Mona Osman MD, MPH, MBA

Background Burden of DiseaseWhat is Dementia? Can we prevent Dementia?

The improved health care system and aging of the population, led to an increase in the prevalence of Non-Communicable Diseases including Dementia

Dementia is a major cause of disability and dependency among older people worldwide and can lead to institutionalization and poor quality of life

It is overwhelming to the affected individuals and to their families & caregivers with negative impact at the physical, psychological and economical levels

Stigmatization is significant as a result of lack of awareness regarding the disease in most of the countries

World Health Organization considers Dementia as a public health concern that should be addressed systematically in all countries.

Dementia: a public health priority; WHO (2012)

The total number of people with dementia worldwide in 2010 is estimated at 35.6 million

It is projected to nearly double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050

The total number of new cases of dementia each year worldwide is nearly 7.7 million, implying one new case every four seconds

The total estimated worldwide costs of dementia were US$ 604 billion in 2010

Dementia: a public health priority; WHO (2012)

Dementia is NOT a normal part of aging It is a syndrome, usually of a chronic or progressive

nature, caused by a variety of brain illnesses that affect memory, thinking, behaviour and ability to perform everyday activities + decline from previous level of function severe enough to interfere with daily function and

independence Alzheimer’s disease is the most common form of

dementia (60–70% of cases) Other major contributors include vascular dementia,

dementia with Lewy bodies, and frontotemporaldementia.

Dementia: a public health priority; WHO (2012)

Dementia affects mainly individuals older than 65 years. It rarely occurs before that age ( 2-9% of the cases)

Risk Factors: Non-Modifiable Risk Factors Age Family history of dementia Apolipoprotein E4 genotype: can increase risk of

dementia 2 to 10 fold Modifiable risk factors: cardiovascular risk factors

and co-morbidities Others: lower educational (Having a college education will delay

onset by 2 years)

The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for dementia in older adults ( I recommendation)

BUT, cognitive function should be assessed if cognitive impairment or deterioration is suspected

Evidence from the history and mental status examination that indicates major impairment in learning and memory as well as at least one of the following: Impairment in handling complex tasks Impairment in reasoning ability Impaired spatial ability and orientation Impaired language

The cognitive symptoms must significantly interfere with the individual's work performance, usual social activities, or relationships with other people

This must represent a significant decline from a previous level of functioning

The disturbances are of insidious onset and are progressive, based on evidence from the history or serial mental-status examinations

The disturbances are not occurring exclusively during the course of delirium, they are not better accounted for by a major psychiatric diagnosis and they are not better accounted for by a systemic disease or another brain disease

Role of: Dietary Supplements Diet Lifestyle & Activity Medications

It is an herb used by many older adults for cognitive health Theory: improved brain function through cerebral vasodilation, a

reduction in blood viscosity, a reduction of oxygen free radicals. Evidence: Gingko Evaluation of Memory (GEM) study

To determine whether ginkgo biloba supplementation can prevent dementia among older adults who were cognitively intact or had mild cognitive impairment (MCI) at baseline

3069 participants randomized into gingko biloba treatment and placebo treatment groups

Follow up for a median of 6.1 years Result: no difference in dementia incidence in all participants or in the rate of

progression to dementia in participants with MCI between the two groups Safety:

possible interaction with antiplatelet or anticoagulant medications with possibility of bleeding

Interaction with medications metabolized in the CYP2C19 pathway, such as omeprazole, valproic acid and phenytoin through induction of the enzyme

Dekosky ST, Williamson JD, Fitzpatrick AL et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 300(19), 2253–2262 (2008).

Theory: enhanced homocysteine metabolism through vitamin B supplementation may have a beneficial effect on reducing the risk of dementia

Evidence: In a randomized controlled trial (1) , vitamin B supplementation (400

µg B12, 25 mg B6, 2 mg folic acid) did not result in better cognition over a period of 24 months compared with placebo among cognitively intact older men aged 75 years and older. At 8 years follow-up, there was a non-significant decrease in the risk of cognitive impairment and dementia

In another randomized controlled trial (2) of cognitively intact older adults with elevated homocysteine levels, supplementation with B vitamins (500 µg B12, 10 mg B6, 1000 µg folate) for 2 years lowered homocysteine levels, but did not demonstrate any improvement in cognitive performance compared with placebo.

1. Ford AH, Flicker L, Alfonso H et al. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology 75(17), 1540–1547 (2010).2. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N. Engl. J. Med. 354(26), 2764–2772 (2006).

Theory: oxidative stress is hypothesized to contribute to the development of dementia, antioxidants such as vitamin E may be effective.

Evidence: Women's Health Study (randomized placebo-controlled) – compared vitamin E supplementation (600 IU every other day) to placebo in women aged 65 years or older. Participants' cognitive performance were followed at 2-year intervals for a mean of 9.6 years using standardized tests. There was no difference in cognitive performance between the vitamin E-treated group and placebo group (1).

Safety: vitamin E supplementation in doses higher than 400 IU daily was found to be harmful as well as long term intake of 400 IU of Vitamin E was found to result in higher rates of heart failure and hospitalizations for heart failure (2).

1. Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch. Intern. Med. 166(22), 2462–2468 (2006).2.Lonn E, Bosch J, Yusuf S et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293(11), 1338–1347 (2005).

Group of polyunsaturated Fatty acids Theory: through reduction in CVD and stroke, reduction in

the synthesis of pro-inflammatory cytokines Evidence: observational studies suggested that Omega-3

Fatty Acids and high fish intake may have a protective effect on cognition in cognitively intact adults. But, this has not been demonstrated consistently.

A large prospective cohort study of elderly men in the Veterans Affairs Normative Aging Study did not find any association between Omega 3 Fatty Acids intake and better cognitive function or less cognitive decline in over 6 years of follow-up

Van De Rest O, Spiro A, Krall-Kaye E, Geleijnse JM, De Groot LCPGM, Tucker KL. Intakes of (n-3) fatty acids and fatty fish are not associated with cognitive performance and 6-year cognitive change in men participating in the Veterans Affairs Normative Aging Study. J. Nutr. 139(12), 2329–2336 (2009).

Theory: Through the anti-oxidant effect Evidence:

inconsistent for the protective effects of vitamins A and C against cognitive decline and impairment or dementia.

insufficient to recommend vitamin A or supplementation for cognitive health.

Toxicity: Increased risk of lung cancer in smokers with high

doses of carotenoids Chronic use of vitamin A (15 mg per day or more in

adults for months) may cause toxicity resulting in hypercalcemia, bone demineralization and pain.

Vitamin C may cause hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency

Theory: In the brain, vitamin D binds to vitamin D receptors which have been identified in the human cortex and hippocampus, which are key areas for cognition.

Evidence: there are no available randomized control trials of vitamin D supplementation for the enhancement of cognition or prevention of cognitive decline and dementia.

Conflicting Evidence: High dietary intake of fish and omega-3 fatty acids may decrease the risk of cognitive impairment, while cholesterol and fatty acid intake may increase the risk.

Large longitudinal studies have shown a benefit for higher fish consumption on the risk of dementia and cognitive decline.

A diet high in fruits and vegetables may decrease the risk of cognitive decline, but data is less clear.

Higher levels of physical and mental activity (memory training, use of external memory cues) as well as social interaction may help maintain cognitive function during aging.

One study randomly assigned 170 older adults (> 49 years) to an education/usual care and to a 24-week home-based physical activity program . After 18 months, analysis of cognition in the 138 participants who completed the program demonstrated a modest benefit for the physical activity intervention (1).

one of three cognitive interventions or a control group, and found that a 10-week training program in inductive resulted in improved performance on the Instrumental Activities of Daily Living that was sustained at five years (2).

1. lautenschlager, NT, Cox Kl, Flicker L, et al. Effect of physical activity on cognitive function in older adults at risk of Alzheimer disease: a randomized trial. JAMA 2008; 200: 10272. Willis SL et al. Long term effects of cognitive training on everyday functional outcomes in older adults. JAMA 2006; 296: 2805

Hypertension appears to be associated with an increased risk of both vascular dementia and Alzheimer disease (AD), but the effect of antihypertensive treatment on reducing risk is uncertain.

Randomized, controlled studies have yielded conflicting data regarding the effect of antihypertensive therapy on dementia prevention

Some epidemiologic studies, have suggested that NSAID protect against the development of cognitive decline.

However, their use is not currently supported by randomized clinical trials.

Retrospective studies have suggested that statinsmay prevent the development of dementia through: A direct association between amyloid processing and

cholesterol in the brain An indirect effect via decreasing the risk of stroke

Prospective observational studies yielded somewhat mixed results regarding the efficacy of current or past statin use in reducing the incidence of dementia.

Some studies suggested that statins may cause cognitive dysfunction in selected patients.

Epidemiologic studies suggested that estrogen replacement therapy might prevent dementia.

YET, data from the Women's Health Initiative (WHI) and the WHI Memory Study (WHIMS) did not support this.

None of conducted studies could prove a causal effect between assessed factors and incidence of Dementia.

Much of the interventional research done has been inconclusive, contradictory, and mainly from observational studies. Very few randomized controlled trials were conducted.

Current evidence is insufficient to support the association of any modifiable factor, pharmacologic agent, or dietary supplement with a reduction in the risk of Dementia ( namely Alzheimer Disease)A consensus statement from the National Institutes of Health's State-of-the-Science Conference on Preventing Alzheimer's Disease and Cognitive Decline

Some promising data: Benefit of physical activity Social engagement Early recognition and treatment of depression

Need to conduct more randomized controlled studies to determine ways and possibility of prevention.

No real evidence regarding prevention of dementia!

There is no effective prescription medication to prevent cognitive decline in healthy older adults.

Primary prevention should focus on improving risk factors for vascular diseases, including diabetes, hypertension, obesity, smoking, and physical inactivity.