Neurobiology of delusions, memory, and insight in Alzheimer disease.

OBJECTIVE: Delusional thoughts are common among patients with Alzheimer disease (AD) and may be conceptually linked to memory deficits (cannot recall accurate information, which leads to inaccurate beliefs) and poor insight (unable to appreciate the illogic of beliefs). This study's goals were to examine the clinical associations among delusions, memory deficits, and poor insight; explore neurobiologic correlates for these symptoms; and identify shared mechanisms. METHODS: In a cross-sectional analysis, 88 outpatients with AD (mean Mini-Mental State Exam score: 19.3) were studied. Delusional thoughts were assessed with the Neuropsychiatric Inventory, level of inaccurate insight was assessed with the Neurobehavioral Rating Scale, and memory was assessed with the Mattis Dementia Rating Scale memory subscale. (18)F-fluorodeoxyglucose positron emission tomography was used to measure regional cortical metabolism. Relationships between clinical ratings and regional cortical metabolic activity (voxel-based) were assessed using SPM2. RESULTS: Patients with delusions had lower Dementia Rating Scale memory subscale scores. Neurobehavioral Rating Scale inaccurate insight scores were no different in those with and without delusions. Cortical metabolic activity was lower in the right lateral frontal cortex, orbitofrontal cortex, and bilateral temporal cortex in patients with delusions. Low cortical metabolic activity in the right lateral, inferior, and medial temporal cortex was associated with poorer memory. This region partially overlapped the region of hypometabolism associated with delusions. In contrast, low cortical metabolic activity in bilateral medial frontal cortex was associated with poor insight. CONCLUSION: Delusions in AD are associated with dysfunction in specific frontal and temporal cortical regions. Delusions are partially clinically and neurobiologically linked to memory deficits but not to poor insight.

Attentional networks reveal executive function deficits in posttraumatic stress disorder.

Executive function was assessed with the Trail Making Test (Army Individual Test Battery; M. D. Lezak, 1983), the Comprehensive Trail Making Test (C. Reynolds, 2002), and a neurocognitive measure of executive control (Attentional Network Task [ANT]; J. I. Fan, B. D. McCandliss, T. Somer, A. Raz, & M. I. Posner, 2002) in 19 undergraduates with posttraumatic stress disorder (PTSD; Posttraumatic Stress Disorder Symptom Scale-Self-Report version; E. B. Foa, D. S. Riggs, C. V. Dancu, & B. O. Rothbaum, 1993), 15 high trauma participants without PTSD, and 18 low trauma control participants. Although groups did not differ on any trail making task or on the ANT measures of alerting or orienting, PTSD participants were significantly more impaired on the ANT executive network index than were high or low trauma control participants, even when level of depressive symptoms was covaried. Previous animal research identified a relationship between dopamine and the ANT measure of executive function. Elevated PTSD symptom severity and levels of hyperarousal, reexperiencing, and avoidance-numbing were associated significantly with executive function deficits indexed by the ANT. These results indicate a potentially subtle but specific deficit in executive function and a possible relationship between PTSD symptoms and irregularities in dopamine function.

The functional neuroanatomy of verbal memory in Alzheimer's disease: [18F]-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) correlates of recency and recognition memory.

INTRODUCTION: The objective of this study was to distinguish the functional neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning task. METHOD: In 81 Veterans diagnosed with dementia due to AD, we conducted a cluster-based correlation analysis to assess the relationships between recency and recognition memory scores from the CERAD Word Learning Task and cortical metabolic activity measured using [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). RESULTS: AD patients (Mini-Mental State Examination, MMSE mean = 20.2) performed significantly better on the recall of recency items during learning trials than of primacy and middle items. Recency memory was associated with cerebral metabolism in the left middle and inferior temporal gyri and left fusiform gyrus (p < .05 at the corrected cluster level). In contrast, recognition memory was correlated with metabolic activity in two clusters: (a) a large cluster that included the left hippocampus, parahippocampal gyrus, entorhinal cortex, anterior temporal lobe, and inferior and middle temporal gyri; (b) the bilateral orbitofrontal cortices (OFC). CONCLUSIONS: The present study further informs our understanding of the disparate functional neuroanatomy of recency memory and recognition memory in AD. We anticipated that the recency effect would be relatively preserved and associated with temporoparietal brain regions implicated in short-term verbal memory, while recognition memory would be associated with the medial temporal lobe and possibly the OFC. Consistent with our a priori hypotheses, list learning in our AD sample was characterized by a reduced primacy effect and a relatively spared recency effect; however, recency memory was associated with cerebral metabolism in inferior and lateral temporal regions associated with the semantic memory network, rather than regions associated with short-term verbal memory. The correlates of recognition memory included the medial temporal lobe and OFC, replicating prior studies.