The Alzheimer’s disease puzzle Part 1: An unsolved disease
Updated: Jan 9, 2020
Watching a loved one’s gradual decline from Alzheimer’s Disease is no easy feat. My family experienced this first hand as we watched my beautiful Nan - Dorothy - live with this torturous disease for years before she peacefully passed. Along with memory loss, people with Alzheimer's Disease (AD) dementia can be unpredictable, aggressive and completely different to the person they have been their whole lives. The combination of personality changes and the inability to complete everyday tasks can be an awful experience for the person living with AD and places an incredible burden on families and carers who tirelessly try to do all they can to ensure comfort and wellbeing for their loved one.
AD dementia is characterized by memory loss, confusion, changes in personality, disorientation of time and place, misplacing things, and social withdrawal. It can be challenging to recognise these behaviours as features of AD as we so often dismiss them as normal parts of aging. Dementia is currently the second leading cause of death in Australia, with AD being the most common type of dementia.Survival after a diagnosis of AD is typically between 4-8 years in those 65-years or older. Sadly, research from the U.S. shows that among 70-year-olds with AD, 61% are expected to die before age 80, compared to 30% in the general population.
Treatment of Alzheimer’s disease
While Alzheimer’s disease drugs are available, these medications are not able to stop or reverse the progression of the disease. Such medications fall mostly into one of two categories; acetylcholinesterase inhibitors or N-methyl D-aspartate antagonists (glutamate blockers). For some, medications may be modestly effective in slowing cognitive decline and reducing problem behaviours. However, research suggests this to be true for only around half of people who are prescribed these medications. On top of this, these drugs are commonly accompanied with an array of nasty side effects including nausea, vomiting and diarrhoea.
Why are current treatments not working?
Two main disease processes in the brain define AD, (1) a build-up of beta amyloid plaques and (2) neurofibrillary tangles of tau protein. The ‘amyloid hypothesis’ suggests that AD is primarily caused by the former, with the plaques being the main driver of the disease. This build-up is believed to result from an imbalance of beta amyloid production and inadequate clearance from the brain, in turn leading to neurofibrillary tangles and disease progression. Hence, treatments so far have focused on targeting the build-up of amyloid. Unfortunately, such treatments have been ineffective, suggesting that perhaps they may either be targeting the disease too late, or that maybe the amyloid hypothesis is not capturing the whole picture. Other noted concerns with the amyloid hypothesis include the presence of amyloid plaques in cognitively intact individuals (if people without AD also have these plaques then how can this be the sole driver of AD?)and the weak correlation between number or density of amyloid plaques and cognitive decline (how come greater density of plaques does not mean greater cognitive decline?). Also, since the brain pathology starts well before the onset of symptoms (and diagnosis), treatment may simply be too late.
Lack of success with pharmacological treatments has prompted a change in focus towards lifestyle factors and health behaviours. Current prevention recommendations for AD include regular exercise and social engagement, reducing smoking and management of hypertension, depression, diabetes and obesity. Interestingly, there is strong overlap between risk factors for cardiovascular disease and dementia. What is good for your heart is good for your brain. Hence, dietary recommendations for cardiovascular disease such as a Mediterranean-style diet may also hold value for AD prevention. Identifying diet and other lifestyle factors as potential contributors to AD highlights the gut microbiome as a potential piece in this large and complex AD puzzle…
Stay tuned for Part 2: Clues from the Microbiome.
Madeline West is an Associate Nutritionist and research assistant currently working with Dr Amy Loughman at the Food & Mood Centre on the Healthy Brain Project (Microbiome substudy). This post was originally published on the Food & Mood Centre website.