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Self-perceived word-finding difficulties are common in aging individuals as well as in Alzheimer's Disease (AD). Language and speech deficits are difficult to objectify with neuropsychological assessments. We therefore aimed to investigate whether amyloid, an early AD pathological hallmark, is associated with speech-derived semantic complexity. We included 63 individuals with subjective cognitive decline (age 64 ± 8, MMSE 29 ± 1), with amyloid status (positron emission tomography [PET] scans n = 59, or Aβ 1-42 cerebrospinal fluid [CSF] n = 4). Spontaneous speech was recorded using three open-ended tasks (description of cookie theft picture, abstract painting and a regular Sunday), transcribed verbatim and subsequently, linguistic parameters were extracted using T-scan computational software, including specific words (content words, frequent, concrete and abstract nouns, and fillers), lexical complexity (lemma frequency, Type-Token-Ratio) and syntactic complexity (Developmental Level scale). Nineteen individuals (30%) had high levels of amyloid burden, and there were no differences between groups on conventional neuropsychological tests. Using multinomial regression with linguistic parameters (in tertiles), we found that high amyloid burden is associated with fewer concrete nouns (OR middle (95%CI): 7.6 (1.4–41.2), OR lowest : 6.7 (1.2–37.1)) and content words (OR lowest : 6.3 (1.0–38.1). In addition, we found an interaction for education between high amyloid burden and more abstract nouns. In conclusion, high amyloid burden was modestly associated with fewer specific words, but not with syntactic complexity, lexical complexity or conventional neuropsychological tests, suggesting that subtle spontaneous speech deficits might occur in preclinical AD. • High amyloid burden was associated with fewer specific words during spontaneous speech. • Amyloid burden was not associated with conversation fillers and type-token ratio. • Amyloid burden was not associated with fluency or confrontational naming. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. Methods: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona). Analysis of covariance models with samples and cerebrospinal fluid biomarkers as between‐subject factors were calculated. Results: A significant main effect for AD biomarker (Aβ42− > Aβ42+) in the left medial temporal lobe (MTL) was found, with the absence of main effects for sample or interaction effects between AD biomarker and sample. This indicates consistent lower left MTL volume across three samples in SCD subjects with abnormal Aβ42 levels. Discussion: Our results support the model that in the presence of AD pathology, SCD corresponds to the late preclinical stage (stage 2 of AD) with smaller MTL volumes. [ABSTRACT FROM AUTHOR]

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2–8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini–Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05 FDR ). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Cognitive reserve (CR) explains interindividual differences in the ability to maintain cognitive function in the presence of neuropathology. We developed a neuroimaging approach including a measure of brain atrophy and cognition to capture this construct. In a group of 511 Alzheimer's disease (AD) biomarker-positive subjects in different stages across the disease spectrum, we performed 3T magnetic resonance imaging and predicted gray matter (GM) volume in each voxel based on cognitive performance (i.e. a global cognitive composite score), adjusted for age, sex, disease stage, premorbid brain size (i.e. intracranial volume) and scanner type. We used standardized individual differences between predicted and observed GM volume (i.e. W-scores) as an operational measure of CR. To validate this method, we showed that education correlated with mean W-scores in whole-brain ( r = −0.090, P < 0.05) and temporoparietal ( r = −0.122, P < 0.01) masks, indicating that higher education was associated with more CR (i.e. greater atrophy than predicted from cognitive performance). In a voxel-wise analysis, this effect was most prominent in the right inferior and middle temporal and right superior lateral occipital cortex ( P < 0.05, corrected for multiple comparisons). Furthermore, survival analyses among subjects in the pre-dementia stage revealed that the W-scores predicted conversion to more advanced disease stages (whole-brain: hazard ratio [HR] = 0.464, P < 0.05; temporoparietal: HR = 0.397, P < 0.001). Our neuroimaging approach captures CR with high anatomical detail and at an individual level. This standardized method is applicable to various brain diseases or CR proxies and can flexibly incorporate different neuroimaging modalities and cognitive parameters, making it a promising tool for scientific and clinical purposes. Hum Brain Mapp 38:4703-4715, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD). Methods We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume–corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains. Associations were investigated using linear regression analyses. Results In the whole sample, reduced overall and regional CBF was associated with impairment in all cognitive domains. We found significant interactions between diagnosis and CBF for language and between diagnosis and parietal CBF for global cognition and executive functioning. Stratification showed that decreased CBF was associated with worse performance in AD patients but not in MCI or SCD. Discussion Our results suggest that CBF may have potential as a functional marker of disease severity. [ABSTRACT FROM AUTHOR]