Low thalamic activity during a digit-symbol substitution task is associated with symptoms of subjective cognitive decline.

Introduction: Subjective cognitive decline (SCD) may represent the earliest preclinical stage of Alzheimer's Disease (AD) for some older adults. However, the underlying neurobiology of SCD is not completely understood. Since executive function may be affected earlier than memory function in the progression of AD, we aimed to characterize SCD symptoms in terms of fMRI brain activity during the computerized digit-symbol substitution task (DSST), an executive function task. We also explored associations of DSST task performance with brain activation, SCD severity, and amyloid-ß (Aß) load. Methods: We analyzed data from 63 cognitively normal older individuals (mean age 73.6 ± 7.2) with varying degree of SCD symptoms. Participants completed a computerized version of DSST in the MR scanner and a Pittsburgh Compound-B (PiB)-PET scan to measure global cerebral Aß load. Results: A voxel-wise analysis revealed that greater SCD severity was associated with lower dorsomedial thalamus activation. While task performance was not associated with brain activation nor Aß load, slower reaction time was associated with greater SCD severity. Discussion: The observed lower dorsomedial thalamus activation may reflect declining familiarity-based working memory and the trans-thalamic executive function pathway in SCD. SCD symptoms may reflect altered neural function and subtle decline of executive function, while Aß load may have an indirect impact on neural function and performance. Self-perceived cognitive decline may serve as a psychological/subjective marker reflecting subtle brain changes.

An Effect of Education on Memory-Encoding Activation in Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) may be an early manifestation of pre-clinical Alzheimer's disease. Elevated amyloid-ß (Aß) is a correlate of SCD symptoms in some individuals. The underlying neural correlates of SCD symptoms and their association with Aß is unknown. SCD is a heterogeneous condition, and cognitive reserve may explain individual differences in its neural correlates. OBJECTIVE: We investigated the association between brain activation during memory encoding and SCD symptoms, as well as with Aß, among older individuals. We also tested the moderating role of education (an index of cognitive reserve) on the associations. METHODS: We measured brain activation during the "face-name" memory-encoding fMRI task and Aß deposition with Pittsburgh Compound-B (PiB)-PET among cognitively normal older individuals (n = 63, mean age 73.1 ± 7.4 years). We tested associations between activation and SCD symptoms by self-report measures, Aß, and interactions with education. RESULTS: Activation was not directly associated with SCD symptoms or Aß. However, education moderated the association between activation and SCD symptoms in the executive control network, salience network, and subcortical regions. Greater SCD symptoms were associated with greater activation in those with higher education, but with lower activation in those with lower education. CONCLUSION: SCD symptoms were associated with different patterns of brain activation in the extended memory system depending on level of cognitive reserve. Greater SCD symptoms may represent a saturation of neural compensation in individuals with greater cognitive reserve, while it may reflect diminishing neural resources in individuals with lower cognitive reserve.

Brain imaging in the differential diagnosis of young-onset dementias.

Young-onset dementia is a broad category of diseases that affect adults before the age of 65, with devastating effects on individuals and families. Neuroimaging plays a clear and ever-expanding role in the workup of these diseases. MRI demonstrates classic patterns of atrophy that help to confirm the clinical diagnosis and may predict the underlying disease. Functional nuclear imaging, such as PET, demonstrates areas of brain dysfunction even in the absence of visible atrophy. These techniques can inform important aspects of the care of young-onset dementia, such as the underlying pathologic condition, treatment, and prognosis.