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In the news: Genetics & AREDS Supplements; Antioxidants & Cataract Risk; Predicting Future Memory Deficits

To Test or Not to Test? That is the Question

Two genes consistently shown to have the strongest associations with AMD risk are the complement factor H (CFH) gene and the Age-Related Maculopathy Susceptibility 2 gene (ARMS2). Both genes have been evaluated in studies asking whether genotype in high-risk AREDS participants influences the response to treatment with zinc and/or antioxidants. The results and conclusions of these studies differ greatly.

In brief, one paper (Klein et al) (1) reports that all CFH genotypes (both high and low risk) benefited from zinc and antioxidants, and found no association between AREDS treatment assignment and having ARMS2 risk alleles. The authors concluded that their results did not justify routine genetic screening.

The second (Awh et al) (2) reports an increased risk of disease progression associated with zinc treatment in CFH risk genotypes, and a deleterious response associated with antioxidant supplements in those with ARMS2 risk genotypes. The study authors recommend routine genetic testing in AMD, and customizing AREDS supplements based on genotype. 

At the 2013 American Academy of Opthalmology annual meeting, Dr. Emily Chew of the National Eye Institute indicated that analysis of the Awh et al study reveals that it was insufficiently powered to show statistical significance (3). She added that the AREDS Research Group recently explored interactions between genotype and treatment assignments in AREDS category 3 and categories 3 and 4 patients. No significant differences were seen.

Dr. Chew also pointed out that The American Academy of Ophthalmology Task Force on Genetic Testing (4) recommends avoiding routine genetic testing for genetically complex disorders like AMD until specific treatment or surveillance strategies have been shown in published trials to benefit individuals with specific genotypes.

So, to test or not to test? The answer seems clear for the moment: Until more research is conducted, it’s premature to do routine genetic testing of AMD patients and to customize AREDS supplements based on the results.

• Read more about these studies and the issue of genetic testing in AMD

Antioxidants Linked to Lower Cataract Risk

A prospective, population-based study from Sweden is the first of its kind to investigate the association between all antioxidants in the diet and age-related cataract (5).  Previous studies have focused on individual dietary or supplemental antioxidants. The Swedish researchers instead examined total antioxidant capacity (TAC), which measures the capacity from all antioxidants in the diet and takes into account their synergistic effects.  

Looking at the diets of more than 30,000 women (aged 49-83) followed for over 7 years, they found that those consuming the most antioxidants (mainly through fruits, vegetables, whole grains and coffee) had a 13% lower risk of developing age-related cataract. Though women who ate more antioxidants tended to be more educated and less likely to smoke, the association of high TAC and cataract incidence was consistent across subgroups based on potential risk factors and sources of oxidative stress.

A new, comprehensive review (6) on nutrition and cataracts lends support to the ‘TAC’ approach taken by the Swedish team. The review points out that with observational data “it’s been difficult to tease apart the effects of single – or even groups of a few – nutrients, suggesting there may be synergistic effects of multiple nutrients with regard to lens health”.

Early Warning for Future Memory Problems?

When memory starts to slip in older adults, is it more likely due to normal aging or a harbinger of conditions such as mild cognitive impairment (MCI) or Alzheimer’s (AD)?  

Cornell University scientists have published a study (7,8) assessing a method to distinguish memory loss associated with healthy aging from more serious memory problems, years before symptoms emerge.

Employing advanced dual-retrieval models of recall that use clinical data for testing hypotheses about MCI and AD, the investigators looked at two types of memory processes – reconstructive and recollective – in healthy subjects and those with cognitive impairment.

Reconstructive memory is recalling an event by piecing together clues about its meaning, while recollective memory is recalling a word or event exactly.

The researchers found that declines in recollective memory were a feature of normal aging. Declines in reconstructive memory, however, were associated with MCI and AD, and not with healthy aging. They found no evidence of further reconstructive memory decline after age 69 in samples of nationally representative older adults.

The authors conclude that over periods of 1½ - 6 years, declines in reconstructive memory processes are accurate predictors of future conversion to MCI and AD – even better predictors than the best genetic marker of these conditions.

References

1. Klein ML et al. CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmol 115:1019-1025, 2008.
2. Awh CW et al. CFH and ARMS2 Genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmol Aug. 20, 2013 [Epub ahead of print].
3. Renshaw RM. Debate over the value of genetic markers for AMD continues. Retina Today Dec, 2013.
4. AAO Task Force on Genetic Testing. Recommendations for Genetic Testing of Inherited Eye Diseases: Report of the American Academy of Ophthalmology Task Force on Genetic Testing—2012. Ophthalmol 119:2408-2410, 2012
5. Rautiainen, Susanne, et al. "Total Antioxidant Capacity of the Diet and Risk of Age-Related Cataract: A Population-Based Prospective Cohort of Women." JAMA ophthalmology 132:247-252, 2014.
6. Weikel KA et al. Review. Nutritional modulation of cataract. Nutr Rev 72:30–47, 2014.
7. Brainerd CJ et al. Dual-retrieval models and neurocognitive impairment, J Exp Psychol Learn Mem Cogn 40:41-65, 2014.
8. Jacobs AR. A simple way to distinguish memory loss from cognitive impairment. Medscape Nov 12, 2013.