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Perrotin A, Mormino EC, Madison CM, Hayenga AO, Jagust WJ. Subjective cognition and amyloid deposition imaging: a Pittsburgh Compound B positron emission tomography study in normal elderly individuals. Arch Neurol. 2012 Feb;69(2):223-9. PubMed.
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University of California, San Francisco
The study by Perrotin et al. shows that subtle decreases in memory and an accompanying awareness of reduced memory performance is associated with higher PIB-PET imaging of β amyloid (Aβ) in the brains of asymptomatic, cognitively normal elders. In view of the recent definition of preclinical AD proposed by the NIA-AA work group stating that subtle cognitive deficits in the presence of Aβ biomarker(s) are signs of AD at an early disease stage, the current results gain stature: Subjective complaints about subtle memory decline may hint towards underlying AD pathology and future AD dementia. However, it should be taken into account that the association between Aβ and cognition in asymptomatic, cognitively normal subjects is relatively weak across different studies, and in the current study, only few out of many measures of cognitive performance and cognitive complaints were correlated with Aβ. These results stimulate further research on the important questions of what such subtle cognitive and brain changes mean for the prognosis of AD dementia in the long term, and what factors drive the clinical progression in subjects with elevated Aβ.
Brigham and Women's Hospital
Perrotin et al. present very interesting work. Their cross-sectional findings suggest that there is a relationship between subjective cognitive complaint (SCC) and amyloid deposition in cognitively normal older individuals, a finding that has not been shown previously. Importantly, they controlled for depressive symptoms in their model, a potential confounding factor that has not always been considered when investigating SCCs in prior studies. No relationships were found between SCC and objective cognitive measures, suggesting that SCC provides unique information not captured by standardized neuropsychological tests.
This study posits that SCCs may be helpful in detecting some of the earliest changes due to Alzheimer’s disease (AD), which has clear implications for future secondary prevention trials. However, the study found that only one general memory question was associated with amyloid accumulation, which limits the interpretation and application of the findings. It will be important to follow up this study with a more extensive survey of SCCs to determine which specific complaints are associated with increased risk for AD to better understand the earliest cognitive changes that may represent preclinical AD.
Karolinska Institutet
This paper focuses on a very important issue, namely, whether subjective cognition might be a very early sign for existing brain pathology leading to Alzheimer's disease.
Since the subject population was quite old (above 70) and very highly educated, it would be interesting to continue these studies in younger subjects (40-60 years) with subjective memory complaints. Interestingly enough, regions known for early high PIB retention, such as the right medial prefrontal cortex and precuneus, were related to self-reports of general memory complaint. The observations may again underline the importance of subjective memory complaint in the future of very early preventive intervention in AD. The authors speculate that the subjective cognition problems may have a duration of 15 years, and that β amyloid at that point reaches a plateau, but it has to be remembered that PIB imaging studies in mild MCI show an increase in PIB retention at follow-up to severe MCI (Kadir et al., 2012). If subjective cognitive impairment represents a very early stage of AD, it is important to try to develop sensitive single-episodic memory tests for clinical screening. The next important step is, of course, to know how the CSF biomarkers relate to subjective memory.
References:
Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Långström B, Nordberg A. Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease. Neurobiol Aging. 2012 Jan;33(1):198.e1-14. PubMed.
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