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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.

The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer's Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer's disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.

Background and purpose: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. Methods: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology – Società Italiana di Neurologia per le Demenze; neuroradiology – Associazione Italiana di Neuroradiologia; biochemistry – Società Italiana di Biochimica Clinica; psychogeriatrics – Associazione Italiana di Psicogeriatria; nuclear medicine – Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N–1 majority defined consensus achievement. Results: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes(yes-no-abstained): 3-1-1); 18F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer’s disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer’s disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). Conclusions: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.