Nutrition and Water for Dementia Prevention

Transcription

1 台日生技醫藥研討會 - 自然療法於失智症預防及照護之應用 Nutrition and Water for Dementia Prevention 胡朝榮 Chaur-Jong Hu, M.D. Professor and Direction, Department of Neurology and Dementia Center, Shuang Ho Hospital, Taipei Medical University

2 The age-adjusted prevalence of all-cause dementia was 8.04%. It increased by double every 5 years of age. A Nationwide Survey of Mild Cognitive Impairment and Dementia, Including Very Mild Dementia, in Taiwan PLOS ONE, June 2014, Volume 9, Issue 6, e100303

3 Number of people with Alzheimer's disease is expected to triple in 2050 L.E Hebert et al, Neurology 2013

4 Dementia increases the cost of health care NEJM 2011, 365: 1069

5 World Alzheimer Report 2009

6 Introduction Epidemiology of Dementia Others 15.7% 23.2% 7.4% 53.7% Vascular Dementia Mixed type Alzheimer Disease Acta Neurol Taiwan : J Neurol Sci :67-75

7 Alzheimer s Disease (AD) Dr. Alzheimer reported the case in Nov, (about 100 years ago) Clinical aspects of AD A: daily Activities impairment B: Behavior-psychiatry symptoms Auguste D. The original AD patient. Auguste D. went to the clinic of Dr. Alzheimer on Nov, 25, 1890 and died on Apr, 8, PS1 mutation?, Lancet Neurol Feb;12(2): C: Cognition impairment C: Care-giver burden

8 Pathology of AD Neuritic plaques Neurofibrillary tangle

9 revising the NINCDS ADRDA criteria Probable AD: A plus one or more supportive features B, C, D, or E A. Presence of an early and significant episodic memory impairment B. Presence of medial temporal lobe atrophy C. Abnormal cerebrospinal fluid biomarker (Amyloid decreased, Tau increased) D. Specific pattern on functional neuroimaging with PET E. Proven AD autosomal dominant mutation within the immediate family (Mutation on APP or PS1 or PS2 genes) Lancet Neurology 6:734, 2007

10 Figure. T1-weighted MR coronal images orientated perpendicular to the long axis of the hippocampus (slice thickness, 5 mm) and showing medial temporal lobe atrophy (MTA) rating scores. Barber R et al. Neurology 1999;52: by Lippincott Williams & Wilkins

11 PIB and AV-45 are tracers for amyloid PET AD Normal Alzheimer Disease Neuroimage Initiative-2 TMU-SHH &CGMH

12 revising the NINCDS ADRDA criteria Criteria for definite AD Both clinical and histopathological (brain biopsy or autopsy) evidence of the disease, as required by the NIA-Reagan criteria for the post-mortem diagnosis of AD; criteria must both be present Both clinical and genetic evidence (mutation on chromosome 1, 14, or 21) of AD; criteria must both be present Lancet Neurology 6:734, 2007

13 Lancet Neurology, 2010, 9:119

14 Approved Therapies for AD ChEIs for mild to moderate AD Donepezil Galantamine Rivastigmine NMDA* antagonist for moderate to severe AD Memantine *N-methyl-D-aspartate. See SmPC for each product.

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16 Risk factors of Dementia Alzheimers Dement Jun;11(6):

17 viewarticle/867868_slide

18 Nutrition and prevention of Alzheimer s dementia Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. Front Aging Neurosci. 2014; 6: 282.

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20 Study intervention Selegiline 10 mg qd; vitamin E 2000 IU qd Vitamin E 2000 IU qd; memantine 20 mg qd Subjects Main findings Important secondary outcomes Moderate AD, n= 341. Mild to moderate AD, n= 613. No difference between groups for progression of disease, institutionalization, or death. ADCS-ADL scores decline 3.15 less in vitamin E group than placebo representing a 19% slowing in rate of decline. No effect of memantine. Analyses adjusted for entry MMSE scores showed delay to endpoints for selegilene (median 655 days, p = 0.012) or vitamin E (median 670 days, p < 0.001). None. 800 IU vitamin E and 500 mg vitamin C and 900 mg α-lipoic acid; 1200 mg coenzyme Q qd Mild to moderate AD, n= 78. Cerebrospinal fluid F2- isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. None.

21 Latrepirdine 5 or 20 mg qd vs. placebo (CONCERT-on donepezil) and CONNECTION Mild to moderate AD, CONCERT, n = 1050; CONNECTION, n = 598. No effect on ADAS-Cog outcome measures. None. 900 mg qd of DHA Normal cognition with memory complaints, n = 485. Less PAL six pattern errors with DHA vs. placebo (difference score, ± 0.76 [-3.1, -0.14, 95% CI], p = 0.03). Improved immediate and delayed Verbal Recognition Memory scores (p < 0.02). 1.7 g DHA and 0.6 g eicosapentaenoi c acid vs. placebo Mild to moderate AD, n= 204. No effect on primary outcome measures of MMSE and ADAS-Cog. Subjects with mild AD, (MMSE > 27 points), showed a significant (p < 0.05) reduction in MMSE decline rate. DHA 2 g qd vs. placebo Mild to moderate AD, n= 402. No effect on primary outcome measures of ADAS-Cog and CDR sum of boxes. Reduced rate of decline on ADAS-Cog, MMSE, but not CDR sum of boxes for those lacking an ApoE 4 allele.

22 Folic acid 0.8 mg, vitamin B mg and vitamin B6 20 mg vs. placebo Mild cognitive impairment, n = 168. Rate of cerebral atrophy was 3-fold lower in treated vs. placebo group (p < 0.001). The effect was more pronounced for those with homocysteine > 13 mmol/l. Folate 5 mg, vitamin B6 25 mg, vitamin B12 1 mg qd vs. placebo Mild to moderate AD, n= 409 Treatment was effective in reducing homocysteine levels (p < 0.001), but had no effect on rate of change in ADAS-cog score. None. Subjects received one of two isocaloric conditions (690 calories) in a randomized order: emulsified MCTs, or emulsified long chain triglycerides as a placebo AD (n = 15) or mild cognitive impairment (n = 5). No effect on primary outcome measures for the composite groups. In the 4-group, there was a significant improvement in ADAScog scores following MCT treatment (F[1,7] = 6.36, p = 0.04). Subjects whose β-ohb levels were higher showed improved paragraph recall with MCT administration (r = 0.50, p = 0.02).

23 Oral ketogenic compound, AC vs. placebo Mild to moderate AD, n= 152 ADAS-Cog score on Day 45: 1.9 point difference, p = in ITT favoring treatment. 4(-) participants (n = 55) administered AC-1202 had a significant 4.77 point difference in mean change from Baseline in ADAS-Cog scores at Day 45 (p = ). Combination supplement with DHA, uridine, choline [Souvenaid ] Mild AD, MMSE 20-26, n= 225 A significant treatment effect (F[1,319] = 4.0, p = 0.046) was shown in patients with ``high'' baseline ADAS-cog, but not in patients with ``low'' baseline ADAS-cog (F[1,250] = 1.25, p = 0.265). Overall, intake adherence was significantly correlated with ADAS-cog improvement in the active product group (correlation coefficient = ; p = 0.019), but not the control group. Combination supplement with DHA, uridine, choline [Souvenaid ] Mild to moderate AD, n= 527. No significant difference in ADAS-cog between study groups [difference = 0.37 points, (standard error) SE = 0.57, p = 0.513). None.

24 Huperzine A (200 mg BID [n = 70] or 400 mg BID [n = 70]) vs. placebo Mild to moderate AD, n= 210. No significant difference in change in ADAS-cog scores for Huperazine 200 mg BID ( ± vs ± 5.17, p = 0.98). Huperzine A 400 mg BID treatment effects on ADAS-Cog change demonstrated a nonsignificant trend 1.92 ± 5.30 point improvement (p = 0.07 for the LOCF ANCOVA). Ginkgo Biloba 120 mg BID vs. placebo Normal adults (n= 2587) and MCI (n = 482). Hazard ratio for G. biloba vs. placebo for incidence of dementia was 1.12 (95% confidence interval [CI], ; p = 0.21) and for AD, 1.16 (95% CI, ; p = 0.11). Rates of change over time in 3MSE, ADAS-Cog, and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions did not differ between groups. Only few nutritional supplements confer beneficial effects on AD progression, mainly for the milder cases.

25 Curcumin ( 薑黃素 ) Curcumin is a bright yellow chemical produced by some plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family (Zingiberaceae). It is sold as an herbal supplement, cosmetics ingredient, food flavoring, and food coloring. Turmeric plant Turmeric

26 Different mechanisms of action of curcumin in AD Ann Indian Acad Neurol. 2008; 11:

27 Curcuminoid Sci Rep Jul 13;6:29760.

28 plasmon-activated water

29 Transgenic AD (APP/PS1) mouse model for investigating the effect of PAW Wild type 5 M APP/SP1 5 M PAW regular water PAW regular water Memory test (NOR) Pathology (amyloid/tau) 29

30 Memory test: Novel Object Recognition (NOR) * p=0.003 * p= Novel object recongnition % WT WT-PAW AD AD-PAW WT=wild type, WT-PAW=wild type with PAW, AD=Alzheimer s disease, AD-PAW=AD with PAW 30

31 (1) (2) AD AD+PAW (1) Senile plaques (amyloid) (2) p- Tau in in wild type (Untreated) and AD mice (3) total Tau and p-tau on cortex and hippocampus in wild type (WT) and AD mice, 14-monthold with/without PAW for 9 month (3) 31

32 Thank you for your attention Chaur-Jong Hu, M.D. Professor and Direction, Department of Neurology and Dementia Center, Shuang Ho Hospital, Taipei Medical University