What tools exist to assess the presence of multiple risk factors for dementia in middle-aged people, and can they correctly predict future dementia?

Key messages

• We found 14 tools used in middle-aged people to predict future dementia. 

• Seven studies tested a prediction tool named Cardiovascular Risk Factors, Ageing, and Dementia (CAIDE). 

• The benefits of using these tools to predict dementia later in life are unclear, because the studies provided little high-quality evidence.

What is dementia? 

Dementia refers to a group of brain conditions that commonly affect older people and lead to progressive problems with memory, problem-solving, or performing everyday activities. People with certain health conditions or behaviours in middle age – such as high blood pressure, excessive alcohol intake, smoking, depression, low levels of exercise, or poor diet – have a higher chance of developing dementia in later life. We classify these health conditions or behaviours as 'modifiable risk factors' for dementia, because measures such as lifestyle changes can reduce them.

What are prediction tools? 

To develop prediction tools, researchers observe a group of people over years to see how many with such risk factors develop dementia. The tools assign a higher risk score to people who have a higher chance of getting dementia later in life, based on the presence or absence of risk factors in middle age.

Why do we use tools that assess risk factors to predict future dementia?

Currently, about 50 million people across the world have dementia, and without adequate preventive measures, that number is expected to triple by 2050. If we control risk factors in middle age, we may avert or delay the future development of dementia or reduce dementia severity. Preventive tools help select people who are best suited to lifestyle modification programmes aimed at regulating risk factors. 

What did we want to find out?

We wanted to find out what tools are available for middle-aged adults (aged 45 to 65 years), and how well they predict dementia later in life (at least five years after the initial assessment). We looked for tools that included risk factors widely accepted to be linked to dementia onset.

What did we do? 

We searched for studies that evaluated tools used in middle-aged adults to identify those at high risk of dementia later in life. We investigated how well these tools predicted future dementia based on an accuracy value. If the accuracy value is more than a recommended standard of 0.75, we can say that the tool is accurate at predicting future dementia. It is also important to establish that a tool developed in one group of people (in the original development study) can accurately predict dementia in another group of people (in validation studies); only then can it be applied in routine healthcare practice. We compared and summarised the results of the studies.

What did we find?

We found 20 studies that described 14 different tools for dementia prediction. The tools included between two and 11 modifiable risk factors for dementia. Seven of the tools featured in two or more studies and were considered validated. Seven studies used a tool called Cardiovascular Risk Factors, Ageing, and Dementia (CAIDE). The CAIDE tool included current measures of a person's blood pressure, weight and height, cholesterol level, and frequency of exercise to predict future dementia. The combined accuracy value across the studies was 0.71, not high enough for us to consider CAIDE a reliable tool for predicting future dementia. 

What are the limitations of the evidence?

Half (seven) of the tools were used in a single study, so we were unable to measure how well they predicted future dementia. Most studies provided too little information for us to assess accuracy values.

How up to date is this evidence?

The evidence is up-to-date to June 2022.

Authors' conclusions: 

We identified 14 unique multi-domain prognostic models used in middle-aged adults for predicting subsequent dementia. Diabetes, hypertension, obesity, and smoking were the most common modifiable risk factors used as predictors in the models. We performed meta-analyses of C-statistics for one model (CAIDE), but the summary values were unreliable. Owing to lack of data, we were unable to meta-analyse the calibration measures of CAIDE. This review highlights the need for further robust external validations of multi-domain prognostic models for predicting future risk of dementia in middle-aged adults.

Read the full abstract...

Dementia, a global health priority, has no current cure. Around 50 million people worldwide currently live with dementia, and this number is expected to treble by 2050. Some health conditions and lifestyle behaviours can increase or decrease the risk of dementia and are known as 'predictors'. Prognostic models combine such predictors to measure the risk of future dementia. Models that can accurately predict future dementia would help clinicians select high-risk adults in middle age and implement targeted risk reduction.


Our primary objective was to identify multi-domain prognostic models used in middle-aged adults (aged 45 to 65 years) for predicting dementia or cognitive impairment. Eligible multi-domain prognostic models involved two or more of the modifiable dementia predictors identified in a 2020 Lancet Commission report and a 2019 World Health Organization (WHO) report (less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, diabetes mellitus, air pollution, poor diet, and cognitive inactivity). Our secondary objectives were to summarise the prognostic models, to appraise their predictive accuracy (discrimination and calibration) as reported in the development and validation studies, and to identify the implications of using dementia prognostic models for the management of people at a higher risk for future dementia.

Search strategy: 

We searched MEDLINE, Embase, PsycINFO, CINAHL, and ISI Web of Science Core Collection from inception until 6 June 2022. We performed forwards and backwards citation tracking of included studies using the Web of Science platform. 

Selection criteria: 

We included development and validation studies of multi-domain prognostic models. The minimum eligible follow-up was five years. Our primary outcome was an incident clinical diagnosis of dementia based on validated diagnostic criteria, and our secondary outcome was dementia or cognitive impairment determined by any other method.

Data collection and analysis: 

Two review authors independently screened the references, extracted data using a template based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS), and assessed risk of bias and applicability of included studies using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). We synthesised the C-statistics of models that had been externally validated in at least three comparable studies. 

Main results: 

We identified 20 eligible studies; eight were development studies and 12 were validation studies. There were 14 unique prognostic models: seven models with validation studies and seven models with development-only studies. The models included a median of nine predictors (range 6 to 34); the median number of modifiable predictors was five (range 2 to 11). The most common modifiable predictors in externally validated models were diabetes, hypertension, smoking, physical activity, and obesity. In development-only models, the most common modifiable predictors were obesity, diabetes, hypertension, and smoking. No models included hearing loss or air pollution as predictors. Nineteen studies had a high risk of bias according to the PROBAST assessment, mainly because of inappropriate analysis methods, particularly lack of reported calibration measures. Applicability concerns were low for 12 studies, as their population, predictors, and outcomes were consistent with those of interest for this review. Applicability concerns were high for nine studies, as they lacked baseline cognitive screening or excluded an age group within the range of 45 to 65 years.

Only one model, Cardiovascular Risk Factors, Ageing, and Dementia (CAIDE), had been externally validated in multiple studies, allowing for meta-analysis. The CAIDE model included eight predictors (four modifiable predictors): age, education, sex, systolic blood pressure, body mass index (BMI), total cholesterol, physical activity and APOEƐ4 status. Overall, our confidence in the prediction accuracy of CAIDE was very low; our main reasons for downgrading the certainty of the evidence were high risk of bias across all the studies, high concern of applicability, non-overlapping confidence intervals (CIs), and a high degree of heterogeneity.

The summary C-statistic was 0.71 (95% CI 0.66 to 0.76; 3 studies; very low-certainty evidence) for the incident clinical diagnosis of dementia, and 0.67 (95% CI 0.61 to 0.73; 3 studies; very low-certainty evidence) for dementia or cognitive impairment based on cognitive scores. Meta-analysis of calibration measures was not possible, as few studies provided these data.