestinal gel infusions generate a stable rise in striatal dopamine levels and are associated with improvements in motor manifestations. © 2016 International Parkinson and Movement Disorder Society.

Aberrant nigral diffusion in Parkinson's disease: A longitudinal diffusion tensor imaging study.

BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored. METHODS: We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach. RESULTS: Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time. CONCLUSION: Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.

Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson's disease.

Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson's disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson's disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson's disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues. We hypothesized that exposure to visual sexual cues would trigger increased sexual desire in patients with Parkinson's disease with hypersexuality that would correspond to changes in brain activity in regions linked to dopaminergically stimulated sexual motivation. Patients with Parkinson's disease with hypersexuality were scanned ON and OFF dopamine drugs, and their results were compared with a group of 12 Parkinson's disease control patients without hypersexuality or other impulse control disorders. Exposure to sexual cues significantly increased sexual desire and hedonic responses in the Parkinson's disease hypersexuality group compared with the Parkinson's disease control patients. These behavioural changes corresponded to significant blood oxygen level-dependent signal changes in regions within limbic, paralimbic, temporal, occipital, somatosensory and prefrontal cortices that correspond to emotional, cognitive, autonomic, visual and motivational processes. The functional imaging data showed that the hypersexuality patients' increased sexual desire correlated with enhanced activations in the ventral striatum, and cingulate and orbitofrontal cortices. When the patients with Parkinson's disease with hypersexuality were OFF medication, the functional imaging data showed decreases in activation during the presentation of sexual cues relative to rest. These deactivations were not observed when the patients were ON medication, suggesting that dopamine drugs may release inhibition within local neuronal circuits in the cerebral cortex that may contribute to compulsive sexual behaviour. The findings of this study have implications with respect to the potential influence of cue exposure via exposure to mass media in enhancing libido, which in this group of vulnerable patients can lead to devastating social consequences and occasionally, custodial sentences. Stimulation through exposure to sexual visual cues in patients with Parkinson's disease with hypersexuality provides a motivational impetus for seeking this reward behaviour through activations and deactivations of cerebral cortex.

Ambient particulate matter and its potential neurological consequences.

Exposure to ambient air pollution has been consistently associated with respiratory and cardiovascular disease. However, the neurological effects of air pollution have received little attention. It is suggested that the components of air pollution, such as particulate matter (PM) and specifically ultrafine particulate matter (UFP), may have the potential to extend beyond pulmonary organs to the central nervous system (CNS) and, ultimately, the brain. The transport mechanisms are not clear, although at least four possible routes have been proposed implicating PM and UFP in neurological disease processes. A limited number of studies have been undertaken to assess the role of PM and UFP in CNS diseases, including migraine, headache, stroke, Alzheimer's disease, and Parkinson's disease. Considering the high prevalence of such CNS diseases, along with the frequent and increasing exposure to ambient air pollution, it is important to highlight possible associations with regards to preventative, monitoring, and control measures. This article aimed to review the literature in relation to translocation routes of PM and UFP and their potential role in neurological disease processes.

Reduplicative paramnesia: a review.

BACKGROUND: Reduplicative paramnesia (RP) is a content-specific delusional misidentification syndrome (DMS) which has received little attention in the research literature relative to other DMS. RP is thought to result from an organic rather than psychiatric cause distinguishing it from other DMS. Our systematic review examines the research literature investigating the prevalence, symptomatology and potential neurologic mechanisms underlying RP. SAMPLING AND METHODS: MEDLINE, PsycINFO, and the Cochrane Library were searched (from 1966 to February 10, 2012) with the reference lists of relevant articles examined. Case reports, clinical studies and post-mortem studies focusing on, or referring to, RP were included. RESULTS: There is a paucity of literature regarding the potential mechanisms underlying the psychological, cognitive and neurological aspects of RP. The available literature is limited by the lack of systematic clinical studies and in vivo investigations with current findings remaining only speculative. However, there does appear to be a consensus that RP may have a neurologic rather than psychiatric cause and that right and bifrontal lesions as well as the cognitive dissonance associated with memory, visuospatial and impaired conceptual integration are common factors in RP presentation. CONCLUSIONS: This area requires further extensive systematic research with supplementary in vivo data. Current studies suggest that focal lesions within the frontal lobe may account for the onset of RP.

Serotonergic mediated body mass index changes in Parkinson's disease.

More than 50% of patients with Parkinson's disease (PD) are expected to show abnormalities with their weight in a process that starts several years before the diagnosis. The serotonergic (5-HT) system has been proposed to regulate appetite and the 5-HT transporter (SERT) is a key modulator of 5-HT metabolism. Here, we hypothesized that a dysfunctional 5-HT system could be responsible for alterations of weight in PD and we sought to investigate this in vivo. Thirty four PD patients had Body Mass Index (BMI) changes monitored over a 12-month period and one positron emission tomography (PET) brain scan with (11)C-DASB, a selective marker of SERT availability, during their second clinical assessment. Results were compared with those of a group of 10 normal controls. Half (17) of the PD patients showed abnormal BMI changes over the 12-month period; 12 lost while 5 gained weight. PD patients with abnormal BMI changes showed significantly raised (11)C-DASB binding in rostral raphe nuclei, hypothalamus, caudate nucleus and ventral striatum compared to cases with no significant BMI changes. (11)C-DASB binding in other regions was similarly decreased in the PD BMI subgroups compared to normal controls. BMI gainers showed significantly raised (11)C-DASB binding in anterior cingulate cortex (ACC) compared to BMI losers. Our findings suggest that abnormal BMI changes over a 12-month period are linked with relatively raised SERT availability in PD on an overall background of decreased 5-HT function. The regions implicated are the rostral raphe nuclei and its connections to limbic and cognitive areas. It is conceivable that 5-HT agents could help alleviate abnormal changes in BMI in PD.

Sleep disturbance and impulsive-compulsive behaviours in Parkinson's disease.

OBJECTIVES: Impulsive-compulsive behaviours (ICBs) in Parkinson's disease (PD) have been anecdotally linked with impaired sleep. The authors investigate measures of sleep in PD patients with and without ICBs, and in healthy controls. METHODS: The authors compare Parkinsonian features, measures of depression, anxiety and mania, and sleep disturbance in 30 PD patients with ICBs (PD+ICB), 62 PD patients without ICBs (PD-ICB) and 48 healthy controls. RESULTS: PD+ICB patients had a younger age of PD onset, took more dopamine replacement therapy (DRT) and had worse sleep, and elevated anxiety, depression and mania scores. Using multiple linear regression analyses, the total anxiety and depression scores, and presence of ICBs were the only variables associated with poorer sleep in PD. CONCLUSIONS: PD+ICB patients may show enhanced psychomotor effects of DRT that may in turn contribute to poor sleep quality. Sleep disturbance should be specifically queried in PD+ICB patients.

Serotonergic dysfunction in Parkinson's disease and its relevance to disability.

Growing evidence suggests that Parkinson's disease is not solely affecting the dopaminergic system. Results from biochemical, animal, postmortem, and functional imaging studies have revealed that other neurotransmitter systems are affected as well, including the serotonergic system. With the use of in vivo positron emission tomography functional imaging, it has been shown that serotonergic terminals are affected at a varying, nonlinear degree starting early in the clinical course of Parkinson's disease. Tremor and the majority of nonmotor symptoms do not seem to respond adequately to dopaminergic medication. Recent studies suggest that serotonergic dysfunction has a direct relevance to Parkinson's disease symptoms, the so-called nonmotor symptoms, including depression, fatigue, weight changes, and visual hallucinations. These in vivo findings indicate that agents acting on the serotonergic system could help towards alleviating these symptoms. This paper aims to review the current literature and to highlight the need for further in vivo investigations.

Longitudinal changes in movement-related functional MRI activity in Parkinson's disease patients.

INTRODUCTION: Functional brain imaging has shown alterations in the basal ganglia, cortex and cerebellum in Parkinson's disease patients. However, few functional imaging studies have tested how these changes evolve over time. Our study aimed to test the longitudinal progression of movement-related functional activity in Parkinson's disease patients. METHODS: At baseline, 48 Parkinson's disease patients and 16 healthy controls underwent structural and functional magnetic resonance imaging during a joystick motor task. Patients had repeated imaging after 18-months (n = 42) and 36-months (n = 32). T-tests compared functional responses between Parkinson's disease patients and controls, and linear mixed effects models examined longitudinal differences within Parkinson's disease. Correlations of motor-activity with bradykinesia, rigidity and tremor were undertaken. All contrasts used whole-brain analyses, thresholded at Z > 3.1 with a cluster-wise P < 0.05. RESULTS: Baseline activation was significantly greater in patients than controls across contralateral parietal and occipital regions, ipsilateral precentral gyrus and thalamus. Longitudinally, patients showed significant increases in cerebellar activity at successive visits following baseline. Task-related activity also increased in the contralateral motor, parietal and temporal areas at 36 months compared to baseline, however this was reduced when controlling for motor task performance. CONCLUSION: We have shown that there are changes over time in the blood-activation level dependent response of patients with Parkinson's disease undertaking a simple motor task. These changes are observed primarily in the ipsilateral cerebellum and may be compensatory in nature.

Staging of serotonergic dysfunction in Parkinson's disease: an in vivo 11C-DASB PET study.

Thirty Parkinson's disease (PD) patients were divided into three equal groups according to their disease duration while 10 normal healthy volunteers matched for age and sex served as a control group. Striatal and extrastriatal serotonergic function was studied with (11)C-DASB PET, a marker of serotonin transporter availability. (11)C-DASB binding was correlated with disease disability and exposure to dopaminergic therapy. We found significant (11)C-DASB binding reductions in striatal, brainstem, and cortical regions in PD but no correlations were evident between (11)C-DASB binding and UPDRS scores, Hoehn &Yahr staging, disease duration and level of exposure to dopaminergic therapy. Our results suggest that progressive non-linear serotonergic dysfunction occurs in PD but it does not determine levels of disability. Additionally, chronic exposure to dopaminergic therapy does not appear to influence SERT binding.

Excessive hoarding in Parkinson's disease.

Hoarding is seen in several psychiatric conditions, but has not been specifically assessed in Parkinson's disease (PD). This study investigates hoarding tendency amongst patients with PD, and its association with impulsive-compulsive spectrum behaviors (ICBs). We compare clinical features, measures of hoarding, impulse buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in 39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD - ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders. Compulsive shoppers scored higher than other varieties of ICB on excessive acquisition measures. Hoarding correlated positively with impulsive buying, obsessive-compulsive symptoms, PD duration, and negatively with self-control measures. Using multivariate regression analyzes, the presence of ICBs and measures of impulsive buying were the only variables independently associated with hoarding in PD. The association of hoarding with other ICBs and low trait impulse control suggests that excessive hoarding is related to the spectrum of impulsive behaviors in PD.

Pathologic tearfulness after limbic encephalitis: A novel disorder and its neural basis.

OBJECTIVE: We investigated the nature and neural foundations of pathologic tearfulness in a uniquely large cohort of patients who had presented with autoimmune limbic encephalitis (aLE). METHODS: We recruited 38 patients (26 men, 12 women; median age 63.06 years; interquartile range [IQR] 16.06 years) in the postacute phase of aLE who completed questionnaires probing emotion regulation. All patients underwent structural/functional MRI postacutely, along with 67 age- and sex-matched healthy controls (40 men, 27 women; median age 64.70 years; IQR 19.87 years). We investigated correlations of questionnaire scores with demographic, clinical, neuropsychological, and brain imaging data across patients. We also compared patients diagnosed with pathologic tearfulness and those without, along with healthy controls, on gray matter volume, resting-state functional connectivity, and activity. RESULTS: Pathologic tearfulness was reported by 50% of the patients, while no patient reported pathologic laughing. It was not associated with depression, impulsiveness, memory impairment, executive dysfunction in the postacute phase, or amygdalar abnormalities in the acute phase. It correlated with changes in specific emotional brain networks: volume reduction in the right anterior hippocampus, left fusiform gyrus, and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and right middle frontal gyrus, and abnormal hemodynamic activity in the left fusiform gyrus, right inferior parietal lobule, and ventral pons. CONCLUSIONS: Pathologic tearfulness is common following aLE, is not a manifestation of other neuropsychiatric features, and reflects abnormalities in networks of emotion regulation beyond the acute hippocampal focus. The condition, which may also be present in other neurologic disorders, provides novel insights into the neural basis of affective control and its dysfunction in disease.

Network-wide abnormalities explain memory variability in hippocampal amnesia.

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n = 38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience.

In vivo visualization of age-related differences in the locus coeruleus.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience-an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span.

Lateral parietal contributions to memory impairment in posterior cortical atrophy.

Objective: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures. Methods: Eighteen PCA patients, 15 typical Alzheimer's disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance. Results: Compared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe. Conclusions: The findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA.

Association between precuneus volume and autobiographical memory impairment in posterior cortical atrophy: Beyond the visual syndrome.

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimer's disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimer's disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimer's disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy.