Judith L. Heidebrink

Temporoparietal Hypometabolism in Frontotemporal Lobar Degeneration and Associated Imaging Diagnostic Errors

OBJECTIVE To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD). DESIGN Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses. SETTING Academic medical centers. PATIENTS Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31). RESULTS Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD. CONCLUSIONS Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.

Is Dementia with Lewy Bodies the Second Most Common Cause of Dementia

Lewy bodies were originally described in isolated brainstem nuclei in persons with Parkinsons disease. They have since been recognized as a widespread and common neuropathologic finding in individuals with dementia. Dementia with Lewy bodies (DLB) is the preferred term for the dementia syndrome associated with Lewy bodies. Although DLB is acknowledged as the second most common degenerative dementia, trailing only Alzheimers disease, its ranking with respect to vascular dementia remains controversial. Large, community-based studies of DLB with postmortem confirmation are lacking. Available data suggest that DLB is more common than pure vascular dementia but not more common than any vascular contribution to dementia. (J Geriatr Psychiatry Neurol 2002; 15:000–000).

Reliability of Repeated Cognitive Assessment of Dementia Using a Brief Computerized Battery

Objective: The aim of this study was to evaluate the short-term stability and reliability of a brief computerized cognitive battery in established dementia types. Method: Patients were administered the computerized battery twice with administrations approximately 2 hours apart, with intervening conventional neuropsychological tests. Patients were classified clinically, via consensus conference, as healthy controls (n = 23), mild cognitive impairment (n = 20), Alzheimer’s disease (n = 52), dementia with Lewy Bodies ([DLB], n = 10), or frontotemporal dementia (n = 9). Results: Minimal practice effects were evident across Cog-State test administrations. Small magnitude improvements were seen across all groups on a working memory task, and healthy controls showed a mild practice effect on the accuracy of associative learning. Conclusions: In established dementia, administration of the CogState tasks appears sensitive to cognitive impairment in dementia. Repeat administration also provided acceptable stability and test-retest reliability with minimal practice effects at short test-retest intervals despite intervening cognitive challenges.

Validity of a Brief Computerized Cognitive Screening Test in Dementia

Background: While preliminary evidence supports the criterion validity of the CogState computerized brief battery in mild cognitive impairment (MCI) and Alzheimer disease (AD), definitive validation studies examining a wider range of dementia-related disorders relative to conventional neuropsychological techniques are necessary. Methods: Participants satisfying clinical consensus criteria for dementia (AD, n = 37; frontotemporal dementia, n = 7; and dementia with Lewy bodies, n = 5), MCI (n = 16), and the healthy controls (n = 22) were administered a battery of brief neuropsychological and select computerized (CogState) cognitive tests. The battery, administered through the University of Michigan Alzheimer’s Disease Research Center, included measures of processing speed, attention, working memory, and learning. Results: CogState and standard neuropsychological task scores were significantly lower for dementia participants than that of the nondementia groups (P < .05), with a single CogState test distinguishing control from MCI participants, but minimal differentiation existing between dementias using the CogState. Correlations were modest between conventional and computerized test scores, covering matching domains and mostly reflecting the multidimensional nature of cognitive paradigms. Conclusions: Results support the clinical validity of this brief computerized screening battery when used in established dementias, but not to differentiate between various dementias, and suggest that the select CogState battery’s effectiveness in identifying MCI from controls was not as strong as identifying specific dementias.

Vitamin E and memantine in Alzheimer's disease: Clinical trial methods and baseline data

Alzheimers disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha‐tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N‐methyl‐D‐aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD.

Neuropsychiatric Symptoms and Executive Functioning in Patients with Mild Cognitive Impairment: Relationship to Caregiver Burden

Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden. Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests. Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services. Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.

Validation of Consensus Panel Diagnosis in Dementia

BACKGROUND The clinical diagnosis of dementing diseases largely depends on the subjective interpretation of patient symptoms. Consensus panels are frequently used in research to determine diagnoses when definitive pathologic findings are unavailable. Nevertheless, research on group decision making indicates that many factors can adversely affect panel performance. OBJECTIVE To determine conditions that improve consensus panel diagnosis. DESIGN Comparison of neuropathologic diagnoses with individual and consensus panel diagnoses based on clinical scenarios only, fludeoxyglucose F 18 positron emission tomography images only, and scenarios plus images. SETTING Expert and trainee individual and consensus panel deliberations using a modified Delphi method in a pilot research study of the diagnostic utility of fludeoxyglucose F 18 positron emission tomography. PATIENTS Forty-five patients with pathologically confirmed Alzheimer disease or frontotemporal dementia. MAIN OUTCOME MEASURES Statistical measures of diagnostic accuracy, agreement, and confidence for individual raters and panelists before and after consensus deliberations. RESULTS The consensus protocol using trainees and experts surpassed the accuracy of individual expert diagnoses when clinical information elicited diverse judgments. In these situations, consensus was 3.5 times more likely to produce positive rather than negative changes in the accuracy and diagnostic certainty of individual panelists. A rule that forced group consensus was at least as accurate as majority and unanimity rules. CONCLUSIONS Using a modified Delphi protocol to arrive at a consensus diagnosis is a reasonable substitute for pathologic information. This protocol improves diagnostic accuracy and certainty when panelist judgments differ and is easily adapted to other research and clinical settings while avoiding the potential pitfalls of group decision making.

Psychiatric symptoms in preclinical behavioural-variant frontotemporal dementia in MAPT mutation carriers

Objective To characterise psychiatric symptoms in preclinical and early behavioural-variant frontotemporal dementia (bvFTD), a neurodegenerative disorder whose symptoms overlap with and are often mistaken for psychiatric illness. Methods The present study reports findings from a systematic, global, prospective evaluation of psychiatric symptoms in 12 preclinical carriers of pathogenic MAPT mutations, not yet meeting bvFTD diagnostic criteria, and 46 familial non-carrier controls. Current psychiatric symptoms, informant-reported symptoms and lifetime prevalence of psychiatric disorders were assessed with The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Neuropsychiatric Inventory Questionnaire. Fisher exact test was used to compare carriers and non-carriers’ lifetime prevalence of six DSM-IV disorders: major depressive disorder, panic attacks, alcohol abuse, generalised anxiety disorder, panic disorder, and depressive disorder not otherwise specified. Other DSM-IV disorders had insufficient prevalence across our sample for between-group comparisons, but are reported. Results Non-carriers had greater prevalence of mood and anxiety disorders than has been reported for a general reference population. Preclinical carriers had lower lifetime prevalence of mood and anxiety disorders than non-carriers, except for depressive disorder not otherwise specified, an atypical syndrome comprising clinically significant depressive symptoms which fail to meet criteria for major depressive disorder. Conclusion Findings suggest that early psychiatric symptoms of emergent bvFTD may manifest as emotional blunting or mood changes not cleanly conforming to criteria for a DSM-defined mood disorder.

Diagnostic Profiles of Patients Differentially Failing Executive Functioning Measures.

Objective: Limited research exists to explain differential executive functioning impairment in clinical populations, particularly between the Wisconsin Card Sorting Task (WCST) and the Trail Making Test (TMT). Methods: The distribution of clinical diagnoses was examined in patients failing none, one, or both tasks, and executive task performance was compared among dementia-related diagnoses. Two hundred and sixty-six participants received evaluations through an Alzheimer’s Disease Research Center, which included executive tasks. Dementia-related diagnoses were established through consensus. Results: Chi-square analyses indicated that TMT failure, with or without WCST failure, possessed higher associations with dementia diagnoses. Repeated measures analysis of variance similarly indicated that participants with dementia, especially mild and moderate severity, performed worse on TMT. Conclusions: Executive dysfunction was observed in dementia-related diagnoses, and TMT failure was implicated in dementia in higher proportions than WCST impairment. Trail Making Test appears more sensitive than WCST for assessing executive impairment across diagnoses, especially when time and resources are limited in screening and clinical settings.

The prevalence and impact of type 2 diabetes in mild cognitive impairment and Alzheimer's disease

Background: There has been interest in an unusual clinical phenomenon, in which a patient draws a complex figure in a position that is grossly rotated relative to the original. This implicates theories of objective recognition and visuospatial function. It has been claimed that rotated drawings was related to the dysfunction of parieto-occipital lobe or frontal lesions. However, the range of perfomance as well as anatomical correlation remains obscure. Methods: 76 year old woman with right caudate nucleus infarction case. Results: A 76-year-old, uneducated woman visited to our hospital because she had wandering on the familiar road to the daughter’s house 2 days ago. She had no history of impairment with cognition and active daily living (ADL). She had recognized hypertension for twenty years. On neurological examination, she was alert and no deficit of motor and sensory system on grossly except cognition found. Her performance on neuropsychological tests was impaired in frontal executive function and verbal memory as well as copying of Rey-Osterrieth Complex figure. The figure was rotated in copying tasks by 90-degree conterclockwise. On Brain Magnetic Resonance Image (MRI), acute infarction in the head of right caudate nucleus region was observed. After 2 month later, rotation recorvered at follow up neuropsychological evaluation. Conclusions: Many connections exist between frontal lobe and basal ganglia. Our result suggests that frontal lobebasal ganglia dysfunction by caudate infarction can be concerned for rotated drawing.