Diseases of Aging

Learning Objectives: Describe symptoms and etiology/ progression of Alzheimers and Parkinsons Disease List plants that are used in prevention and treatment of Alzheimers and Parkinsons and describe their activities.

Aging population

Percentage of population:

Baby Boomers (1946 1964)

Year 1975 2000 2015 2030

% 65+ 10.5 12.6 14.7 20.0

% 80+ 2.1 3.3 3.8 5.3

US Census Bureau

Panax spp.
Ginsenosides
anticarcinogenic anti-inflammatory antiatherosclerotic antidiabetic antistress effects on the central nervous system (may protect neurons and modulate neurotransmitters

Dementia
Usually found in older patients US population growing older

US Census Bureau

Alzheimers Disease
= Slowly progressing dementia as nerve cells degenerate and die - Affects approx. 4.5 million Americans (doubled since 1980) - Patients live average 8 yrs after diagnosis - Usually develops after age 65 But.rare, inherited form can appear in patients 30-40 yrs 1 in 10 indiv. over age 65

1 in 2 indiv. over age 85

- Genetically / family based in 10% cases

Alzheimers Disease Symptoms:

Memory loss and confusion

Personality change
Behavior problems Indicated by: Amyloid plaques - clumps of protein accumulating outside brain nerve cells Neurofibrillary tangles - twisted protein strands formed inside cells

Normal synapse

Alzheimers -amyloid clumps block cell-cell signaling at synapses Tangles destroy transport system within nerve cells

Alzheimers Cortex shrivels affecting thinking, planning and remembering Ventricles expand

Hippocampus, involved in memory formation, shrinks

Disease Progression of Alzheimers

Learning, memory, thinking, planning

Speech center, orientation

Cell death is widespread Communication, recognition, self-care lost

www.Alz.org

Turmeric Curcuma longa

(Zingiberaceae)

Active ingredient: Cucurmin Antioxidant

Anti-amyloid

Anti-inflammatory
Anti-tumor

Alzheimers Disease
Treatment: Ginkgo biloba extracts - Evidence suggests they may inhibit formation of beta-amyloid
(protein that forms amyloid plaques)

- May improve blood circulation in brain - Antioxidant (protects neurons from damage) - Anti-inflammatory

Parkinsons Disease
The average age of onset is 60 years; (estimated 5 - 10 % under age 40).

Neurodegenerative Disease - Neurons disintegrate in basal ganglion - Dopamine is selectively depleted Effects: Difficulty initiating movements Muscle rigidity Tremors Anxiety & depression Loss of voice volume, speed, clarity Memory loss

Parkinsons
Loss of neurons in substantia nigra
Imbalance in Dopamine/ Acetylcholine Neurotransmitters

Parkinsons Disease Treatment:

Enhancement of dopamine levels Problem: Dopamine is not readily transported across blood-brain barrier
Blood Dopamine

L-dopa

Rxn catalyzed by enzyme: Aromatic-L-amino-acid decarboxylase

Brain

Dopamine

Solution: Immediate precursor, L-dopa, does!

3,4-dihydroxy-L-phenylalanine

L-dopa - Obtained in 1913 from Broad Bean Vicia faba (Fabaceae) Ingestion produces substantial increase in L-DOPA plasma levels & improved motor performance

Potential Parkinsons Treatment Marijuana - Cannabis sativa THC - tetrahydrocannabinol

- Conflicting evidence of its potential for PD treatment - Antagonists may offer the most benefit
Produced in trichomes;
(Mahlberg & Kim, 2005)

THC - tetrahydrocannabinol
Cannabinoid chemical receptors: CB1 - brain CB2 - peripheral immune system Endogenous cannabinoids (anandamide) * Roles in: regulation of motor behavior cognition learning and memory reduced pain perception neuronal development

Complex interactions between CB and dopamine transmission

 CB1 receptors abundant in the basal ganglia and the cerebellum, areas that control movement
Decrease with age Increased in patients with Parkinsons Disease (PD)

CB1 receptor binding altered in the basal ganglia of humans affected by several neurological diseases
Overactive in people with PD

Cannabinoids (synthetic, plant-derived, & endogenous) strongly affect motor activity (mostly inhibitory)
(reviewed in Romero et al. 2002)

Cannabinoids
May reduce L-Dopa induced dyskinesia in Parkinson's disease Dyskinesia: distortion or impairment of voluntary movement (spasm, tic)
Antagonists may be useful in treatment of PD (since CB receptors are overexpressed

Life expectancy is increasing:

Year 2008 2000 1990 1980 1970 1960 1950 1940 1930 1920 1910 Both 78.0 76.8 75.4 73.7 70.8 69.7 68.2 62.9 59.7 54.1 50.0 Male 75.5 74.1 71.8 70.0 67.1 66.6 65.6 60.8 58.1 53.6 48.4 Female 80.5 79.3 78.8 77.4 74.7 73.1 71.1 65.2 61.6 54.6 51.8

1900

47.3

46.3

48.3

National Vital Statistics Report, 2004 and U. S. Census Bureau, 2012