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Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. Objective: To evaluate the potential roles of positron emission tomography with fluodeoxyglucose F 18 (18 FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. Design, Setting, and Patients: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an 18 FDG-PET study. Forty-eight subjects were followed up periodically for at least 1 year, and progression to dementia was evaluated. Main Outcome Measures: Brain glucose metabolism and memory scores. Results: Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable" aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test-Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical 18 FDG-PET AD pattern, and scores of 7 or higher were associated with hypometabolism in the dorsolateral frontal cortex and no progression to AD. Conclusion: These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that 18 FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD.

In patients with the frontal variant of frontotemporal lobar degeneration (fv-FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathetic form) to disinhibition with agitation (disinhibited form). These clinical presentations may be related to specific regional cerebral dysfunction and to deficit in the serotoninergic system. We studied cerebral glucose uptake using (18)F-fluorodeoxyglucose and positron emission tomography in 18 patients fulfilling clinical criteria for fv-FTLD and showing, respectively, an apathetic or disinhibited behavioral syndrome. In eight of these patients, we also evaluated the 5-hydroxytryptamine-2A receptor cerebral receptor distribution with [(11)C]MDL and positron emission tomography. We found a reduction of frontal glucose metabolism in the whole group of fv-FTLD patients. Apathetic syndrome was associated with a prevalent dorsolateral and frontal medial hypometabolism, whereas the disinhibited syndrome demonstrated a selective hypometabolism in interconnected limbic structures (the cingulate cortex, hippocampus/amygdala, and accumbens nucleus). The in vivo measurements of [(11)C]MDL indicated a significant reduction of 5-hydroxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate cortices. These (18)F-fluorodeoxyglucose positron emission tomography changes can be considered as specific functional markers of the different behavioral presentations in fv-FTLD. The serotoninergic system dysfunction provides a rationale for therapeutic trials with selective serotonin reuptake inhibitors.

Background: An early differentiation of Alzheimer’s disease (AD) from frontotemporal dementia (FTD) is important, since these conditions are essentially different regarding prognosis and therapeutical approach. Until now, no single test is available which allows a reliable differentiation. The Frontal Assessment Battery (FAB) has been found to have good reliability in identifying an executive deficit in frontal syndromes and in extrapyramidal disorders. The ability of the FAB to distinguish AD from FTD in mildly demented patients is less clearly assessed. Methods: We compared FAB scores in a consecutive series of 33 FTD (frontal variant) and 85 AD patients. Results: FAB global scores in the two groups were very similar, also when considering only mildly demented subgroups [Mini Mental State Examination (MMSE) score ≧20; 20 FTD and 38 AD patients]. Considering FAB subscores, only the ‘go-no go’ subtest showed a significant difference, reflecting a poorer inhibitory motor control in AD patients. FAB scores in the two groups of patients correlated with global cognitive decline (MMSE), and with executive and visuospatial test scores, showing good concurrent validity. Conclusion: The FAB does not differentiate patients with AD from those with FTD, like all other executive tests. However, it may be useful in the examination of executive function in AD, FTD and several other pathological conditions.

The “frontal aging hypothesis” predicts that brain senescence affects predominantly the prefrontal regions. Preliminary evidence has recently been gathered in favour of an age-related change in a typically frontal process, i.e. decision making, using the Iowa Gambling Task (IGT), but overall findings have been conflicting. Following the traditional scoring method, coupled with a qualitative analysis, in the present study we compared IGT performance of 40 young (mean age: 27.9 ± 4.7) and 40 old (mean age: 65.4 ± 8.6) healthy adults and of 18 patients affected by frontal lobe dementia of mild severity (mean age: 65.1 ± 7.4, mean MMSE score: 24.1 ± 3.9). Quantitative findings support the notion that decision making ability declines with age; moreover, it approximates the impairment observed in executive dysfunction due to neurodegeneration. Results of the qualitative analysis did not reach statistical significance for the motivational and learning decision making components considered, but approached significance for the attentional component for elderly versus young normals, suggesting a possible decrease in the ability to maintain sustained attention during complex and prolonged tasks as the putative deficit underlying impaired decision making in normal aging.

Background: Executive dysfunction in Alzheimer’s disease (AD) has been recently recognized as an early and prominent clinical sign. The Tower of London (ToL), a task specifically devised to test executive functions of visuospatial planning and problem solving, has frequently been used in neuropsychological experiments, but rarely in the clinical ground. Methods: One hundred and sixty-one AD patients and 212 nondemented healthy controls were administered a simplified ToL version. Results: AD patients were significantly impaired (p < 0.0001) in all ToL scores and in the total execution time. The ‘accuracy’ score of ToL at a cut off of ≤29/36 yielded a sensitivity of 71.2% and a specificity of 76.4% (AUC 0.79) for the diagnosis of AD versus controls. Conclusions: Visuospatial planning and problem solving are significantly impaired in early dementia of the Alzheimer’s type. A successful sensitivity/specificity ratio, the independence of education and the simplicity of this version of ToL make it a useful executive functioning screening test for early AD.

Verbal confabulation (VC) has been described in several pathological conditions characterized by amnesia and has been defined as ‘statements that involve distortion of memories’. Here we describe another kind of confabulation (graphic confabulation, GC), evident at the recall of the Rey-Osterrieth complex figure (ROCF). In a retrospective study of 267 patients with mild-to-moderate dementia, 14 patients (4.9 %) recalled the abstract ROCF as drawings with recognizable semantic meaning. VC was evident at the story recall test in 19.8% of the study participants. VC and GC were homogeneously distributed among the different types of dementia. VC has been proposed to originate from complex interactions of amnesia, motivational deficit and dysfunction of monitoring systems. On the contrary, GC seems to be the result of a deficit in visual memory replaced by the semantic translation of isolated parts of the ROCF along with a source monitoring deficit.