CHAPTER 2
Diagnosing dementia
Cognition changes as we age
As we age, our cognitive capabilities undergo natural changes. It may seem like an overall decline. However, it is essential to note that, generally, these changes are subtle and do not significantly impact our daily lives. Some aspects of our cognition may even improve with age.
The most prominent change is an overall slowing of thinking, especially relating to complex cognitive tasks. For example, studies have shown that a 20-year-old is, on average, 75% faster than a 75-year-old at a test where they have to match symbols to numbers based on a key. As we age, this change affects our problem-solving abilities, particularly in unfamiliar situations. Older people may also have difficulties multitasking, maintaining focus, and using their working memory, commonly referred to as short-term memory, for example, the ability to memorise and remember a phone number. They may have difficulties finding words quickly.
At the same time, older people typically have a more extensive vocabulary and better general knowledge. Adults in their 70s and 80s know more words than those in their 20s, 30s and 40s. Expert knowledge and skills grow with age, and our reading and verbal reasoning ability tends to remain unaffected or may even improve. Long-term memory is typically maintained as we age.
Dementia, ageing or something else?
Did you forget why you went into the bedroom? Or suddenly, can’t remember your cousin’s name when introducing them? Many of these symptoms are not a sign that you are developing dementia. Forgetting to pick something up from the shop on the way home from work or not being able to recall the name of someone on television are everyday phenomena. Some changes, such as being unable to think of a person’s name, can become more prominent with normal ageing. These “innocent” memory lapses can become much more frequent when people are under a lot of stress, giving a false impression that dementia is beginning. In this situation, the individual is so preoccupied with the cause of their stress that they struggle to pay attention to other sources of information. For instance, forgetting details of conversations or plots of movies they have recently watched because their mind was elsewhere at the time.
If you are worried about your memory or that of someone you love, see your GP to discuss your concerns.
How dementia is diagnosed
Identifying symptoms indicative of dementia, from natural ageing-related cognitive changes and/or other confounding factors in a person’s life that may be affecting their mental capabilities is difficult. Accurate diagnosis requires time and continues to challenge clinicians. It’s thought that the disease process may occur for up to 20 years before obvious signs appear. Cognitive tests and scans can be standard in the early stages when someone is showing some signs that could reflect dementia. On the other hand, some people show physiological signs of dementia, e.g. changes in gait or posture, but do not exhibit obvious symptoms.
Firm diagnoses are often made when cognitive symptoms have amplified and effect a person's everyday life. Personality changes, confusion, problems navigating familiar environments, and difficulties performing routine tasks may have surfaced, and brain scans may show advanced pathological changes, such as plaque formation and/or tissue loss.
Researchers and clinicians are working hard to develop new ways to identify the signs and symptoms of dementia to enable earlier diagnoses and interventions. They focus on three areas – cognitive testing, brain scans and biomarkers.
Cognitive testing
When signs of cognitive change become too pronounced to ignore, a GP visit is often the first step. The doctor will take a patient’s history, assess their physical and mental abilities, order further tests, and, if necessary, refer them to a specialist geriatrician, neurologist, psychiatrist, or to a specialist clinical neuropsychologist.
GPs and specialists use standardised cognitive tests to quantify a person’s mental capabilities and identify anomalies. Examples of very brief general cognitive screening tools are the Mini-Mental State Examination (MMSE) and the clock-drawing test.
Brain scans
Brain imaging alone does not provide a definitive diagnosis. It does provide valuable information that, combined with cognitive tests, helps specialists to make accurate diagnoses. Imaging technologies, such as CT (Computed Tomography) or MRI (Magnetic Resonance Imaging), visualise brain structures and allow clinicians to detect changes indicative of some dementia-causing conditions, such as tissue loss.
PiB-PET (Pittsburgh Compound B Positron Emission Tomography) can detect and quantify amyloid-beta accumulations, a key player in Alzheimer’s disease. Other types of imaging, such as fMRI (functional MRI) and SPECT (Single-photon emission computed tomography), show localised changes in brain activity and may thus reveal affected brain areas and help distinguish between dementia types.
Biomarkers
Biomarkers are measurable parameters or identifiable characteristics in the body, like specific proteins, genes, or molecules, that provide valuable information about someone’s health. Genetic tests, for example, can be used to screen a person’s DNA for the presence of gene variations that put them at higher risk of developing younger onset Alzheimer’s. Developing new biomarker tests for different types of dementia holds immense promise for allowing earlier and more accurate diagnoses.
Recently, researchers have developed blood tests designed to detect elevated levels of amyloid-beta and tau, which have proven highly effective in detecting Alzheimer’s pathology. Another recently developed biomarker test– SYNTapTM – promises to aid the diagnosis of Lewy body dementia by detecting misfolded alpha-synuclein aggregates in cerebrospinal fluid.
The benefits of early and accurate diagnosis
Diagnosing dementia as early as possible allows individuals and families to plan, access support services to live well, and potentially benefit from treatments and research opportunities. It helps rule out other potential causes of memory loss. It also allows for more informed decisions about care and living arrangements.
Accurate diagnosis is essential because dementia’s underlying diseases affect different brain areas, resulting in varied symptoms. Information about the specific disease can help you understand the changes the person with dementia is experiencing and help identify the best strategies to manage the disease and maximise their quality of life. S
After a diagnosis: the need for support
Supporting someone living with dementia involves patience, empathy, and an understanding of their changing needs. At first, people living with dementia may experience small changes in thinking, memory, and reasoning that affect their daily lives. With support, they may be able to continue working and travelling. However, eventually, they will need more help with simple everyday activities, like dressing and eating. After a disease diagnosis, it is important to keep loved ones active with hobbies and interests they enjoyed in the past. Social programs such as music and movement therapy and visits with animals can help stir memories, foster emotional connections with others, lessen anxiety and irritability, and make people feel more engaged with life.
Genetics
It’s been more than 100 years since the first description of Alzheimer’s disease in 1907. Since then, researchers have learned much about the underlying conditions that cause dementia. However, many questions remain, especially about what causes the underlying pathologies to emerge. While the immediate causes remain largely unclear, we have made advances in our understanding of the role of genetics and several other health factors in modifying the risk of developing dementia.
Several genetic factors have been found to be linked to an increased risk of dementia, most of which are associated with processes involved in protein aggregation, one of the hallmarks of many types of dementia. A family history of dementia, for example, is a risk factor for Alzheimer’s disease. Most cases of younger-onset Alzheimer’s are inherited and can be traced to mutations in one of three genes:
amyloid precursor protein (APP)
presenilin 1 (PSEN1)
presenilin 2 (PSEN2).
The presence of one or more of these mutated genes almost guarantees the development of Alzheimer’s at a relatively young age. However, even without these genes, some people still develop Alzheimer’s. A subvariant of a gene known as apolipoprotein E (ApoE), on the other hand, has been found to strongly indicate the development of late-onset Alzheimer’s disease. People with one copy of the ApoE 4 variant are about three times more likely to develop the condition, and those with two copies have an even higher risk (8-12-fold increase). In fact, ApoE 4 is so strongly linked to Alzheimer’s disease that more than half of all people with the condition have at least one copy in their genomes. Those with two developed Alzheimer’s, on average, 10 years earlier.
Still, while the presence of ApoE 4 significantly increases the likelihood of developing Alzheimer’s, it’s not a foregone conclusion, indicating that there are other factors at play. Indeed, a recent study has discovered that a rare genetic variation in the fibronectin 1 (FN1) gene can protect people with the ApoE 4 gene from its Alzheimer’s-inducing effects.
The genetic contribution to other types of dementia is less well understood but generally thought to be lower than in Alzheimer’s disease. Pathological variants of the SNCA and SNCB genes, which code for the proteins alpha and beta synuclein, are known to cause inherited forms of Lewy body dementia. However, they are thought to account for only about 10% of cases.
Frontotemporal lobar degeneration is thought to be sporadic (i.e., without an apparent cause) in up to 70% of cases. However, three genes associated with the condition have been identified: tau, progranulin, and C9ORF72. These three genes are thought to contribute to up to 30% of cases with a family history of the condition.
Overall, studies have identified many more genetic markers linked to an increased risk of developing dementia, most of which are associated with our bodies’ response to the ageing processes. Variation among such genetic networks may determine peoples’ risk of developing dementia earlier, say in their 70s or 80s, or not at all during their lifetime.
Boosting brain function with exercise
Dr Tara Walker
Physical exercise has long been known to positively affect neurogenesis—the generation of new neurons— and, thus, how our brain works. The underlying mechanisms, however, remain unknown. As the leader of the Systemic Brain Rejuvenation Group at QBI, Dr Tara Walker spearheads efforts to unravel this mystery and develop strategies to harness the powers of exercise to maintain or improve our cognitive function in normal ageing or dementia.
Neurogenesis affects memory formation and learning. It peaks during early development but is maintained at a low level throughout life, albeit ever decreasing with age. Neurogenesis in adults is most strongly associated with an area of the brain known as the hippocampus. This region is severely affected by some types of dementia, most notably Alzheimer’s disease, which causes neurogenesis to slow significantly or come to a halt altogether.
Dr Walker believes deciphering the mechanisms underlying exercise-induced neurogenesis could identify therapeutic targets to help maintain or improve cognitive function during normal ageing or in people living with dementia.
“Exercise strongly increases adult neurogenesis and enhances cognition, but the mechanisms were unknown. We study these mechanisms to develop novel exercise-mimicking treatments that reverse neuronal loss associated with physiological ageing, stroke, motor neurone disease and Alzheimer's, especially in people who cannot exercise, such at the very elderly or frail."
Our research has identified two novel strategies to increase neurogenesis and improve cognitive function, exercise-induced platelet activation and dietary selenium supplementation.
"We showed that platelets, the small blood cells that are most well known for their role in wound healing, can mediate the neurogenesis-enhancing effects of exercise. Specifically, we found that a single platelet-derived factor (platelet factor 4, PF4) can mimic exercise, enhance neurogenesis, and reverse age-related cognitive decline. Now, we are investigating whether PF4 can also reverse the cognitive decline in mouse models of Alzheimer’s disease.”
"We also found that dietary selenium supplementation can enhance adult hippocampal neurogenesis by modulating a process known as selenium-mediated ferroptosis, a form of programmed cell death to reverse the learning and memory deficits associated with ageing and stroke.”
NEUROGENESIS: The process of generating new neurons from neural stem cells. Primarily occurring in the hippocampus, adult neurogenesis is instrumental in learning and memory. It persists throughout life, but declines with age, and is severely impacted by some dementias.
COGNITION: a collective term that refers to those sensory and mental processes involved in perceiving, interpreting, storing, and using information through paying attention, memory, language, reasoning, problem-solving, decision-making, and adapting to new situations.
Professor Tanya Buchanan
Dementia is predicted to soon become the leading cause of death for Australians. For Dementia Australia CEO and Honorary Professor of Practice (Public Health) at the University of Wollongong, Professor Tanya Buchanan, meeting this challenge will require a dual approach focusing on brain health as well as providing more targeted, effective support to people impacted by dementia.
"Dementia is the second leading cause of death in Australia. There are an estimated 433,000 people currently living with dementia, a figure that is projected to almost double in the next 30 years.”
Research from the 2024 update of the Lancet Commission on the prevention, treatment and care of dementia reports that almost half of dementia cases worldwide could be prevented or delayed. They identified that the 14 modifiable risk factors that occur across the life course starting in childhood, underscoring the need for a public health approach to dementia prevention activities.
“While we cannot change getting older, modify our genetics or family history, it is now clear that a significant number of dementia cases can be prevented or delayed by addressing modifiable risk factors."
“Addressing these risk factors, using a public health approach to brain health that incorporates health equity, is crucial to addressing the expected rise in dementia numbers in the future. It requires government investment in education campaigns and a commitment to addressing the social and commercial determinants of health.”
Professor Buchanan says health professionals have a key role in highlighting modifiable risk factors and helping people diagnosed with dementia live well for longer.
“Appropriate post-diagnostic support and interventions can slow the progression of cognitive and functional decline, improve quality of life and delay or prevent residential aged care admission.”
By assessing physical and cognitive issues, health professionals can provide interventions to support the maintenance of current strengths and capabilities, improve skill acquisition and promote recovery, enablement and rehabilitation.
Lowering your risk of dementia
While scientists are striving to develop treatments or therapies for dementia, these treatments may only slow disease progression or help manage some of the effects of the underlying conditions. There is no cure yet.
Risk factors increase the likelihood of disease occurring. The most significant risk factors for developing dementia—age and genetics—are beyond our control. However, studies show that many health and lifestyle choices impact our risk of developing dementia. According to the Lancet Commission report on dementia prevention, intervention, and care 2024, up to 45% of future dementia cases could be prevented by addressing risks arising from our health and lifestyle choices.
Medical attention
Specific sensory impairments, such as hearing loss and vision impairments, as well as mental health conditions like depression, may increase dementia risk if not adequately addressed. To mitigate these risks, the Lancet Commission advises always using hearing aids if needed and preventing hearing damage by wearing protective gear if you are exposed to loud noises. Stick to your schedule for regular eye check-ups and use corrective glasses if prescribed. Likewise, mental health problems, such as depression, should be addressed by seeking professional care.
Cardiovascular health
Cardiovascular health is strongly linked to dementia risk, particularly Alzheimer’s disease. High blood pressure, high LDL cholesterol, diabetes, stroke, and heart disease increase the risk by potentially interfering with brain circulation and nutrient supply. Maintaining good cardiovascular health by managing weight, blood pressure, diabetes control, and low LDL cholesterol levels through exercise, a healthy diet, or, if needed, medication (e.g., to manage blood pressure) is imperative.
Lifestyle choices
Some lifestyle choices can significantly increase our dementia risk. Smoking, drinking, lack of exercise, and even air pollution have been linked with an increased risk of developing dementia, likely through their impacts on cardiovascular health. However, physical exercise has been shown to positively impact cognition by reducing cardiovascular risks and stimulating the formation of new neurons in the hippocampus
Social engagement
Social engagement increases mental activity and emotional connections to others and can help strengthen memory pathways. Recent studies have found that social isolation, especially among older people, can increase the risk of developing dementia by up to 27%. Social isolation not only increases dementia risk, but it also increases the risk of hypertension, depression and coronary heart disease, which may compound dementia risk. Therefore, staying socially active and engaged, especially in old age, is vital.
Diet and nutrition
Studies have shown that following a healthy diet—eating lots of fruit, vegetables, legumes and nuts; replacing butter with olive oil; eating fish; reducing salt use by using herbs and spices; and limiting red meat—is associated with lower dementia risk. Processed foods with high fats and trans fats are associated with an increased dementia risk.
Education and continued learning
Research increasingly suggests that a higher quality of education, especially during early life, is tied to a decreased dementia risk. However, continuous learning and educational attainment during adulthood and even in old age, have been shown to help maintain cognitive abilities and lower the risk of developing dementia. It’s worth noting, however, that experts question the benefit of puzzles or quizzes and instead recommend learning complex new skills such as a new language or an instrument.
Sleep
Sleep plays a crucial role in memory consolidation, and a lack of sleep can impact memory formation. Moreover, studies have found that as little as one night of sleep deprivation (of slowwave or deep sleep) can increase amyloid-beta levels. In contrast, chronic sleep deprivation has been linked to an increased spread of tau aggregates in the brain, thus possibly exacerbating Alzheimer’s pathology. Sleep disturbances, meanwhile, are increasingly believed to foreshadow the future development of Alzheimer’s even before cognitive changes are apparent.
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