Despite brain perfusion SPECT with technetium radiopharmaceuticals has not been formally included among the biomarkers for the early diagnosis of Alzheimer's disease (AD), its worldwide availability and the large literature evidence in AD and related disorders still make of it a valid alternative to FDG-PET, wherever the latter is unavailable. In this article, baseline brain SPECT has been evaluated in 80 subjects presenting with a cognitive complaint who have been followed for a mean of about two years, when twelve patients developed AD-dementia (AD-D), nineteen showed significant memory decline (D), and forty-three had normal cognition assessment (stable: S), while six patients dropped-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-D; 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-D than in D and S, while parietal VROIs values were lower in D and AD-D 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-D (p < 0.0001), and 0.69 sensitivity with 0.75 specificity in separation of S from D + AD-D (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-D (p < 0.0002). Baseline SPECT can support outcome prediction in subjects with MCI and assist clinicians in identifying MCI patients with biological signs of neurodegeneration of the AD-type in critical cortical areas.
Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood.
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.
Patients with Mild Cognitive Impairment (MCI) not converted to dementia at one to three years follow-up represent a heterogeneous group across studies, by including 'late converters' but also patients without any neurodegenerative disease. We tested the hypothesis that the combination of memory and brain metabolic assessment could identify subgroups of memory decliners (MCI/Decl) and non-decliners (MCI/noDecl) before a long follow-up time is available. From twenty-nine patients with amnestic MCI (aMCI) at baseline, three groups were identified at follow-up: 10 patients who converted to AD (MCI/AD); 10 patients either showing episodic memory worsening or reaching the floor effect on memory and declining in other key tests (MCI/Decl) and 9 patients showing no memory worsening or even improvement (MCI/noDecl). They were compared with a group of fourteen elderly controls (CTR) by means of basal FDG-PET voxel-based analysis (SPM2). Two hypometabolic clusters were found in MCI/AD versus CTR, including the bilateral posterior cingulate cortex, the left parietal precuneus and the left fusiform gyrus. MCI/AD showed also a large hypometabolic region, mainly including the left medium and superior temporal gyri and inferior parietal lobule, when compared to MCI/noDecl. The MCI/Decl showed a hypometabolic region in the left medial temporal lobe versus both CTR (hippocampus) and MCI/noDecl (parahippocampal gyrus and hippocampus). No significant difference was found in the comparison between CTR and MCI/noDecl, neither in the comparison between MCI/Decl and MCI/AD. Thus, non converter MCI patients comprised a sub-group of 'decliners' with AD-like metabolic and cognitive patterns, likely including 'late converters', and a sub-group lacking this pattern, with stable or improving memory function and a brain metabolic picture similar to that in healthy controls. Combining neuropsychological and FDG-PET information could be used for prognostic purposes in aMCI patients at medium-term follow-up.
Chorea, cognitive decline, and psychiatric symptoms are shared by Huntington's disease (HD) and similar conditions called HD phenocopies. We describe the first case reported in Italy of Huntington disease-like 2 (HDL2), clinically and radiologically indistinguishable from HD, showing the importance of considering African ancestry in the diagnostic process.
