Cerebral beta-amyloidosis and neurodegeneration among people with normal cognitive function aged 50–89 years

As preclinical Alzheimer's disease becomes a target for therapeutic intervention, the overlap between imaging abnormalities associated with typical ageing and those associated with Alzheimer's disease needs to be recognised.
Researchers have characterised how typical ageing and preclinical Alzheimer's disease overlap in terms of beta-amyloidosis and neurodegeneration.

Researchers measured age-specific frequencies of amyloidosis and neurodegeneration in individuals with normal cognitive function aged 50–89 years.
Potential participants were randomly selected from the Olmsted County ( MN, USA ) population-based study of cognitive ageing and invited to participate in cognitive and imaging assessments.
To be eligible for inclusion, individuals must have been judged clinically to have no cognitive impairment and have undergone amyloid PET, 18F-fluorodeoxyglucose ( 18F-FDG ) PET, and MRI.

Imaging results were obtained during the period 2006-2013.

Amyloid status ( positive [ A+ ] or negative [ A– ] ) was determined by amyloid PET with 11C Pittsburgh compound B. Neurodegeneration status ( positive [ N+ ] or negative [ N– ] ) was determined by an Alzheimer's disease signature 18F-FDG PET or hippocampal volume on MRI.

Researchers determined age-specific frequencies of the four groups ( amyloid negative and neurodegeneration negative [ A–N– ], amyloid positive and neurodegeneration negative [ A+N– ], amyloid negative and neurodegeneration positive [ A–N+ ], or amyloid positive and neurodegeneration positive [ A+N+ ] ) cross-sectionally using multinomial regression models.
Associations of group frequencies with APOE epsilon-4 status ( assessed with DNA extracted from blood ) and sex were also investigated.

The study population consisted of 985 eligible participants.

The population frequency of A–N– was 100% ( n=985 ) at age 50 years and fell to 17% ( 95% CI 11–24 ) by age 89 years.
The frequency of A+N– increased to 28% ( 24–32 ) at age 74 years, then decreased to 17% ( 11–25 ) by age 89 years.
The frequency of A–N+ increased from age 60 years, reaching 24% ( 16–34 ) by age 89 years.
The frequency of A+N+ increased from age 65 years, reaching 42% ( 31–52 ) by age 89 years.

The results from multinomial models suggest that A+N– and A+N+ were more frequent in APOE epsilon4 carriers than in non-carriers and that A+N+ was more, and A+N– less frequent in men than in women.

In conclusion, the accumulation of amyloid and neurodegeneration are nearly inevitable by old age, but many people are able to maintain normal cognitive function despite these imaging abnormalities.
Changes in the frequency of amyloidosis and neurodegeneration with age, which seem to be modified by APOE epsilon4 and sex, suggest that pathophysiological sequences might differ between individuals. ( Xagena )

Clifford RJ Jr et al, Lancet Neurology 2014; 13: 997–1005



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