Amyloid Deposition and Cognition in Older Adults: The Effects of Premorbid Intellect

Abstract

Although amyloid deposition remains a marker of the development of Alzheimer's disease, results linking amyloid and cognition have been equivocal. Twenty-five community-dwelling non-demented older adults were examined with (18)F-flutemetamol, an amyloid imaging agent, and a cognitive battery, including an estimate of premorbid intellect and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the first model, (18)F-flutemetamol uptake significantly correlated with the Delayed Memory Index of the RBANS (r = -.51, p = .02) and premorbid intellect (r = .43, p = .03). In the second model, the relationship between (18)F-flutemetamol and cognition was notably stronger when controlling for premorbid intellect (e.g., three of the five RBANS Indexes and its Total score significantly correlated with (18)F-flutemetamol, r's = -.41 to -.58). Associations were found between amyloid-binding (18)F-flutemetamol and cognitive functioning in non-demented older adults. These associations were greatest with delayed memory and stronger when premorbid intellect was considered, suggesting that cognitive reserve partly compensates for the symptomatic expression of amyloid pathology in community-dwelling elderly.

Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults

“…As the current sample exhibited delayed memory and total cognition abilities approximately 1.0 SD and 0.5 SD lower than the participants in Duff et al’s previous study, 17 respectively, the differences in severity of impairment may account for these discrepant findings. In essence, our study may have contained more individuals whose memory difficulties were beyond the threshold of receiving a benefit from cognitive reserve, 52 thus reducing the mediational effect observed in Duff et al’s earlier study.…”

“…16 Similarly, although Duara and colleagues 14 identified differences in [18F]flutemetamol uptake between cognitively intact, MCI, and AD participants, the relationships between amyloid accumulation and episodic memory or verbal fluency were nonsignificant among all 3 groups. Conversely, Duff and colleagues 17 observed that increased [18F]flutemetamol binding was significantly associated with decreases in delayed memory, visual spatial construction, and language in nondemented adults (MCI and normal cognition), with this relationship being further strengthened when factoring in premorbid intellectual functioning.…”

Relationship between 18F-Flutemetamol uptake and RBANS performance in non-demented community-dwelling older adults

“…Exclusion criteria included an ICD-10 diagnosis of dementia; medical comorbidities likely to affect cognition (e.g., history of major neurological disorders including strokes, brain lesions, head injury with loss of consciousness >30 minutes, radiation therapy to the brain, major psychiatric disorders [schizophrenia, bipolar disorder, severe major depressive disorder], or substance abuse); and use of anticonvulsant, antipsychotic, cognitive-enhancing, or cholinesterase-inhibiting medications. Of note, 19 of our 27 participants were also included in the Duff et al (2013) study, though the results presented in the current study reflect unique and updated cognitive data and 18 F-Flutemetamol amyloid-PET scans. This study followed an observational design, and sampling procedures were based on convenience sampling.…”

“…Finally, only one study to date has evaluated performance on the RBANS with amyloid-PET imaging modalities. Duff et al (2013) identified that worse performances on RBANS Indexes of Delayed Memory, Visuospatial/Constructional, and Language were associated with increased amyloid burden using 18 F-Flutemetamol-PET in non-demented participants (healthy controls and MCI), and this relationship was further strengthened when factoring in premorbid intellectual functioning.…”

“…With the increased emphasis of amyloid assessment in AD research, attempting to replicate previous findings is necessary to better characterize and validate the relationship between RBANS performance and amyloid deposition/accumulation. This is particularly true since at the time of the Duff (2013) study, 18 F-Flutemetamol was still an experimental ligand; since that time, 18 F-Flutemetamol has received Federal Drug Administration (FDA) approval (Vizamyl; GE Healthcare, Wauwatosa, WI) and the methodology for uptake quantification has undergone much greater scientific rigor than what was used previously. As a result, replication will be important to limit the potential for spurious findings based on a single study.…”