The role of Nutrition in Geriatric Mental Health

1. The role of Nutrition in Geriatric Mental Health Chih-Chiang Chiu, M.D., Ph.D. Department of Psychiatry, Taipei City Psychiatric Center

2. Dementia (Major Neurocognitive Disorder) • Significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on: 1. Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and 2. A substantial impairment in cognitive performance, documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment. • The cognitive deficits interfere with independence in everyday activities

3. Specified: • Alzheimer’s disease • Frontotemporal lobar degeneration • Lewy body disease • Vascular disease • Traumatic brain injury • Substance/medication use • HIV infection • Prion disease • Parkinson’s disease • Huntington’s disease • Another medical condition • Multiple etiologies • Unspecified

4. Prevalence 45- 40- 35- 30- 25- 20- 15- 10- 5- 0- 20% 1.5% 65-69 70-74 75-79 80-84 85-89 90-94 95-99 year-old Alzheimer’s disease • Prevalence estimates for dementia: approximately l%-2% at age 65 yearsand as high as 30% by age 85 yrs • The prevalence rate is doubled every 5 years between age 65-85 years

5. MCI (Minor neurocognitive disorder) Nearly 10% to 15% of a-MCI patients progressing to a diagnosis of probable AD each year, relative to only 1% to 2% of the general elderly population

6. The importance of PUFAs in mental disorder • constitute about 20% of the dry weight of brain, AA and DHA accounted for about 70% • As precursors of many compounds, they are important to the function of nervous system • alter the microenvironment • DHA deficit is associated with dysfunctions of neuronal membrane stability and transmission of monoamine system • EPA is important in balancing the immune function and physical healthy by reducing AA level on cell membrane and PGE2 synthesis

7. Association with cognitive impairment in older people? • Most observational studies showed intake of fish or n-3 PUFAs or levels of n-3 PUFAs may positively associate with lower likelihood of cognitive impairment, declineor dementia • The association seems to be stronger for fish consumption than for n-3 PUFA intake. • APOE ε4, cardiovascular risk, and depression may modify the association. • Some inconsistency exists Solfrizzi et al., Exp Gerontol 2005 Heude et al., Am J Clin Nut 2003 GAO et al., J Nutr Health Aging 2012

8. Association with cognitive impairment in older people?Clinical trials of n-3 PUFA • No significant benefits of n-3 PUFA supplementation on cognitive function in older people with dementia or relatively cognitive preservation • May have more demonstrable effects on cognition in older people with ‘age-related cognitive decline’, MCI or dementia but very mild cognitive dysfunction Freund-Levi et al. Arch Neurology 2006 Chiu et al. Progress in Neuropsychopharmacol biol Psychiatry 2008 Yurko-Mauro et al. Alzheimers Dement 2010 Sinn et al. Br J Nutrion 2012 Shinto et al., J Alzheimers Dis 2014

9. Guidelines for claims on cognitive function • Health claims should only be permitted when the food or food constituent is shown to have a beneficial physiologic effect -- Maintenance or improvement of a psychological, perceptual, psychomotor, or physiological regulatory function; or a reduction in a disease risk factor. • The studies must have been well designed and executed and carried out in an appropriate population, and that outcome measures utilize established and validated diagnostic tools and neuropsychological function. -- Supporting studies in well characterized subjects with mild cognitive decline, with extrapolation to more cognitively impaired patients.

10. Design of nutritional intervention trials targeting cognitive decline • Complicated by the multiple and poorly understood pathways through which nutrition affecting cognition, the multiple domains of cognition affected, individual difference of coping the pathology. • Heterogenous manifestations of cognitive decline and the wide spectrum of underlying pathyphysiological mechanisms—multidomain intervention recommended.

11. Target population • The recruitment of pre-frail and frail older persons with cognitive impairment (CDR=0.5) • Individual with MCI • PET amyloid positive individual represent approximately 20-30% of older adults aged over 70 years • Other biomarkers used to select appropriate subjects. • APOE4 positive (?) • Other populations at high risk of cognitive decline, for example those with family history of AD

12. Other recommendation • Sample size: large sample sizes are likely to be needed given the heterogeneity of the decline observed across older persons. • Length of the trial: • Symptomatic trial must be between 6 and 12 months in duration in order to observe a decline in the placebo group. • Preventive trials may require 3 to 5 years of follow-up --- may be unrealistic, individual with high risk group is more efficient and economical.

13. Endpoints/outcomes • Since multidomain intervention may be necessary, multiple outcome measures may also be needed; • Some domains (such as memory) may be considered as more clinically relevant. Batteries of test covering multiple cognitive domains; Subjective memory complaints? • Biomarkers (both CSF and imaging) • The modification of a risk factor for a disease. • Tests should be sensitive to changes • Test validated for the purpose in the specific group. • Correction for multiple test • Assess covariates, including nutritional status, physical exercise, and cognitive activity.

14. Thank you for your attention. Welcome your comments and