%0 Journal Article %J J Alzheimers Dis %D 2018 %T Prominent Non-Memory Deficits in Alzheimer's Disease Are Associated with Faster Disease Progression. %A Scheltens, Nienke M E %A Tijms, Betty M %A Heymans, Martijn W %A Rabinovici, Gil D %A Cohn-Sheehy, Brendan I %A Miller, Bruce L %A Kramer, Joel H %A Wolfsgruber, Steffen %A Wagner, Michael %A Kornhuber, Johannes %A Peters, Oliver %A Scheltens, Philip %A van der Flier, Wiesje M %X

BACKGROUND: Alzheimer's disease (AD) is a heterogeneous disorder.

OBJECTIVE: To investigate whether cognitive AD subtypes are associated with different rates of disease progression.

METHODS: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses.

RESULTS: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; pinteraction<0.001; CDR sob 1.3±0.1; pinteraction<0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05).

CONCLUSIONS: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.

%B J Alzheimers Dis %8 2018 Aug 03 %G eng %R 10.3233/JAD-171088 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Utility of Amyloid and FDG-PET in Clinical Practice: Differences Between Secondary and Tertiary Care Memory Units. %A Lage, Carmen %A Suarez, Andrea Gonzalez %A Pozueta, Ana %A Riancho, Javier %A Kazimierczak, Martha %A Bravo, María %A Jimenez Bonilla, Julio %A de Arcocha Torres, Marıa %A Quirce, Remedios %A Banzo, Ignacio %A Vázquez-Higuera, José Luis %A Rabinovici, Gil D %A Rodriguez-Rodriguez, Eloy %A Sánchez-Juan, Pascual %X

The clinical utility of amyloid positron emission tomography (PET) has not been fully established. Our aim was to evaluate the effect of amyloid imaging on clinical decision making in a secondary care unit and compare our results with a previous study in a tertiary center following the same methods. We reviewed retrospectively 151 cognitively impaired patients who underwent amyloid (Pittsburgh compound B [PiB]) PET and were evaluated clinically before and after the scan in a secondary care unit. One hundred and fifty concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed changes between the pre- and post-PET clinical diagnosis and Alzheimer's disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using χ2 and multivariate logistic regression. Concordance between classification based on scan readings and baseline diagnosis was 66% for PiB and 47% for FDG. The primary diagnosis changed after PET in 17.2% of cases. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (p < 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (p = 0.0002). Changes in treatment were associated with concordant PiB (p = 0.009) while FDG had no effect on treatment decisions. Based on our regression model, patients with diagnostic dilemmas, a suspected non-amyloid syndrome, and Clinical Dementia Rating <1 were more likely to benefit from amyloid PET due to a higher likelihood of diagnostic change. We found that changes in diagnosis after PET in our secondary center almost doubled those of our previous analysis of a tertiary unit (9% versus 17.2%). Our results offer some clues about the rational use of amyloid PET in a secondary care memory unit stressing its utility in mild cognitive impairment patients.

%B J Alzheimers Dis %V 63 %P 1025-1033 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29710706?dopt=Abstract %R 10.3233/JAD-170985 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Posterior Accumulation of Tau and Concordant Hypometabolism in an Early-Onset Alzheimer's Disease Patient with Presenilin-1 Mutation. %A Smith, Ruben %A Wibom, Moa %A Olsson, Tomas %A Hägerström, Douglas %A Jögi, Jonas %A Rabinovici, Gil D %A Hansson, Oskar %K Adult %K Age of Onset %K Alzheimer Disease %K Amyloid beta-Peptides %K Aniline Compounds %K Benzothiazoles %K Brain %K Brain Mapping %K Fluorodeoxyglucose F18 %K Humans %K Magnetic Resonance Imaging %K Male %K Positron-Emission Tomography %K Presenilin-1 %K Radiopharmaceuticals %K tau Proteins %X

It is unclear whether the distribution of tau pathology differs between cases with early-onset familial Alzheimer's disease (AD) and sporadic AD. We present positron emission tomography (PET) data from a young patient with a presenilin-1 mutation (Thr116Asn). 18F-flutemetamol PET showed a distribution of amyloid-β fibrils similar to sporadic AD. However, the pattern of tau pathology, revealed using 18F-AV1451 PET, showed higher uptake in posterior cingulate, precuneus, parietal and occipital cortices compared to late-onset sporadic AD. Further, the tau pathology, but not amyloid pathology, exhibited a very clear inverse relationship with 18F-fluorodeoxyglucose-metabolism, indicating neuronal hypometabolism in regions affected by tau aggregates.

%B J Alzheimers Dis %V 51 %P 339-43 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836192?dopt=Abstract %R 10.3233/JAD-151004 %0 Journal Article %J J Alzheimers Dis %D 2015 %T Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer's Disease. %A Migliaccio, Raffaella %A Agosta, Federica %A Possin, Katherine L %A Canu, Elisa %A Filippi, Massimo %A Rabinovici, Gil D %A Rosen, Howard J %A Miller, Bruce L %A Gorno-Tempini, Maria Luisa %X

The term early-onset Alzheimer's disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter atrophy in EOAD patients compared to late-onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital, and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate.

%B J Alzheimers Dis %8 2015 Mar 3 %G eng %R 10.3233/JAD-142292