Background/Aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level. Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.

Previous studies with functional magnetic resonance imaging (fMRI) demonstrated a differential brain activity and connectivity after treatment with donepezil in Alzheimer's disease (AD) when compared to healthy elders. Importantly however, there are no available studies where the placebo or control group included comparable AD patients relative to the treated groups. Fifteen patients recently diagnosed of AD were randomized to treatment (n = 8) or to control group (n = 7); the former receiving daily treatment of donepezil during 3 months. At baseline and follow-up, both groups underwent resting-state as well as task-fMRI examinations, this latter assessing encoding of visual scenes. The treated group showed higher connectivity in areas of the default mode network, namely the right parahippocampal gyrus at follow-up resting-fMRI as compared to the control group. On the other hand, for the task-fMRI, the untreated AD group presented progressive increased activation in the left middle temporal gyrus and bilateral precuneus at the 3-month examination compared to baseline, whereas the treated group exhibited stable patterns of brain activity. Donepezil treatment is associated with stabilization of connectivity of medial temporal regions during resting state and of brain efficiency during a cognitive demand, on the whole reducing progressive dysfunctional reorganizations observed during the natural course of the disease.

Background and purpose Several diagnostic biomarkers are currently available for clinical use in early‐onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. Methods There were a total of 40 subjects with early‐onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non‐neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid‐positron emission tomography (PET) and 18F‐fluorodeoxyglucose‐PET were performed. Neurologists provided pre‐ and post‐biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure. Results Cerebrospinal fluid biomarkers and amyloid‐PET increased diagnostic confidence in AD (77.4%–86.2% after CSF, 92.4% after amyloid‐PET, P < 0.01) and non‐neurodegenerative conditions (53.6%–75% after CSF, 95% after amyloid‐PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated. Conclusions Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early‐onset cognitive impairment.

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