Alzheimer’s Disease

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Alzheimer’s Disease: Prevention is the Best Treatment

Siddharth Sehgal, MD

Alzheimer’s disease (AD) is a progressive neurodegenerative condition and the most common cause of dementia. It accounts for about 60-80 % of all cases of dementia1. There are currently no curative or prevention therapies available for the disease. Medications prescribed for Alzheimer’s disease (AD) symptoms can temporarily help individuals with thinking, memory, or speaking skills and can help with some of the behavioral and personality changes associated with AD.  everal lines of evidence indicate that lifestyle habits and genetic factors play an important role in determining a person’s risk of developing AD2.

There have been a few recent disappointments with AD therapies when Biogen and Esai released negative results from a promising drug trial (3) and then Novartis, Amgen and Banner Alzheimer’s Institute announced in July their decision to not pursue further studies with a potential AD drug4. But new research presented at the Alzheimer’s Association International conference held in July at Los Angeles has provided evidence of a potential preventive strategy. Results from this study indicate that certain healthy lifestyle habits can reduce the risk of developing AD and even overcome the genetic risk in some susceptible individuals5.

During this retrospective cohort study,196 383 individuals aged at least 60 years, without evidence of cognitive impairment or dementia at baseline were followed for a median of 8 years. Risk assessment was performed using lifestyle and genetic risk scores. Lifestyle risk score was determined by a combination of smoking status, alcohol consumption, physical activity, and dietary habits. During the follow up period, a total of 1769 patients were diagnosed with new onset dementia. The incidence of dementia was noted in 1.23% of the high genetic risk group as compared to 0.63% in the low genetic risk cohort. The genetic risk was seen to be independent of the lifestyle factors.

About 68% participants followed a favorable lifestyle and 8% were noted to have an unfavorable lifestyle.

Dementia risk was seen to increase with worsening of lifestyle scores in a linear fashion. In the unfavorable lifestyle group, 1.16% persons developed dementia while 0.82% in the healthy lifestyle were diagnosed. Favorable lifestyle was associated with a lower risk of dementia despite an unfavorable genetic risk profile.

Favorable lifestyle habits in this study included: no smoking, limiting alcohol consumption to moderate levels, regular physical activity and maintaining a healthy diet. Regular physical activity was defined as per the American Heart Association (AHA) guidelines: 150 minutes of moderate or 75 minutes of vigorous activity per week (or an equivalent combination). This level of exercise, along with a healthy lifestyle, has also been associated with lowered risk of stroke and cardiovascular disease. Moderate alcohol consumption was defined according to the US dietary guidelines: 14g/day or less for women and 28g/day or less for men. Healthy diet was based on the dietary recommendations for maintaining optimal cardiometabolic health: this included regular consumption of at least 4 of the 7 food groups which constitute a healthy diet6.

This study provides evidence to support the benefits of a healthy lifestyle in reducing risk of dementia, even in individuals who may be at a higher genetic risk of developing dementia, including AD.  These results reinforce the American Heart Association’s healthy lifestyle recommendations for a healthy heart and healthy brain.

 

References:

  1. https://www.alz.org/alzheimers-dementia/what-is-dementia
  2. MangialascheF,KivipeltoM,SolomonA, Fratiglioni L. Dementia prevention: current epidemiological evidence and future perspective. Alzheimers Res Ther. 2012;4(1)
  3. http://investors.biogen.com/news-releases/news-release-details/biogen-and-eisai-discontinue-phase-3-engage-and-emerge-trials
  4. https://www.novartis.com/stories/discovery/stopping-alzheimers-disease-it-starts
  5. Ilianna Lourida, PhD1,2; Eilis Hannon, PhD1; Thomas J. Littlejohns, PhD3; et al. Association of Lifestyle and Genetic Risk With Incidence of Dementia. JAMA. Published online, July 13, 2019.
  6. Dietaryandpolicyprioritiesfor cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation. 2016;133(2): 187-225
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Clinical Trials on VCID in Alzheimer’s Disease

Reem Waziry, MD, MPH, PhD

This year at ISC19, Dr. Eliezer Masliah MD highlighted key ongoing trials on vascular cognitive impairment and dementia (VCID) in Alzheimer’s disease (AD)1. Currently, there are 140 AD trials at different stages of development covering a wide array of topics that include pharmacological, neuropsychiatric or caregiver interventions. Many of the pharmacological trials target vascular interactions of AD with VCID.

Key ongoing pharmacological trials at early stages include The Calibrex in patients with cognitive impairment at risk of AD2. Another key trial targets blood pressure and vasculature in individuals with mild cognitive impairment. A third trial investigates anti-hypertensive drugs to receptive blockers. This includes a number of anti-hypertensive drugs with neurocognitive function (as the primary outcome) in individuals with already mild cognitive impairment or AD.

Non-pharmacological trials include a study from Minnesota and UC San Diego with 300 participants – these participants are individuals with mild cognitive impairment, or very prodromal stages, that investigate the impact of aerobic exercise on cognition3. There are a number of measurements of blood flow, brain atrophy and other outcomes. Other examples include a trial targeting healthy diet interventions, comparing Mediterranean intervention with or without exercise looking at well-being and global cognition.

Many of the above trials will be reporting between 2019 and 2022, bridging key gaps in clinical management and treatment of VCID and Neurocognitive disorders. For more info on ongoing trials, please refer to: https://www.ninds.nih.gov/Disorders/Clinical-Trials

 

REFERENCES:

  1. Masliah, Eliezer. Clinical Trials on VCID in Alzheimer’s Disease. NIH Clinical and Applied Research Programs in Vascular Contributions to Cognitive Impairment and Dementia (VCID) (Joint Government Agency Session) [oral presentation]. In: The International Stroke Conference of the American Heart Association; 2019 Feb 6–8; Honolulu, HI.
  2. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT01984164, CAndesartan vs LIsinopril Effects on the BrRain (CALIBREX); 2013 Nov 14 [cited 2019 March 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT01984164
  3. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 -. Identifier NCT03313895, The ACT Trial: Effects of Combined Aerobic Exercise and Cognitive Training in MCI; 2017 Oct 18 [cited 2019 March 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03313895