Dementia overview

Michael Inskip PhD, ESSAM AEP


Dementia is a degenerative neurological condition that involves the progressive loss of neurons (brain cells) within the brain, which then causes a gradual decline in cognition (thinking) and functional independence (Reisberg, 2006). Currently, it is the most prevalent neurodegenerative condition—estimated to affect over 44 million people worldwide—and is expected to increase to 131 million affected people by 2050 (Prince et al., 2015). In Australia, over 400,000 people live with dementia, with similar increases expected over the next 30 years to 1.1 million affected people by 2050 (Brown et al., 2017). Additionally, while it important to note that dementia is not a normal part of ageing, its prevalence does increase dramatically with age due to the increased vulnerability of the brain to underlying degeneration and disease burden. The prevalence of dementia by age group increases from approximately 5-10% in the 70-80 years of age bracket, up to 30% in those aged over 100 years of age (Nichols et al., 2019).  An increase in population and a general shift towards an ageing population, in conjunction with advances in treatments and typical life expectancy are driving this increase at both a global and national level (Nichols et al., 2019). Consequently, it is estimated that in Australia alone, the total cost of dementia to the economy is AUD10 billion, rising to over AUD24 billion in the next 30 years (Brown et al., 2017).


The term dementia is often viewed as synonymous with Alzheimer’s disease, and incorrectly used interchangeably in public discourse, the media, and even in healthcare. Dementia is in fact an umbrella term for over 100 different underlying diseases and degenerative processes which can cause the pattern of progressive decline in cognition and function that is observed in the clinic (Brown et al., 2017). Disease processes that can cause dementia include Alzheimer’s disease, cerebrovascular disease, Lewy body disease, frontotemporal degeneration, and many other rarer causes such as HIV, Huntington’s disease, alcoholism and viral infections such as meningitis, to name a few. While it is increasingly understood that multiple disease processes may be contributing to the symptoms of dementia, the true extent of each cannot be determined while the person is living, so the dementia is therefore often named after the disease process likely to be contributing the most (Irwin et al., 2017). The most common dementia types therefore include Alzheimer’s disease dementia (contributing to 60-70% of all cases), vascular dementia (10%), Lewy body dementia (5-20%), and frontotemporal dementia (10%)(Brown et al., 2017; McKeith et al., 2017).

Etiology & Prognosis

The risk of developing dementia is a complex and difficult concept to map. However, what is clear is that risk factors are accrued throughout the lifespan starting from before birth right up until the point of diagnosis (Livingston et al., 2020).  Additionally, the processes that causes dementia can begin up to decades before there are even any noticeable symptoms (Beason-Held et al., 2013). While most dementia is considered sporadic, or randomly occurring, there are a handful of genes that make a small contribution to an increased risk of dementia. These include genes such as APOE4, SCNA, and PARK4, to name a few, which do not cause dementia, but likely increase the vulnerability of the individual to other risk factors throughout life, which accumulate and increase the risk of disease (Orme et al., 2018).

In early life, disruption of normal childhood development and less education can predispose an individual to dementia, mostly through decreasing what is known as cognitive reserve (Livingston et al., 2020; Wang et al., 2017). Cognitive reserve refers to level of cognitive ability and structural resilience of the brain above and beyond what is needed for independent function. Effectively, it represents a buffer in brain function whereby it can handle higher levels of damage from underlying disease for longer before reaching a critical threshold whereby the individual experiences symptoms (Fleming et al., 1995; Valenzuela & Sachdev, 2006; Wang et al., 2017). Other well known risk factors for dementia in mid and late life include concussion, hypertension (high blood pressure), alcoholism, obesity, smoking, depression, social isolation, physical inactivity, diabetes, air pollution and other neurological diseases (Ashby-Mitchell et al., 2017; Livingston et al., 2020). Promisingly, it is estimated that between 40-48% of the risk of developing dementia can be modified through readily accessible changes to lifestyle (Ashby-Mitchell et al., 2017; Livingston et al., 2020)

Mild cognitive impairment (MCI) is a stage just prior to dementia known as a prodromal stage (Gauthier et al., 2006). In this stage, individuals are concerned about mild impairments in cognition that are supported by cognitive tests but are yet to experience any significant dysfunction in daily life from this impairment. This stage represents a unique target for treatment as individuals with MCI are indeed more vulnerable to transitioning to dementia at up to six times more likely to than their cognitively-intact counterparts (Boyle et al., 2006). However,  between 16-44% of individuals with MCI may also revert back to ‘cognitively normal’ within a year of diagnosis, indicating that the processes contributing to the progressive decline may be in some part reversible in the earliest of stages and also partly due to the sensitivity of testing (Gao et al., 2018; Koepsell & Monsell, 2012). In fact, there are many potentially reversible causes of cognitive impairment such as thyroid dysfunction, vitamin B12 deficiency, dehydration, and infection, to name a few, which if treated, often alleviate any cognitive symptoms and should also be monitored throughout dementia (Fleming et al., 1995).

At the time of dementia diagnosis, a tipping point has been reached whereby the burden of the underlying damage to the neurons in the brain causes significant impairments in everyday life which progressively get worse over time. People living with dementia typically have four other comorbidities on average, compared with those living without the disease. Common comorbidities include hypertension (53%), pain conditions (34%), depression (24%), diabetes, stroke and visual impairments (17-18%) (Bunn et al., 2016; Scrutton & Brancati, 2016). Furthermore, people living with dementia have an incidence of falls eight times greater than those who are cognitively intact  (Allan et al., 2009), a two times greater risk of sustaining an injury from a fall (Jørgensen et al., 2015), are 15% more likely to be hospitalised due to that fall (Harvey et al., 2016), are 43% more likely to be admitted to hospital for any cause (Shepherd et al., 2019) and almost twice as likely to die during admission (Fogg et al., 2017). Additionally, the prevalence of frailty even in those with mild dementia is already as high as 37%, with Lewy body dementia (LBD) having the highest risk of frailty (Borda et al., 2019).

The life expectancy from diagnosis varies greatly and is influenced both by the type of dementia and a diverse array of risk factors accrued throughout life and during the disease process. Generally, for the most common types of dementia there is a reported mean life expectancy of around 7-10 years from diagnosis, with an estimated transition to residential aged care for one-fifth of affected persons 2-3 years after diagnosis (Mjørud et al., 2020; Mueller et al. 2017). Established risk factors which predict a more rapid decline include being male, older at diagnosis, and having more functional impairments, comorbidities, Parkinsonism, multiple disease pathologies, high risk medications, malnutrition, frailty and sarcopenia, to name a few (Mueller et al., 2017). Similar to the risks factors for developing dementia, many of these risk factors are potentially modifiable through a combination of lifestyle changes, supportive care and early treatment and can improve and maintain quality of life and independence in dementia for a longer duration. However, our current understanding is that underling disease process causing dementia continues mostly unaltered by treatments and eventually the person will die from complications in the end stages of disease, as dementia is a terminal diagnosis (Galimberti & Scarpini, 2011). Often this comes about through complications resulting from weakened input from the brain to organs such as the lungs, leading to pneumonia and infection (Degerskär & Englund, 2020).


Diagnosis of dementia is a clinical diagnosis, meaning that it cannot be diagnosed by a single test such as a scan or blood test. Instead, dementia is diagnosed by trained physicians, general practitioners and/or psychologists through thorough examination of the person and gathering a comprehensive history. The common diagnostic feature among all dementias is a progressive loss of cognitive function from previous levels which leads to a functional impairment in daily living (Reisberg, 2006).

Determining cognitive decline often relies on cognitive tests completed in the clinic, as well as reports from the person or their caregiver (proxy/informant) of their previous level of cognition. Determining the level of functional impairment is also determined through questions asked to both person and informant. The pattern and history of cognitive impairment in conjunction with the presence of other motor (movement), psychiatric (mood) and autonomic (regulation) symptoms can help to further refine the type of dementia. Imaging, blood tests, biopsies, nerve conduction studies and genetic testing may also be performed depending on the circumstances to support diagnosis of a certain type of dementia, as well as rule out other potential reversible causes previous mentioned (Fleming et al., 1995; Reisberg, 2006). The clinical diagnosis is sufficient for the purposes of determining prognosis and initiating appropriate treatment. However, the qualifying terms ‘probable’ and ‘possible’ in research and some clinical settings placed in front of the diagnosis reflects the level of certainty the clinician has regarding the underlying disease process that is causing the dementia (McKeith et al., 2017). The pathological cause of the dementia is only able to be confirmed on autopsy (after death) by examining the pathology present within the brain, however the majority of individuals will never undergoing this process.

Following diagnosis, the severity of dementia can be classified using a variety of tools and classification systems. Broadly, dementia is categorised into mild, moderate, severe, and end stage (van den Dungen et al., 2012). The stages typically reflect either the level of cognitive dysfunction on testing or the level of functional impairment in daily tasks, or a combination of both. The Clinical Dementia Rating (CDR) scale is a common tool used to classify dementia and is scored on a combination of cognitive and functional impairment in the domains of memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care (Morris, 1997). Diagnosing and staging dementia can be challenging as the tool used can lack sensitivity (i.e. not pick up subtle changes), and reports of previous levels of cognition and function can often be missing or unreliable (De Lepeleire et al., 2004).

Pathophysiology & Morphology

The processes underlying dementia vary greatly, but ultimately at the neuronal level the pathology leads to cellular dysfunction and impaired metabolism, impaired communication between cells (known as synaptic transmission) and then eventually cell death (Cunningham et al., 2015). In some dementias, the abnormal accumulation of certain proteins within the cell body of the neuron, and/or the cells that support the neuron (glia) cause a cascade of dysfunction leading to cell death, wherein other dementias an error in producing a certain protein, viral damage to the cell, or damage to blood vessels supplying the neuron contribute. Not only can many of these processes occur simultaneously, but they can also alter the cellular environment within the brain, increasing local inflammation which in turn impairs cellular function, altering gene expression and the process of neurogenesis (creation of new neurons) (Cunningham et al., 2015).

In the most common type of dementia, Alzheimer’s disease dementia, the main pathologies are the proteins amyloid beta and tau, which form plagues (known as amyloid plaques) and tangles (known as neurofibrillary tangles) inside the cells of the neuron and glia, respectively. However, there is also extensive cerebrovascular damage observed in Alzheimer’s disease which can be similar to that noted in vascular dementia, whereby blood vessels become stiffer, lesions occur in blood supply at a micro level, and inflammatory markers are elevated within the brain (Santos et al., 2017). In addition, the Lewy body dementias involve clumps of alpha synuclein protein (known as Lewy bodies) inside the cell that cause dysfunction and death and also often show signs of the Alzheimer’s disease pathology and cerebrovascular pathology described above on autopsy (Mueller et al., 2017). Thus, the processes that lead to dementia are increasingly understood to be a complex combination of abnormal protein accumulation, vascular impairment, inflammation, gene regulation and impaired neurogenesis within the brain (Irwin et al., 2017).

To make matters more complicated, the amount of pathology present within the brain of an individual may not always correlate to the cognitive symptoms experienced or the severity of dementia while living (SantaCruz et al., 2011; Valenzuela & Sachdev, 2006).  The cognitive reserve and grey matter (neuron cell bodies) volume of the individual may play a significant part in how the disease manifests (Arnold et al., 2013). For instance, there are associations between lower volumes of grey matter, higher levels of cerebrovascular damage and the severity of dementia (Stout et al., 1996). Additionally, certain regions of the brain are particularly vulnerable to insult or damage from underlying disease processes more so than others (Stout et al., 1996; Suzuki et al., 2019). Examples include small areas of the mid brain that contribute to fundamental cognitive processes such as the hippocampus (a hub for memory formation and retrieval) and basal ganglia (motivation, movement), as well as larger areas such as frontal lobe which is involved in decision making, attention and personality (Forrest et al., 2019; Mueller et al., 2017; Suzuki et al., 2019). The general pattern that is observed is atrophy (shrinkage) of these regions ascertained through imaging as well as on autopsy, which corresponds to the cluster of symptoms experienced by the individual.

In addition, a loss of neuronal mass, decreased metabolism and a decrease in the production of key neurotransmitters (chemicals involved in sending signals between neurons) in these regions lead to functional changes in how the neurons connect and communicate with each other, as well as the blood supply to that area to supports this activity (known as hypoperfusion) (Chabran et al., 2020; Mueller et al., 2017; Schumacher et al., 2019). The ability of the brain to resist or adapt to the pathological damage of dementia is believed to reduce with disease progression as well as with normal ageing (Ebaid & Crewther, 2020; Kumar et al., 2017). Several theories attempt to explain the early adaptations of the brain in dementia, such as recruiting more diffuse networks of neurons to perform tasks, albeit less efficiently (Ebaid & Crewther, 2020). However early in the disease course, at the MCI or early dementia stage, non-pharmacological treatments such as exercise can positively alter the size and functional connectivity of key brain structures indicating that neuroplasticity is possible even amid a backdrop of degenerative disease (Ahlskog et al., 2011; Broadhouse et al., 2020; Herold et al., 2019). The extent to which the brain can resist the disease pathology varies and is still largely unknown. However, treatments can build resilience within these networks and in some cases restore, albeit temporarily, the imbalance of neurotransmitters within these damaged regions. The complex and multifaceted nature of dementia means that treatments are unlikely to work in isolation, and a combination of pharmacological and non-pharmacological treatment strategies are required.


Treatments for disease generally fall into four categories: curative (complete reversal), disease-modifying (change the course of pathology), symptomatic management (treat the symptoms of the disease), and preventative (reduce the risk of disease occurring). Currently, there is no cure for dementia. Furthermore, the majority (99.6%) of medications trialled for the treatment of dementia through targeting the pathology have ultimately failed in human trials (Cummings et al., 2014). This may be due to a combination of reasons including, but not limited to highly variable cohorts, targeting only one component of a complex disease, as well the possibility that starting treatments when someone has symptoms may be too late to significantly modify the underlying disease process. Up until very recently there have also been no disease-modifying treatments available that alter the progression of the underlying pathology. A recent medication approved for use in the US has been surrounded by controversy and shown relatively weak evidence that it modifies the disease course in individuals with dementia with more trials needed to explore this finding (Thomas et al., 2021). The majority of treatments for dementia are therefore either aimed at lowering the risk of developing dementia, or treating the variety of symptoms that are observed within dementia (Cunningham et al., 2015).

In regards to prevention, recent modelling in Australia suggests that reducing the yearly incidence of dementia by as little as 5% could lead to reductions in the estimated amount of people living with the disease in the next 35 years of up to 24% and save up to $120.4 billion cost to the economy (Brown et al., 2017). This could be achieved through addressing the modifiable risk factors mentioned previously through changes in lifestyle and managing other chronic diseases effectively. However, for those living with dementia currently, symptomatic treatments are the only type of treatment accessible and can have significant impacts on quality of life and longevity, especially early in the disease course (Cunningham et al., 2015). A feature of the literature in non-pharmacological, and to a lesser extent, pharmacological treatments is that often the results are mixed in terms of effectiveness due to variation in how the treatment is applied and the diversity among people living with dementia in what is a complex disease. All treatments should be discussed with a doctor to develop a strategy appropriate for the unique circumstances of each person living with dementia.


Currently, there are limited symptomatic treatments for dementia. The goal of treatment is to slow down the development of symptoms and preserve memory and function for as long as possible and reduce behavioural disturbances to delay transition into residential aged care. Medications are prescribed only when the potential benefits for the individual are perceived to outweigh the risks by the treating team.

Currently there are two main classes of medications used to improve cognition; acetylcholinesterase inhibitors (AChE) and NMDA receptor agonists (Cunningham et al., 2015). The former includes common medications such as rivastigmine, galantamine and donepezil, which work to slow down the breakdown of the neurotransmitter acetylcholine in the synapse (connection between neurons), which is depleted in dementia. The latter includes the medication memantine which works to antagonise (impair) the function of the NMDA receptor in the synapse and prevent a build-up of another neurotransmitter glutamate, which in excess is believed to contribute to toxicity and the dysfunction of neuron. The effects of these medications are generally positive, however results vary for each individual and by dementia subtype (Cunningham et al., 2015). A review and meta-analysis (combination of data) of available clinical literature indicates that AChE medications provide a modest, clinically significant improvement on common measures of cognition at least over a 12 month period, which translates to around a sustained one point increase on a common measure of cognition, the mini-mental state exam (MMSE) (Knight et al., 2018). For memantine, the treatment effects were smaller and more varied, with some experiencing larger gains and some no benefit at all (Knight et al., 2018). In addition, these effects are studied predominantly within Alzheimer’s disease dementia, with the literature on the effects of these medications on other types of dementia limited, of lower quality and mixed outcome (Cunningham et al., 2015).

In addition to the medications used to treat cognition, commonly medications are prescribed to help manage behavioural symptoms in dementia. Antidepressant medications such as selective serotonin reuptake inhibitors (SSRI’s) including citalopram, sertraline, and atypical antidepressants such as mirtazapine are often prescribed within dementia to treat depression (Cunningham et al., 2015). A recent review found high quality evidence of little or no effect of these medications on depression scores in dementia over a few months compared to a placebo group, and moderate quality evidence that there was no long term benefit. However, those who experienced remission from depression (symptoms no longer present) were more likely to have been on medications when this occurred (Dudaset al., 2018). However, the effects between individuals can vary significantly and these medications may be beneficial for individuals after discussion with their physician. Other medications for behavioural disturbances in dementia include atypical antipsychotics or neuroleptics such as risperidone which are used for irritability and aggression, and benzodiazepines such as clonazepam used to relax and calm anxiety (Cunningham et al., 2015).

The use of neuroleptic medications in Alzheimer’s disease dementia is associated with an increased risk of faster disease progression and earlier mortality, and its prescription in other forms of dementia such as Lewy body dementia is not recommended due to the high risk of adverse events (Mueller et al., 2017). Medications may also be used for specific types of dementia to treat symptoms or comorbidities associated with that condition. Dopaminergic medications which increase the level of dopamine, a neurotransmitter involved in motivation and movement, may be used in Lewy body dementia due to the presence of Parkinsonism, however is often discontinued due to its exacerbation of hallucinations and delusions (Mueller et al., 2017). Antiplatelet medications may be used for vascular dementia to reduce the risk of further stroke and damage to the vessels within the brain. Melatonin, a natural occurring substance within the brain which promotes restfulness and sleep, may also be supplemented as a lower risk option to improve disrupted sleep cycles in those with dementia.

Lastly, but perhaps most importantly, an important pharmacological strategy in dementia is the deprescription (removal) of medications which may no longer be beneficial to the person with dementia, particularly if there are side effects which outweigh the benefits. Potentially inappropriate medications (PIMs) are common in adults with dementia, with 66% of those living in the community with dementia estimated to have at least one PIM (Bala et al., 2019), while over 80% of those in residential aged care meet this criteria (Eshetie et al., 2020). Additionally, those with dementia subtypes such as Lewy body dementia are 50% more likely to have PIMs than those with Alzheimer’s disease dementia (Ramsey et al., 2018). The presence of PIMs is a risk factor for the development of frailty in those with dementia, as well as an increased risk of falls and mortality (Mueller et al., 2018). The current Australian guidelines recommend that to treat frailty the deprescription of hazardous medications where appropriate must occur in conjunction with robust exercise and dietary fortification (Dent et al., 2017). Specialist aged care physicians, called geriatricians, work with the treating team to minimise or substitute hazardous and ineffective medications where possible to improve outcomes for the person with dementia.

Non-pharmacological & supportive care

In the recent decade there has been a renewed focus on non-pharmacological treatments for dementia due to consistently small to moderate effects on cognition, behaviour and in particular functional independence relating to mobility, transferring and performing everyday activities of living (ADLs). Supportive care involves the use of technology, home modification and medical care to enable the individual to maintain independence for as long as possible and manage complications.  Thus, the main goal of non-pharmacological treatments are to improve quality of life for the individual and enable ‘ageing in place’, which is not only a government policy but a best practice initiative to support the person living with dementia in their home and delay transition to residential aged care where possible. Ageing in place not only reduces the stress of transition for the person with dementia, but enables the existing network of support to remain in place, while being more cost effective for the family and government in the long run (Vreugdenhil, 2014). Additionally, compared to those who transition to residential aged care, outcomes relating to cognition, depression and incontinence are maintained for those ageing in place (Luker et al., 2019). However, the decision to remain in place or move to aged care is highly individual and must be weighed up by the person with dementia, their caregiver and the treating team.

The main, most accessible non-pharmacological treatment for dementia and the comorbid frailty that develops with the disease and accelerates decline in cognition and function independence is exercise. Robust exercise can not only improve cognition throughout the lifespan but can increase the volume of key structures within the brain such as the hippocampus and broader cortex, as well as functioning of neural pathways that are susceptible to the damage in dementia (Ahlskog et al., 2011; Broadhouse et al., 2020; Herold et al., 2019).

In the prodromal stage of dementia mild cognitive impairment (MCI), exercise programs that  involve a component of progressive resistance training (PRT), a form of training which targets your strength, have small to moderate effects of cognition and are most effective at treating frailty (Gates et al., 2013). In those with dementia, it is important to include aerobic training (exercises that raise heart rate), PRT, as well as balance exercise to be most effective in improving and optimising cognition, managing comorbidity, and delaying the onset of frailty (Dent et al., 2017; Northey et al., 2018).

To maximise the effect of exercise, programs need to be ongoing and of a moderate to high intensity (at least enough to make you puff or feel as though you’re pushing a weight hard), while session length should be kept to under an hour in duration to avoid fatigue. Additionally, aerobic exercise especially those that are functional such as walking and/or require a cognitive challenge such as dancing, should be performed most days of the week. While PRT and balance should be performed at least 2–3 non-consecutive days per week. As dementia progresses and frailty develops in those who are at risk of becoming bed-bound, the importance of anabolic exercise modalities such as PRT and balance increases and it becomes vital that frequent, shorter bouts of walking or other aerobic exercise are performed throughout the day to avoid prolonged period of sedentary activity (Dent et al., 2017). It is well established that frailty has an effect on cognition in part separate to the underlying disease pathology (Buchman et al., 2014; Wallace et al., 2019). Thus, it is vital that exercise programs includes resistance training to provide the anabolic stimulus required to treat frailty, which is readily amenable to the robust exercise, dietary fortification and deprescribing of hazardous medications (Dent et al., 2017). Exercise should form an integral part of all treatment strategies for dementia and organising a consult with an Accredited Exercise Physiologist (AEP), who specialises in the prescription of effective exercise for chronic conditions is a good strategy to ensure you are getting the optimal benefits from exercise.

Additional non-pharmacological treatments such as cognitive training (CT), cognitive behavioural therapy (CBT), reminiscence therapy (RT) and music therapy may also be helpful in the treatment of dementia. Cognitive training involving challenging tasks targeting areas of impairment may provide some small improvements in cognition for those with mild to moderate dementia, however the outcomes reported in the literature are mixed (Bahar‐Fuchs et al., 2019) . A practical application of cognitive training may be to learn a new skill which requires sustained attention and practice. A small base of literature has found a small but significant positive effects on cognition in those with mild dementia who take up a new, stimulating task and practice it weekly (Park et al., 2014). Cognitive behavioural therapy (CBT), which involves improving awareness about conditions and actions, may provide moderate benefits for reducing stress and anxiety in those with mild dementia. However, these benefits may be limited to those in the early disease stages  (Tay et al., 2019).  Reminiscence therapy, which involves sharing life experiences and memories, has been reported to have small effects on quality of life and cognition but it is unclear if these effects translate into noticeable changes in everyday life (Woods etal., 2018). Likewise, music therapy which involves the use of music to increase engagement in activities and mood, has small but significant effects on quality of life, and depressive symptoms but not on cognition (van der Steen et al., 2018). It is unclear what benefits remain beyond short term (less than a month) use.

For many of these non-pharmacological therapies for behaviour and quality of life, the effects will vary from individual to individual and are hard to capture in the research. Ultimately, if the intervention is enjoyable and can lead to a positive outcome for the person with dementia, albeit for a limited time, then these therapies should be considered.


Dementia is an umbrella term for a range of diseases that cause progressive cognitive decline and functional impairment. While not a normal part of ageing, the prevalence of dementia does increase with age, and with a general shift to an ageing population and longer lifespan, the number of people living with dementia is expected to rise steadily from 44 million globally to 115 million by 2050. The symptoms of dementia are diverse, extending beyond the stereotypical problems with memory to include psychiatric, autonomic, and even motor symptoms depending on the sub-type of dementia. Additionally, there is a high burden of comorbidities in dementia including the high prevalence of frailty that requires a targeted pharmacological and non-pharmacological treatment strategy individualised to the person. The core aim of treatment is to optimise quality of life and longevity in the disease course, minimise frailty, and delay transition to higher care for as long as possible with a focus on ageing in place.



Ahlskog, J. E., Geda, Y. E., Graff-Radford, N. R., & Petersen, R. C. (2011). Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clinic Proceedings, 86(9), 876–884.

Allan, L. M., Ballard, C. G., Rowan, E. N., & Kenny, R. A. (2009). Incidence and prediction of falls in dementia: A prospective study in older people. PLOS ONE, 4(5), e5521.

Arnold, S. E., Louneva, N., Cao, K., Wang, L.-S., Han, L.-Y., Wolk, D. A., Negash, S., Leurgans, S. E., Schneider, J. A., Buchman, A. S., Wilson, R. S., & Bennett, D. A. (2013). Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease. Neurobiology of Aging, 34(1), 157-168.

Ashby-Mitchell, K., Burns, R., Shaw, J., & Anstey, K. J. (2017). Proportion of dementia in Australia explained by common modifiable risk factors. Alzheimer’s Research & Therapy, 9(1), Article 11.

Bahar‐Fuchs, A., Martyr, A., Goh, A. M., Sabates, J., & Clare, L. (2019). Cognitive training for people with mild to moderate dementia. Cochrane Database of Systematic Reviews.

Bala, S. S., Jamieson, H. A., & Nishtala, P. S. (2019). Determinants of prescribing potentially inappropriate medications in a nationwide cohort of community dwellers with dementia receiving a comprehensive geriatric assessment. International Journal of Geriatric Psychiatry, 34(1), 153-161.

Beason-Held, L. L., Goh, J. O., An, Y., Kraut, M. A., O’Brien, R. J., Ferrucci, L., & Resnick, S. M. (2013). Changes in brain function occur years before the onset of cognitive impairment. Journal of Neuroscience, 33(46), 18008-18014.

Borda, M. G., Soennesyn, H., Steves, C. J., Vik-Mo, A. O., Pérez-Zepeda, M. U., & Aarsland, D. (2019). Frailty in older adults with mild dementia: Dementia with Lewy bodies and Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders Extra, 9(1), 176-183.

Boyle, P., Wilson, R., Aggarwal, N., Tang, Y., & Bennett, D. (2006). Mild cognitive impairment: Risk of Alzheimer disease and rate of cognitive decline. Neurology, 67(3), 441-445.

Broadhouse, K. M., Singh, M. F., Suo, C., Gates, N., Wen, W., Brodaty, H., Jain, N., Wilson, G. C., Meiklejohn, J., Singh, N., Baune, B. T., Baker, M., Foroughi, N., Wang, Y., Kochan, N., Ashton, K., Brown, M., Li, Z., Mavros, Y. … Valenzuela, M. J. (2020). Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. NeuroImage Clinical, 25, Article 102182.

Brown, L., Hansnata, E., & La, H. A. (2017). Economic cost of dementia in Australia 2016-2056: Report prepared for Alzheimer’s Australia.

Buchman, A. S., Yu, L., Wilson, R. S., Boyle, P. A., Schneider, J. A., Bennett, D. A., & Kritchevsky, S. (2014). Brain pathology contributes to simultaneous change in physical frailty and cognition in old age. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 69(12), 1536-1544.

Bunn, F., Burn, A.-M., Goodman, C., Robinson, L., Rait, G., Norton, S., Bennett, H., Poole, M., Schoeman, J., & Brayne, C. (2016). Comorbidity and dementia: A mixed method study on improving healthcare for people with dementia (CoDem). Health Services and Delivery Research, 4(8).

Chabran, E., Noblet, V., Loureiro de Sousa, P., Demuynck, C., Philippi, N., Mutter, C., Anthony, P., Martin-Hunyadi, C., Cretin, B., & Blanc, F. (2020). Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: Implications for fluctuations. Alzheimer’s Research & Therapy, 12, Article 9.

Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures. Alzheimer’s Research & Therapy, 6, Article 37. 

Cunningham, E. L., McGuinness, B., Herron, B., & Passmore, A. P. (2015). Dementia. The Ulster Medical Journal, 84(2), 79-87.

De Lepeleire, J., Aertgeerts, B., Umbach, I., Pattyn, P., Tamsin, F., Nestor, L., & Krekelbergh, F. (2004). The diagnostic value of IADL evaluation in the detection of dementia in general practice. Aging & Mental Health, 8(1), 52-57.

Degerskär, A., & Englund, E. (2020). Cause of death in autopsy‐confirmed dementia disorders. European Journal of Neurology, 27(12), 2415-2421.

Dent, E., Lien, C., Lim, W. S., Wong, W. C., Wong, C. H., Ng, T. P., Woo, J., Dong, B., de la Vega, S., Hua Poi, P. J., Kamaruzzaman, S. B.., Won, C., Chen, L.-K., Rockwood, K., Arai, H., Rodriguez-Mañas, L., Cao, L., Cesari, M., Chan, P., … Flicker, L. (2017). The Asia-Pacific clinical practice guidelines for the management of frailty. Journal of the American Medical Directors Association, 18(7), 564-575.

Dudas, R., Malouf, R., McCleery, J., & Dening, T. (2018). Antidepressants for treating depression in dementia. Cochrane Database of Systematic Reviews.

Ebaid, D., & Crewther, S. G. (2020). Time for a systems biological approach to cognitive aging? A critical review. Frontiers in Aging Neuroscience, 12, 114.

Eshetie, T. C., Roberts, G., Nguyen, T. A., Gillam, M. H., Maher, D., & Kalisch Ellett, L. M. (2020). Potentially inappropriate medication use and related hospital admissions in aged care residents: The impact of dementia. British Journal of Clinical Pharmacology, 86(12), 2414-2423.

Fleming, K. C., Adams, A. C., & Petersen, R. C. (1995). Dementia: Diagnosis and evaluation.

Mayo Clinic Proceedings 70(11), 1093-1107,

Fogg, C., Meredith, P., Bridges, J., Gould, G. P., & Griffiths, P. (2017). The relationship between cognitive impairment, mortality and discharge characteristics in a large cohort of older adults with unscheduled admissions to an acute hospital: A retrospective observational study. Age and Ageing, 46(5), 794-801.

Forrest, S. L., Kril, J. J., & Halliday, G. M. (2019). Cellular and regional vulnerability in frontotemporal tauopathies. Acta Neuropathologica, 138, 705-727.

Galimberti, D., & Scarpini, E. (2011). Disease-modifying treatments for Alzheimer’s disease. Therapeutic Advances in Neurological Disorders, 4(4), 203-216.

Gao, Q., Gwee, X., Feng, L., Nyunt, M. S. Z., Feng, L., Collinson, S. L., Chong, M. S., Lim, W. S., Lee, T.-S., Yap, P., Yap, K. B., & Ng, T. P. (2018). Mild cognitive impairment reversion and progression: Rates and predictors in community-living older persons in the Singapore longitudinal ageing studies cohort. Dementia and Geriatric Cognitive Disorders Extra, 8(2), 226-237.

Gates, N., Singh, M. A. F., Sachdev, P. S., & Valenzuela, M. (2013). The effect of exercise training on cognitive function in older adults with mild cognitive impairment: A meta-analysis of randomized controlled trials. The American Journal of Geriatric Psychiatry, 21(11), 1086-1097.

Gauthier, S., Reisberg, B., Zaudig, M., Petersen, R. C., Ritchie, K., Broich, K., Belleville, S., Brodaty, H., Bennett, D., Chertkow, H., Cummings, J. L., de Leon, M., Feldman, H., Ganguli, M., Hampel, H., Scheltens, P., Tierney, M. C., Whitehouse, P., & Winblad, B. (2006). Mild cognitive impairment. The Lancet, 367(9518), 1262-1270.

Harvey, L., Mitchell, R., Brodaty, H., Draper, B., & Close, J. (2016). The influence of dementia on injury-related hospitalisations and outcomes in older adults. Injury, 47(1), 226-234.

Herold, F., Törpel, A., Schega, L., & Müller, N. G. (2019). Functional and/or structural brain changes in response to resistance exercises and resistance training lead to cognitive improvements: A systematic review. European Review of Aging and Physical Activity, 16, Article 10.

Irwin, D. J., Grossman, M., Weintraub, D., Hurtig, H. I., Duda, J. E., Xie, S. X., Lee, E. B., Van Deerlin, V. M., Lopez, O. L., Kofler, J. K., Nelson, P. T., Jicha, G. A., Woltjer, R., Quinn, J. F., Kaye, J., Leverenz, J. B., Tsuang, D., Longfellow, K., Yearout, D. … Trojanowski, J. Q. (2017). Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: A retrospective analysis. The Lancet Neurology, 16(1), 55-65.

Jørgensen, T. S. H., Hansen, A., Sahlberg, M., Gislason, G. H., Torp‐Pedersen, C., Andersson, C., & Holm, E. (2015). Nationwide time trends and risk factors for in‐hospital falls‐related major injuries. International Journal of Clinical Practice, 69(6), 703-709.

Knight, R., Khondoker, M., Magill, N., Stewart, R., & Landau, S. (2018). A systematic review and meta-analysis of the effectiveness of acetylcholinesterase inhibitors and memantine in treating the cognitive symptoms of dementia. Dementia and Geriatric Cognitive Disorders, 45(3-4), 131-151.

Koepsell, T. D., & Monsell, S. E. (2012). Reversion from mild cognitive impairment to normal or near-normal cognition: Risk factors and prognosis. Neurology, 79(15), 1591-1598.

Kumar, S., Zomorrodi, R., Ghazala, Z., Goodman, M. S., Blumberger, D. M., Cheam, A., Fischer, C., Daskalakis, Z. J., Mulsant, B. H., Pollock, B. G., & Rajji, T. K. (2017). Extent of dorsolateral prefrontal cortex plasticity and its association with working memory in patients with Alzheimer disease. JAMA Psychiatry, 74(12), 1266-1274.

Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C.,  Costafreda, S. G., Dias, A., Fox, N., Gitlin, L. N., Howard, R., Kales, H. C., Kivimäki, M., Larson, E. B., Ogunniyi, A. … Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413-446.

Luker, J. A., Worley, A., Stanley, M., Uy, J., Watt, A. M., & Hillier, S. L. (2019). The evidence for services to avoid or delay residential aged care admission: A systematic review. BMC Geriatrics, 19, Article 217.

McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J.-P., Weintraub, D., Aarsland, D., Galvin, J., Attems, J., Ballard, C. G., Bayston, A., Beach, T. G., Blanc, F., Bohnen, N., Bonanni, L., Bras, J., Brundin, P., Burn, D., Chen-Plotkin, A., … Kosaka, K. (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89(1), 88-100.

Mjørud, M., Selbæk, G., Bjertness, E., Edwin, T. H., Engedal, K., Knapskog, A.-B., & Strand, B. H. (2020). Time from dementia diagnosis to nursing-home admission and death among persons with dementia: A multistate survival analysis. PLOS ONE, 15(12), Article e0243513.

Morris, J. C. (1997). Clinical dementia rating: A reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. International Psychogeriatrics, 9(S1), 173-176.

Mueller, C., Ballard, C., Corbett, A., & Aarsland, D. (2017). The prognosis of dementia with Lewy bodies. The Lancet Neurology, 16(5), 390-398.

Mueller, C., Molokhia, M., Perera, G., Veronese, N., Stubbs, B., Shetty, H., Codling, D., Huntley, J., & Stewart, R. (2018). Polypharmacy in people with dementia: Associations with adverse health outcomes. Experimental Gerontology, 106, 240-245.

Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., Aichour, M. T. E., Akinyemi, R. O., Alahdab, F.,  Asgedom, S. W., Awasthi, A., Barker-Collo, S. L., Baune, B. T., Béjot, Y., Belachew, A. B., Bennett, D. A., Biadgo, B., Bijani, A., Bin Sayeed, M. S., … Murray, C. J. (2019). Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 88-106.

Northey, J. M., Cherbuin, N., Pumpa, K. L., Smee, D. J., & Rattray, B. (2018). Exercise interventions for cognitive function in adults older than 50: A systematic review with meta-analysis. British Journal of Sports Medicine, 52, 154-160.

Orme, T., Guerreiro, R., & Bras, J. (2018). The genetics of dementia with Lewy bodies: Current understanding and future directions. Current Neurology and Neuroscience Reports, 18, Article 67.

Park, D. C., Lodi-Smith, J., Drew, L., Haber, S., Hebrank, A., Bischof, N., & Aamodt, W. (2014). The impact of sustained engagement on cognitive function in older adults: The Synapse Project. Psychological Science, 25(1), 103-112.

Prince, M. J., Wimo, A., Guerchet, M., Ali, G.-C., Wu, y.-T., & Prina, M. (2015). World Alzheimer Report 2015: The global impact of dementia: An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International.

Ramsey, C. M., Gnjidic, D., Agogo, G. O., Allore, H., & Moga, D. (2018). Longitudinal patterns of potentially inappropriate medication use following incident dementia diagnosis. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 4, 1-10.

Reisberg, B. (2006). Diagnostic criteria in dementia: A comparison of current criteria, research challenges, and implications for DSM-V. Journal of Geriatric Psychiatry and Neurology, 19(3), 137-146.

SantaCruz, K. S., Sonnen, J. A., Pezhouh, M. K., Desrosiers, M. F., Nelson, P. T., & Tyas, S. L. (2011). Alzheimer disease pathology in subjects without dementia in 2 studies of aging: The Nun Study and the Adult Changes in Thought Study. Journal of Neuropathology & Experimental Neurology, 70(10), 832-840.

Santos, C. Y., Snyder, P. J., Wu, W.-C., Zhang, M., Echeverria, A., & Alber, J. (2017). Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 7, 69-87.

Schumacher, J., Peraza, L. R., Firbank, M., Thomas, A. J., Kaiser, M., Gallagher, P., O’Brien, J. T., Blamire, A. M., & Taylor, J.-P. (2019). Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer’s disease. NeuroImage: Clinical, 22, 101812.

Scrutton, J., & Brancati, C. (2016). Dementia and comorbidities: Ensuring parity of care. The International Longevity Centre.

Shepherd, H., Livingston, G., Chan, J., & Sommerlad, A. (2019). Hospitalisation rates and predictors in people with dementia: A systematic review and meta-analysis. BMC Medicine, 17, Article 130.

Stout, J. C., Jernigan, T. L., Archibald, S. L., & Salmon, D. P. (1996). Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. Archives of Neurology, 53(8), 742-749.

Suzuki, H., Venkataraman, A. V., Bai, W., Guitton, F., Guo, Y., Dehghan, A., & Matthews, P. M. (2019). Associations of regional brain structural differences with aging, modifiable risk factors for dementia, and cognitive performance. JAMA Network Open, 2(12), Article e1917257.

Tay, K. W., Subramaniam, P., & Oei, T. P. (2019). Cognitive behavioural therapy can be effective in treating anxiety and depression in persons with dementia: A systematic review. Psychogeriatrics, 19(3), 264-275.

Thomas, E., Wasunna‐Smith, B., & Kuruvilla, T. (2021). Aducanumab and disease modifying treatments for Alzheimer’s disease. Progress in Neurology and Psychiatry, 25(3), 4-6.

Valenzuela, M. J., & Sachdev, P. (2006). Brain reserve and dementia: A systematic review. Psychological Medicine, 36(4), 441-454.

van den Dungen, P., van Marwijk, H. W., van der Horst, H. E., Moll van Charante, E. P., MacNeil Vroomen, J., van de Ven, P. M., & van Hout, H. P. (2012). The accuracy of family physicians’ dementia diagnoses at different stages of dementia: A systematic review. International Journal of Geriatric Psychiatry, 27(4), 342-354.

van der Steen, J. T.,  van Soest-Poortvliet, M. C., van der Wouden, J. C., Bruinsma, M. S., Scholten, R. J., & Vink, A. C. (2018). Music‐based therapeutic interventions for people with dementia. Cochrane Database of Systematic Reviews.

Vreugdenhil, A. (2014). ‘Ageing-in-place’: Frontline experiences of intergenerational family carers of people with dementia. Health Sociology Review, 23(1), 43-52.

Wallace, L. M., Theou, O., Godin, J., Andrew, M. K., Bennett, D. A., & Rockwood, K. (2019). Investigation of frailty as a moderator of the relationship between neuropathology and dementia in Alzheimer’s disease: A cross-sectional analysis of data from the Rush Memory and Aging Project. The Lancet Neurology, 18(2), 177-184.

Wang, H.-X., MacDonald, S. W., Dekhtyar, S., & Fratiglioni, L. (2017). Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study. PLOS Medicine, 14(3), e1002251.

Woods, B., O’Philbin, L., Farrell, E. M., Spector, A. E., & Orrell, M. (2018). Reminiscence therapy for dementia. Cochrane Database of Systematic Reviews.