AT AAIC 2017

LONDON (FRONTLINE MEDICAL NEWS) – As many as a third of dementia cases could be prevented worldwide if society could adopt a life course–focused approach of supporting brain health with mostly common-sense measures.

Improving childhood education, controlling blood pressure and cholesterol, keeping socially and intellectually active, exercising, and ceasing tobacco use are among the recommendations to reduce the incidence of dementia made by a worldwide panel of expert clinicians and researchers.

The findings are part of an exhaustive report commission by The Lancet and released at the Alzheimer’s Association International Conference. The report has concluded that nine lifestyle factors, most of which are modifiable from childhood though middle age, account for 35% of dementia that strikes elderly persons, Gillian Livingston, MD , said at the conference. The report was simultaneously published .

Together, these factors, which also impact many other areas of health and well-being, dwarf the genetic risk conferred by the high-risk ApoE4 allele, said Dr. Livingston, a geriatric psychiatrist at University College London and the paper’s lead author.

Being homozygous for the ApoE4 allele confers about an immutable 7% increased chance of developing Alzheimer’s disease. But two of the other factors identified in the Lancet report, low education in childhood and hearing loss at middle age, confer even higher individual risks of 8% and 9%. And when combined with other mid-life risks of hypertension and obesity, and late-life risks imposed by smoking, depression, inactivity, social isolation, and diabetes, these factors not only dwarf the potential impact of ApoE4, but offer a lifelong chance to forestall or even prevent dementia.

The findings, all gathered from an exhaustive literature review, bolster the notion that public health interventions could block the tsunami of dementia cases that threaten to overwhelm the world’s health care resources by 2050, Dr. Livingston said.

“While public health interventions won’t prevent or cure all potentially modifiable dementia, intervention for cardiovascular risk factors, mental health, and hearing may push back the onset in many people for years. Even if only some of this promise is realized, it could make a huge difference. We have, in fact, already seen that in some populations dementia is being delayed for years. If we could achieve an overall delay of onset by 5 years, we could cut the global prevalence by half.”

The Lancet commissioned the panel of global dementia experts to review the extant literature and construct a lifespan-focused risk model. In addition to examining risk and making recommendations to ameliorate it, the panel issued recommendations about treating cognition and psychiatric and behavioral problems; protecting dementia patients in both home and long-term care settings; supporting the family members who provide most of the care for dementia patients; and helping patients and families navigate end-of-life situations.

The literature review identified nine modifiable risk factors that account for 35% of dementia risk worldwide:

• Education in youth. Less education in childhood, which the commission identified as a lack of secondary schooling, increased the risk of dementia by 8%. Improving education at this age would remove this portion of the population attributable risk factor (PAF), Dr. Livingston said.

This finding represents an enormous opportunity for improvement: The decline in dementia incidence seen in some populations occurs mostly among the better-educated. “The mechanism of prevention here appears to be increasing brain resilience,” said Lon Schneider, MD, a member of the Lancet panel.

Tackling poor childhood education is a daunting task and requires commitment from both public and private sectors, the report noted, but its importance cannot be overstated.

• Hearing loss at mid-life. This emerged as the most powerful risk factor in the analysis, conferring an independent 9% increased risk of dementia, “a relatively new idea that has not been included in previous calculations of population attributable factors,” the commission wrote. The mechanism of increased risk isn’t clear, but may be a combination of neurodegeneration and social isolation imposed by being shut out of easy communication. It’s unclear whether hearing aids can mitigate the effects of hearing loss on dementia risk, the report noted.

• Hypertension, obesity, and diabetes. Respectively, these accounted for 2%, 1%, and 1% of the PAF. Obesity is linked to prediabetes and diabetes, which are in turn linked to insulin resistance, decreased brain amyloid clearance, high blood glucose, and inflammation – all risks for Alzheimer’s disease.

The report recommends that anyone aged 45-65 years who has hypertension should be actively treated for the disorder.

• Smoking. At 5%, smoking posted the third-highest PAF. The risk is probably mediated through smoking’s detrimental effects on cardiovascular health. But the report noted that tobacco smoke contains known neurotoxins as well.

Preventing the smoking/dementia connection is simple, Dr. Livingston said. “Simply stop smoking. If you’re smoking, just stop. Please.”

• Depression. Depression in late life imposed a 4% PAF. The evidence reviewed suggested that depression is not, in fact, linked to dementia when experienced at mid-life. But late-life depression may be a prodromal symptom of dementia and biologically linked to increased stress hormones, decreased neuronal growth factors, and decreased hippocampal volume. The commission noted animal models that suggest some antidepressants, including citalopram, decrease amyloid progression.

• Social isolation. Associated with a 2% PAF, social isolation may, like depression, be a prodromal symptom. But, the report said, there is growing evidence that it actually is an independent risk factor as well. It has been shown to also increase the risk of hypertension, cardiovascular disease, and depression, all dementia risk factors in their own right.

Longitudinal studies suggest that social activities and personal connections may prevent or delay dementia, although top-grade evidence is lacking. Still, maintaining a rich social network not only reduces the chance of isolation, but helps prevent depression as well.

• Physical inactivity. Sedentary lifestyle carried a 3% PAF for dementia. Older adults who maintain physical activity are more likely to remain cognitively intact. Physical exercise improves mood, reduces the risk of falls, and maintains normal physical function. The report cited a meta-analysis of 16 studies and almost 164,000 participants without dementia; it concluded that those in the highest level of activity had a 25% decreased risk of all-cause dementia and a 45% decreased risk of Alzheimer’s disease.

The strongest evidence for exercise’s benefit on cognition may be from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Patients with a high risk of dementia who completed the lifestyle modification program of healthy diet cognitive training, vascular risk factor management, and aerobic exercise showed a slowing of cognitive decline and improvements in executive function and processing speed.

Becoming aware of the risk factors is one thing, the report said. Doing something about them is another. In general, the first step is to “be ambitious” about prevention.

“Prevention is always better than treatment,” Dr. Livingston said in an interview. “We need to start thinking about dementia not as something that simply happens outside our control, but as something that we can have an effect on.”

The Lancet commissioned the report. Dr. Livingston did not have any financial declarations but many of the other authors reported multiple relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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