Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD.

PURPOSE: The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available. METHODS: We retrospectively selected 25 patients with late-onset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1 ± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). RESULTS: Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD- patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule. CONCLUSION: These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.

Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson's disease.

PURPOSE: Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated. METHODS: Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side. RESULTS: Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH. CONCLUSION: These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.

Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study.

PURPOSE: To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). METHODS: Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. RESULTS: As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. CONCLUSION: The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate-precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD.

Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson's disease patients: a [I-123]FP-CIT SPECT study.

To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug-naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I-123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS-VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS-EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS-III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro-putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies.

Amnestic mild cognitive impairment in Parkinson's disease: a brain perfusion SPECT study.

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD-MCI). Perfusion single photon emission computed tomography was performed in 15 PD-MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS-III scores were considered as confounding variables. PD-MCI group (P < 0.05, false discovery rate-corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI-PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI-PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal-parietal-occipital region, including middle occipital and superior temporal gyri, and cuneus-precuneus, as compared to PD. aMCI versus PD-MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD-MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies.

Principal component analysis of FDG PET in amnestic MCI.

PURPOSE: The purpose of the study is to evaluate the combined accuracy of episodic memory performance and (18)F-FDG PET in identifying patients with amnestic mild cognitive impairment (aMCI) converting to Alzheimer's disease (AD), aMCI non-converters, and controls. METHODS: Thirty-three patients with aMCI and 15 controls (CTR) were followed up for a mean of 21 months. Eleven patients developed AD (MCI/AD) and 22 remained with aMCI (MCI/MCI). (18)F-FDG PET volumetric regions of interest underwent principal component analysis (PCA) that identified 12 principal components (PC), expressed by coarse component scores (CCS). Discriminant analysis was performed using the significant PCs and episodic memory scores. RESULTS: PCA highlighted relative hypometabolism in PC5, including bilateral posterior cingulate and left temporal pole, and in PC7, including the bilateral orbitofrontal cortex, both in MCI/MCI and MCI/AD vs CTR. PC5 itself plus PC12, including the left lateral frontal cortex (LFC: BAs 44, 45, 46, 47), were significantly different between MCI/AD and MCI/MCI. By a three-group discriminant analysis, CTR were more accurately identified by PET-CCS + delayed recall score (100%), MCI/MCI by PET-CCS + either immediate or delayed recall scores (91%), while MCI/AD was identified by PET-CCS alone (82%). PET increased by 25% the correct allocations achieved by memory scores, while memory scores increased by 15% the correct allocations achieved by PET. CONCLUSION: Combining memory performance and (18)F-FDG PET yielded a higher accuracy than each single tool in identifying CTR and MCI/MCI. The PC containing bilateral posterior cingulate and left temporal pole was the hallmark of MCI/MCI patients, while the PC including the left LFC was the hallmark of conversion to AD.

The Alzheimer's disease metabolic brain pattern in mild cognitive impairment.

We investigated the expression of the Alzheimer's disease-related metabolic brain pattern (ADRP) in 18F-FDG-PET scans of 44 controls, 27 patients with mild cognitive impairment (MCI) who did not convert to Alzheimer's disease (AD) after five or more years of clinical follow-up, 95 MCI patients who did develop AD dementia on clinical follow-up, and 55 patients with mild-to-moderate AD. The ADRP showed good sensitivity (84%) and specificity (86%) for MCI-converters when compared to controls, but limited specificity when compared to MCI non-converters (66%). Assessment of 18F-FDG-PET scans on a case-by-case basis using the ADRP may be useful for quantifying disease progression.

Care pathways models and clinical outcomes in Disorders of consciousness.

OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by asking 90 patients' caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received. RESULTS: Seventy-three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diagnosis. In long-term care units, the diagnosis at admission and the number of caregivers available for each patient (median value = 3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non-Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. CONCLUSION: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and actions are needed to guarantee equity and standardization of the care process in all European countries.

Metabolic correlates of Rey auditory verbal learning test in elderly subjects with memory complaints.

We evaluated the brain metabolic correlates of main indexes of a widely used word list learning test, the Rey Auditory Verbal Memory Test (RAVLT), in a group of elderly subjects with memory complaints. Fifty-four subjects (age: 72.02 ± 7.45; Mini-Mental State Examination (MMSE) score: 28.9 ± 1.24) presenting at a memory clinic complaining of memory deficit, but not demented, and thirty controls (age: 71.87 ± 7.08; MMSE score: 29.1 ± 1.1) were included. Subjects with memory complaints included both patients with (amnestic mild cognitive impairment, aMCI) and without (subjective memory complaints, SMC) impairment on memory tests. All subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), analyzed with statistical parametric. Patients with aMCI but not those with SMC showed the expected posterior cingulate-precuneus and parietal hypometabolism as compared to controls. Correlation was determined for between four indexes of the RAVLT and brain metabolism. The results show a significant correlation between the delayed recall score and metabolism in posterior cingulate gyrus of both hemispheres and in left precuneus, as well as between a score of long-term percent retention and metabolism in left posterior cingulate gyrus, precuneus, and orbitofrontal areas. These correlations survived correction for age, education, and MMSE score. No correlation was found between immediate or total recall scores and glucose metabolism. These data show the relevant role of posterior cingulate-precuneus and orbitofrontal cortices in retention and retrieval of de-contextualized verbal memory material in a group of elderly subjects with memory complaints and shed light on the topography of synaptic dysfunction in these subjects, overlapping that found in the earliest stages of Alzheimer-type neurodegeneration.

Unawareness of memory deficit in amnestic MCI: FDG-PET findings.

To unveil the brain metabolic correlates of (un)awareness of memory deficit in subjects with amnestic mild cognitive impairment (aMCI), forty-two outpatients underwent brain 18F-FDG-PET. Awareness of memory deficit was assessed with the Memory Complaint Questionnaire (MAC-Q), identifying two groups: low (MCI/unaware; 17 patients) and good (MCI/aware; 25 patients) aMCI awareness. Twenty-nine age-matched healthy subjects represented the control group. SPM2 was used to assess the correlation between brain metabolism and MAC-Q score, for comparisons between each patient group and controls, and between aMCI/unaware and aMCI/aware groups. The two aMCI groups were comparable in terms of age, gender, education, depression, and neuropsychological tests scores. In the whole 42-patient group, a positive correlation was found between MAC-Q score and metabolism in posterior cingulate cortex in both hemispheres and in inferior parietal lobule, middle cingulate cortex, precuneus and angular gyrus in the left hemisphere. Compared to controls, hypometabolism was found in aMCI/unaware in three large clusters, including precuneus, inferior parietal lobule and superior occipital gyrus, in the left hemisphere, and in inferior parietal lobule, angular gyrus and middle temporal gyrus in the right hemisphere. Smaller clusters of hypometabolism were found in bilateral temporal lobe in aMCI/aware. Hypometabolism in inferior parietal lobule, angular gyrus and superior temporal gyrus in the left hemisphere was highlighted in aMCI/unaware versus aMCI/aware. The significant correlation in all 42 aMCI patients points to posteromedial cortex as a key node of the network being involved in awareness of memory deficit. Patients with low awareness show a more severe hypometabolic pattern, typical of Alzheimer's disease and therefore could be more at risk of developing dementia.

Impaired access to semantic memory for the cognition of geographic space in Alzheimer's disease.

This study explores the possibility to capitalize from a widely used semantic fluency test, in order to investigate aspects of topographical space representation, still poorly studied in neurodegenerative diseases. Twenty-six patients with mild Alzheimer's disease (AD) and 13 healthy control (CTR) subjects underwent neuropsychological assessment at baseline (T0) and about 2 years later (T1). The cities named during category verbal fluency test ("names of cities") were marked on a map, and the polygon perimeter obtained by joining the external points was computed. Mini-mental state examination (MMSE) score, number of cities named and perimeter length were compared between T0 and T1, both within-group and between groups. MMSE score and number of cities significantly differed between AD and CTR both at T0 and at T1; perimeter length differed significantly only at T1. Between T0 and T1, all the three parameters significantly decreased in AD, while they were substantially unchanged in CTR. Besides a reduction of semantic verbal fluency, there seems to be a 'restriction' of mental geographic space representation already in mild AD. These findings should be confirmed and exploited by further ad hoc investigations.

SPECT predictors of cognitive decline and Alzheimer's disease in mild cognitive impairment.

Baseline brain single photon emission computed tomography (SPECT) was evaluated in eighty subjects with mild cognitive impairment (MCI) who were followed for a mean of about two years, when twelve patients developed Alzheimer's disease (AD), nineteen showed memory decline (D), and forty-three had normal cognition assessment (stable: S) (six drop-out). Volumetric Regions of Interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures showed significant effects for both the group (S, D, and AD; p < 0.004) and VROI (p < 0.0001) factors, with significant group*region interaction (p < 0.01). At post-hoc comparison, hippocampal VROIs values were lower in AD than in D and S, while parietal VROIs values were lower in D and AD than in S. These four VROI significantly correlated with verbal delayed recall score at follow-up visit. Receiver operating characteristic (ROC) curves for the mean hippocampal VROI value showed 0.81 sensitivity with 0.86 specificity in separation of S+D from AD (p < 0.0001), and 0.69 sensitivity with 0.75 specificity in separation of S from D+AD (p < 0.0002). ROC curves for the mean parietal VROI value showed 0.62 sensitivity with 0.70 specificity in separation of S from D+AD (p < 0.0002). Baseline SPECT can support outcome prediction in subjects with MCI.

Stroop interference task and single-photon emission tomography in anorexia: a preliminary report.

OBJECTIVE: The aim of this preliminary study was to investigate the physiologic substrate of executive function in anorexia nervosa (AN) by assessing the relation between brain perfusion and Stroop interference task (SIT). METHOD: The classical SIT test and brain single-photon emission tomography (SPET) were evaluated in 16 AN females (mean age = 23.69 +/- 8.68 years; mean body mass index [BMI] = 16.19 +/- 1.53 kg/m2). The relation between the two examinations was searched by statistical parametric mapping (SPM 99) with a height threshold of p = .001. RESULTS: An abnormally low or a borderline SIT value was found in 25% of patients. A significant correlation between the SIT score and brain perfusion was found in the superior frontal gyrus of both hemispheres (Brodmann's area [BA] 6 in both hemispheres and BA 8 in the right hemisphere). No correlation was found in the anterior cingulate gyrus. CONCLUSION: BA 6 and BA 8 and the anterior cingulate are believed to be the basis of both error detection and immediate correction. Activity of BA 6 and BA 8 reflects this executive task in AN patients as well, whereas the lack of correlation in the anterior cingulate may suggest its blunted activity in AN patients, similarly to what is shown in other conditions characterized by impaired executive function, such as patients with depression, patients with schizophrenia, and abstinent drug abusers. However, these findings should still be quoted as preliminary, given some limitations of the study design, such as the lack of a control group, and the unfeasibility of controlling some relevant confounding variables, such as psychiatric comorbidity, medication, and the time interval between examinations, mainly deriving from the relatively few patients studied.