Modifiable Risk Factors for Dementia

Aging Population and Dementia

Older age is a key risk factor for Alzheimer's, but dementia isn't a normal part of aging. It's due to pathologies like Alzheimer's, cerebrovascular issues, and Lewy body pathology. Once these pathologies are accounted for, the direct correlation between old age and dementia diminishes.

Modifiable Risk Factors

Is Dementia Risk Modifiable?

Despite no cure, Alzheimer's incidence is declining by 16% per decade in high-income countries due to advances in managing cardiovascular conditions, reduced smoking, and decreased alcohol consumption. while cases are more common due to growing population , its less frequent

Impact of Risk Factor Reduction

Reducing risk factors can delay dementia onset. A 5% reduction in risk factors could lead to a 6-7% reduction in dementia cases, while a 20% reduction could result in over 30% fewer cases.

Lancet Commission

About 40% of dementia risk factors are potentially modifiable across early, mid, and late life. Early life factors include education, midlife includes hearing loss and late life includes smoking.

Challenges in Studying Modifiable Risk Factors

Influence of risk factors varies by age, and mechanisms are unclear. For instance, obesity is a risk factor in midlife but protective in late life due to frailty. Collecting lifetime data is challenging.

Mechanisms

It's unclear how risk factors like obesity or hearing loss increase dementia risk. Is it through cardiovascular pathways, or other factors such as isolation?

Co-occurrence of Modifiable Risk Factors

Risk factors rarely exist in isolation; they cluster together. Obesity often coincides with physical inactivity, low mood, and poor sleep. This overlap complicates the study of individual risk factors.

Venn Diagram Illustration

Demonstrates overlap across common modifiable risk factor domains (mood, lifestyle, cardiovascular risk factors, sleep, cognitive and social engagement) in middle-aged and older adults.

Unequal Modifiability

Risk factors vary in how easily they can be modified. Some are technically modifiable but difficult at an individual level (e.g., low educational attainment, socioeconomic status, air pollution), while others are more readily modifiable (e.g., hypertension, obesity, physical inactivity).

Barriers and Enablers to Risk Reduction

External enablers include access to healthcare and fresh food. Internal barriers include health literacy, financial resources, social support, and motivation. These factors often cluster together, compounding the complexity.

Impact Variations Across Groups

Impact of risk factors differs by age, ethnicity, and socioeconomic status. The protective effect of education may change in the future due to increased educational attainment.

Lack of Measurement Consensus

There's no consensus on measuring or synthesizing multiple modifiable risk factors. One study used an exposure-wide association study in UK Biobank, synthesizing data into composites like medical history, local environment, and psychosocial feelings.

Theoretical vs. Data-Driven Approaches

Theoretical approaches categorize risk factors into domains (mood, lifestyle, cardiovascular, cognitive/social engagement, sleep). Data-driven approaches use methods like factor analysis to cluster risk factors empirically.

Limitations of Dementia Risk Scores

Common dementia risk scores often include non-modifiable risk factors (age, sex, education), limiting the understanding of other modifiable factors' contributions.

Focus on Cardiovascular Conditions

Most literature focuses on cardiovascular conditions or related behaviors, with fewer studies on multi-domain contributions to cognitive function.

Single Risk Factors Are Complex

Even single risk factors like sleep involve multiple aspects (circadian rhythm dysfunction, obstructive sleep apnea, insomnia). Similarly, depression has different subtypes and associated symptoms.

Lisa's PhD Work

Study Design

Examined theoretically-driven modifiable risk factor domains and cognition in middle-aged adults (40-70 years) from the Healthy Brain Project, looking at domains like mood, lifestyle, cardiovascular conditions, cognitive/social engagement, and sleep disorders.

Key Findings

93% reported at least one modifiable risk factor, with two-thirds reporting risk factors in two or more domains. People with three or more domains showed differences in memory, attention, and subjective cognition.

Individual Risk Domains

Mood and vascular risk factors drove relationships with memory, while mood, sleep, and vascular conditions influenced subjective cognition.

Data-Driven Approach

Factor analysis revealed five dimensions: mood symptoms, cardiovascular conditions, favorable cognitive/social engagements, substance-related lifestyle behaviors, and favorable metabolic health.

Relationships Between Domains and Cognition

In early middle-aged adults, mood symptoms had small relationships with attention and memory, but strong relationships with subjective cognitive concerns. In late middle-aged adults, relationships between mood and cognition were stronger, with some influence from cognitive/social engagement and cardiovascular conditions.

Biomarker Relationships

High modifiable risk factor groups had higher levels of p-tau and total tau (Alzheimer's biomarkers) and poorer cognitive function compared to low-risk groups.

Older Adult Study (ABLE)

Examined older adults from the Australian Imaging Biomarkers and Lifestyle Study, assessing cognition (global, episodic memory, language) and brain volumes (ventricular, white matter, gray matter, hippocampal) over time.

Longitudinal Findings

People with zero modifiable risk factors showed greater cognitive improvement over time. Those with more risk factors showed increased ventricular volume, indicating brain volume loss.

UK Biobank Study

A large study with 350,000 participants and 15 years of follow-up identified associations between modifiable risk factor domains (lifestyle, medical history, local environment, psychosocial factors, physical measures, SES) and dementia outcomes.

Population Attributable Fraction (PAF)

Estimates the proportional reduction in dementia if risk factor exposure were reduced. Shifting unfavorable groups to intermediate could reduce dementia by 47%, while shifting all factors to favorable could reduce it by 72.6%.

Summary

• Modifiable dementia risk factors have varying degrees of modifiability.

• Barriers to engagement exist, even if factors are modifiable.

• Multi-domain risk factors are frequent in middle-aged and older adults.

• Risk factors relate to poorer cognitive performance and less improvement over time.

• Mechanisms may involve complex neurodegenerative processes, including but not limited to those related to Alzheimer's disease.

Future Considerations

• Account for different levels of modifiability.

• Address co-occurrence of risk factors.

• Improve measurement and synthesis of risk factors.

• Account for the dynamic nature of risk factors.

Aging Population and Dementia

Older age is a key risk factor for Alzheimer's, but dementia isn't a normal part of aging. It's due to pathologies like Alzheimer's, cerebrovascular issues, and Lewy body pathology. Once these pathologies are accounted for, the direct correlation between old age and dementia diminishes.

Modifiable Risk Factors

Is Dementia Risk Modifiable?

Despite no cure, Alzheimer's incidence is declining by 16% per decade in high-income countries due to advances in managing cardiovascular conditions, reduced smoking, and decreased alcohol consumption.

Impact of Risk Factor Reduction

Reducing risk factors can delay dementia onset. A 5% reduction in risk factors could lead to a 6-7% reduction in dementia cases, while a 20% reduction could result in over 30% fewer cases.

Lancet Commission

About 40% of dementia risk factors are potentially modifiable across early, mid, and late life. Early life factors include education, midlife includes hearing loss and late life includes smoking.

Challenges in Studying Modifiable Risk Factors

Influence of risk factors varies by age, and mechanisms are unclear. For instance, obesity is a risk factor in midlife but protective in late life due to frailty. Collecting lifetime data is challenging.

Mechanisms

It's unclear how risk factors like obesity or hearing loss increase dementia risk. Is it through cardiovascular pathways, or other factors such as isolation?

Co-occurrence of Modifiable Risk Factors

Risk factors rarely exist in isolation; they cluster together. Obesity often coincides with physical inactivity, low mood, and poor sleep. This overlap complicates the study of individual risk factors.

Venn Diagram Illustration

Demonstrates overlap across common modifiable risk factor domains (mood, lifestyle, cardiovascular risk factors, sleep, cognitive and social engagement) in middle-aged and older adults.

Unequal Modifiability

Risk factors vary in how easily they can be modified. Some are technically modifiable but difficult at an individual level (e.g., low educational attainment, socioeconomic status, air pollution), while others are more readily modifiable (e.g., hypertension, obesity, physical inactivity).

Barriers and Enablers to Risk Reduction

External enablers include access to healthcare and fresh food. Internal barriers include health literacy, financial resources, social support, and motivation. These factors often cluster together, compounding the complexity.

Impact Variations Across Groups

Impact of risk factors differs by age, ethnicity, and socioeconomic status. The protective effect of education may change in the future due to increased educational attainment.

Lack of Measurement Consensus

There's no consensus on measuring or synthesizing multiple modifiable risk factors. One study used an exposure-wide association study in UK Biobank, synthesizing data into composites like medical history, local environment, and psychosocial feelings.

Theoretical vs. Data-Driven Approaches

Theoretical approaches categorize risk factors into domains (mood, lifestyle, cardiovascular, cognitive/social engagement, sleep). Data-driven approaches use methods like factor analysis to cluster risk factors empirically.

Limitations of Dementia Risk Scores

Common dementia risk scores often include non-modifiable risk factors (age, sex, education), limiting the understanding of other modifiable factors' contributions.

Focus on Cardiovascular Conditions

Most literature focuses on cardiovascular conditions or related behaviors, with fewer studies on multi-domain contributions to cognitive function.

Single Risk Factors Are Complex

Even single risk factors like sleep involve multiple aspects (circadian rhythm dysfunction, obstructive sleep apnea, insomnia). Similarly, depression has different subtypes and associated symptoms.

Lisa's PhD Work

Study Design

Examined theoretically-driven modifiable risk factor domains and cognition in middle-aged adults (40-70 years) from the Healthy Brain Project, looking at domains like mood, lifestyle, cardiovascular conditions, cognitive/social engagement, and sleep disorders.

Key Findings

93% reported at least one modifiable risk factor, with two-thirds reporting risk factors in two or more domains. People with three or more domains showed differences in memory, attention, and subjective cognition.

Individual Risk Domains

Mood and vascular risk factors drove relationships with memory, while mood, sleep, and vascular conditions influenced subjective cognition.

Data-Driven Approach

Factor analysis revealed five dimensions: mood symptoms, cardiovascular conditions, favorable cognitive/social engagements, substance-related lifestyle behaviors, and favorable metabolic health.

Relationships Between Domains and Cognition

In early middle-aged adults, mood symptoms had small relationships with attention and memory, but strong relationships with subjective cognitive concerns. In late middle-aged adults, relationships between mood and cognition were stronger, with some influence from cognitive/social engagement and cardiovascular conditions.

Biomarker Relationships

High modifiable risk factor groups had higher levels of p-tau and total tau (Alzheimer's biomarkers) and poorer cognitive function compared to low-risk groups.

Older Adult Study (ABLE)

Examined older adults from the Australian Imaging Biomarkers and Lifestyle Study, assessing cognition (global, episodic memory, language) and brain volumes (ventricular, white matter, gray matter, hippocampal) over time.

Longitudinal Findings

People with zero modifiable risk factors showed greater cognitive improvement over time. Those with more risk factors showed increased ventricular volume, indicating brain volume loss.

UK Biobank Study

A large study with 350,000 participants and 15 years of follow-up identified associations between modifiable risk factor domains (lifestyle, medical history, local environment, psychosocial factors, physical measures, SES) and dementia outcomes.

Population Attributable Fraction (PAF)

Estimates the proportional reduction in dementia if risk factor exposure were reduced. Shifting unfavorable groups to intermediate could reduce dementia by 47%, while shifting all factors to favorable could reduce it by 72.6%.

Summary

• Modifiable dementia risk factors have varying degrees of modifiability.

• Barriers to engagement exist, even if factors are modifiable.

• Multi-domain risk factors are frequent in middle-aged and older adults.

• Risk factors relate to poorer cognitive performance and less improvement over time.

• Mechanisms may involve complex neurodegenerative processes, including but not limited to those related to Alzheimer's disease.

Future Considerations

• Account for different levels of modifiability.

• Address co-occurrence of risk factors.

• Improve measurement and synthesis of risk factors.

• Account for the dynamic nature of risk factors.