# Brain

Source: https://synapse-lifestyle.com/en/reference-guide/brain

## Overstimulation

Synapse uses the GAD-7 questionnaire to assess the level of overstimulation in patients. This questionnaire was originally designed to detect generalised anxiety disorder in primary care, but since generalised anxiety disorder often stems from autonomic dysregulation[1, 2], Synapse frames this as overstimulation — a concept that more accurately reflects the underlying physiology.

The score categories[3] used by Synapse are:

| GAD-7 Score |  |
| --- | --- |
| No overstimulation | ≤4 |
| Mild overstimulation | 5-9 |
| Moderate overstimulation | 10-14 |
| Marked overstimulation | >14 |

## Brain health

Brain health in Synapse is assessed using the McCance Brain Care Score[4] (BCS), a concise yet powerful questionnaire that maps thirteen known risk factors. Large clinical databases show that this score helps predict dementia and stroke, and it has been validated against neurological abnormalities detected on brain imaging[5].

The McCance Brain Care Score focuses on 12 domains across three main areas:

1. Physical factors (blood pressure, blood glucose, cholesterol, BMI)
2. Lifestyle (nutrition, alcohol use, smoking, aerobic activity, sleep)
3. Psychosocial (stress management, social relationships, sense of purpose)

For each of these 12 topics, patients are given multiple response options. The individual scores are summed to give a total, with 23 being the highest possible score. Higher scores indicate better brain health. At Synapse, we use the following cut-off values.

| Brain health | McCance Brain Care Score |
| --- | --- |
| Optimal | ≥17 |
| Acceptable | 14-16 |
| Under strain | 11-13 |
| At risk | ≤10 |

### Physical factors

### Blood pressure

There is growing evidence that high blood pressure (hypertension) is the most important modifiable vascular risk factor for both the onset and progression of cognitive decline and dementia[6]. Elevated blood pressure accelerates vascular disease in both large and small cerebral vessels, which can lead to infarcts, haemorrhages, and white matter lesions. This is partly due to reduced cerebrovascular reserve and degenerative changes in the vessel wall.

We have adapted the McCance Brain Care Score for blood pressure as follows:

| Blood pressure | Score |
| --- | --- |
| >140 or >95 mmHg | 0 |
| >135 or >90 mmHg | 1 |
| >130 or >85 mmHg | 2 |
| ≤130 and ≤85 mmHg | 3 |

#### Hemoglobin A1C

##### HbA1c

HbA1c (glycated haemoglobin) reflects the average blood glucose concentration over the preceding two to three months: the higher the average glucose level, the greater the proportion of HbA1c. Elevated blood glucose contributes to the formation of advanced glycation end-products (AGEs), which cause oxidative damage, inflammatory responses, and can promote dyslipidaemia — all mechanisms that impair cognitive function and can lead to brain damage[7].

In the McCance Brain Care Score, HbA1c is scored as follows:

| HbA1c | McCance Brain Care Score |
| --- | --- |
| ≥6.5% | 0 |
| 5.7 - 6.5% | 1 |
| <5.7% | 2 |

##### Hyperglycaemia

When no HbA1c value is available, Synapse uses fasting glucose as a substitute. Following the scoring mechanism used by the Brain Care Score for HbA1c, fasting glucose is assessed as follows:

| Fasting glucose | McCance Brain Care Score |
| --- | --- |
| >125mg/dL | 0 |
| 100-125mg/dL | 1 |
| ≤99mg/dL | 2 |

#### Cholesterol

High cholesterol in middle age increases the risk of cognitive decline and dementia in later life[8]. One possible explanation is that excess cholesterol contributes to atherosclerosis, which can reduce the efficiency of blood flow to the brain. This can result in small or larger areas of brain tissue damage, with cognitive decline as a consequence.

In the McCance Brain Care Score, cholesterol level is assessed as follows:

| Total cholesterol | McCance Brain Care Score |
| --- | --- |
| ≥190mg/dL or on treatment | 0 |
| <190mg/dL | 1 |

#### BMI

Sustained high BMI can negatively affect the brain through the associated cardiometabolic consequences — such as vascular problems, insulin resistance, and chronic inflammation. This can manifest as reduced brain volume, changes in white matter structure, and more white matter lesions[9].

In the McCance Brain Care Score, BMI is assessed as follows:

| BMI | McCance Brain Care Score |
| --- | --- |
| ≥30kg/m^2 | 0 |
| 25-30kg/m^2 | 1 |
| 18.5-25kg/m^2 | 2 |
| <18.5kg/m^2 | 1 |

### Lifestyle

#### Nutrition

A diet rich in fibre and high-quality protein, with limited intake of refined sugars and processed foods and sufficient healthy fats, is essential for optimal brain function[10, 11]. A dietary pattern consisting mainly of sugary or highly processed foods can, by contrast, lead to chronic inflammation, insulin resistance, and an increased risk of neurodegenerative disease.

In the McCance Brain Care Score, dietary pattern is assessed as follows:

| Typical weekly diet | McCance Brain Care Score |
| --- | --- |
| Does not meet the above recommendations | 0 |
| Partially meets the recommendations | 1 |
| Meets the recommendations | 2 |

#### Alcohol

Alcohol consumption can cause neuronal death and has a direct impact on brain structure[12]. Key mechanisms include exposure to acetaldehyde, increased oxidative stress, and impaired glucose metabolism following acute alcohol intake.

In addition, liver damage can allow harmful substances — normally broken down in the liver — to reach the brain. It has also been shown that excessive alcohol use can reduce stem cell numbers, impairing the formation of new neurons.

In the McCance Brain Care Score, alcohol use is assessed as follows:

| Alcoholic drinks | McCance Brain Care Score |
| --- | --- |
| >4 per week | 0 |
| 3-4 per week | 1 |
| 0-2 per week | 2 |

The colour and verdict of this row come from the alcohol lifestyle score, the same as on the lifestyle sheet; the points above count towards the brain score.

#### Smoking

Tobacco smoke and tobacco products contain thousands of harmful substances, including nicotine. Many of these components are toxic to the nervous system, the cardiovascular system, and the lungs[13]. Smoking therefore increases the risk not only of cardiovascular disease but also of cognitive decline and other neurological conditions.

In the McCance Brain Care Score, smoking behaviour is assessed as follows:

| Smoking | McCance Brain Care Score |
| --- | --- |
| Current smoker | 0 |
| Never smoked or quit more than a year ago | 3 |

#### Exercise

Physical activity (PA), defined as any movement generated by skeletal muscles that results in energy expenditure, is one of the most promising strategies for supporting cognitive function throughout life and reducing the risk of age-related cognitive decline[14].

In the McCance Brain Care Score, physical exercise is assessed as follows:

| Physical exercise | McCance BCS |
| --- | --- |
| <150 min/week moderate and <75 min/week vigorous | 0 |
| ≥150 min/week moderate or ≥75 min/week vigorous | 3 |

##### Moderate exercise

Moderate forms of exercise have proven beneficial effects on the brain[15]. A key mechanism is increased production of brain-derived neurotrophic factor (BDNF), a protein that stimulates neuroplasticity and neurogenesis in the hippocampus. Cardiorespiratory exercise also contributes to improved blood flow to brain tissue, helping to maintain and enhance cognitive function.

##### Vigorous exercise

For those with less time or who prefer shorter, more intense training, interval or high-intensity exercise can serve as an efficient substitute for longer moderate endurance training. This form of exercise produces similar cardiovascular adaptations and is associated with better cardiorespiratory fitness, which in turn correlates with more favourable cognitive performance[16].

#### Sleep

Good sleep is essential for brain health. Epidemiological research shows that sleep deprivation or untreated sleep disorders are associated with an increased risk of cognitive decline and other neurological problems[17]. Sleep supports the regulation of metabolic processes and the clearance of waste products from the brain, meaning that disrupted or insufficient sleep can place additional strain on the brain.

Synapse assesses your sleep using two complementary self-report questionnaires. The MSQ maps your sleep-wake pattern: what happens during the night and during the day. The ISI (Insomnia Severity Index) measures your experience: how much it bothers you and how much it affects your daytime functioning. That is why we show two factors per sleep domain: a pattern factor (from the MSQ) and an experience factor (from the ISI). This way you can see both what is going on and how heavily it weighs.

The experience factors are colour-coded according to the ISI thresholds: for Insomnia, the boundary between green and orange sits around a score that corresponds to clinical insomnia, so an orange colour gives you a clear signal — even when your average sleep figure still looks mild.

In the McCance Brain Care Score, sleep is assessed as follows:

| Sleep | BCS |
| --- | --- |
| Untreated sleep disorders and/or fewer than 7 hours per night | 0 |
| Treated sleep disorders and 7–8 hours per night | 1 |

### Psychosocial

#### Stress

Prolonged overstimulation of the stress system repeatedly activates the HPA axis, causing glucocorticoids to damage the hippocampus, prefrontal cortex, and amygdala over time. This leads to changes in synaptic plasticity, neurogenesis, and the dendritic structure of the brain, resulting in neurodegeneration with measurable consequences for cognition, mood, and overall brain health[18].

In the McCance Brain Care Score, stress is assessed as follows:

| Stress | BCS |
| --- | --- |
| High stress level with impact on functioning | 0 |
| Moderate stress level with limited impact on functioning | 1 |
| Normal stress level | 2 |

#### Loneliness

Lack of social connectedness weakens the immune system, increases susceptibility to infections, and is associated with structural changes in brain regions such as the prefrontal cortex, insula, amygdala, and hippocampus[19]. These neural adaptations are linked to cognitive decline and mood disorders.

In the McCance Brain Care Score, loneliness is assessed as follows:

| Loneliness | BCS |
| --- | --- |
| No or very few close contacts | 0 |
| At least two trusted people outside partner/children | 1 |

#### Wellbeing

A strong sense of purpose and life satisfaction is associated with greater grey matter volume and higher activity in the anterior cingulate and orbitofrontal cortex. These areas regulate emotions and process meaningful stimuli, reducing stress and increasing cognitive resilience. A high level of wellbeing therefore demonstrably contributes to better brain health[20].

In the McCance Brain Care Score, wellbeing is assessed as follows:

| Wellbeing | BCS |
| --- | --- |
| Regularly struggles to see value or purpose in life | 0 |
| Usually has a clear sense of meaning and purpose | 1 |

## Mood and burnout

### Burnout

The WHO describes burnout in ICD-11 (QD85) as an occupational phenomenon, not a medical condition, resulting from chronic work stress with three features: exhaustion, mental distance or cynicism towards work, and reduced efficacy. Burnout and depression are clearly related but are not identical constructs[21]. Prospective studies link burnout to type 2 diabetes, coronary heart disease, hypercholesterolaemia, insomnia, depressive symptoms and absenteeism[22].

Synapse derives the factor from a single question on the degree of burning out; it turns orange when someone is starting to burn out or only just holding on, and red when someone is burnt out or seeking help. A single question correlates only moderately with the full Maslach Burnout Inventory[23] and, in comparative studies, misses part of those who score high on the full scale[24]. A positive signal is therefore a reason for a conversation: rule out depression and suicidal thoughts, check physical causes of exhaustion, and combine recovery with adjustments at work. Work-directed interventions improved return to work in employees with burnout[25].

Developed and reviewed with the Synapse [medical advisory board](https://synapse-lifestyle.com/en/advisory-board).

## References

1. Owens, A. P., Low, D. A., Iodice, V., Critchley, H. D. & Mathias, C. J. The genesis and presentation of anxiety in disorders of autonomic overexcitation. Autonomic Neuroscience 203, 81–87 (2017). https://doi.org/10.1016/j.autneu.2016.10.004
2. Jordan, P., Shedden-Mora, M. C. & Löwe, B. Psychometric analysis of the Generalized Anxiety Disorder scale (GAD-7) in primary care using modern item response theory. PLoS One 12, e0182162 (2017). https://doi.org/10.1371/journal.pone.0182162
3. Plummer, F., Manea, L., Trepel, D. & McMillan, D. Screening for anxiety disorders with the GAD-7 and GAD-2: a systematic review and diagnostic metaanalysis. Gen Hosp Psychiatry 39, 24–31 (2016). https://doi.org/10.1016/j.genhosppsych.2015.11.005
4. Singh, S. D. et al. The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort. Front Neurol 14, (2023). https://doi.org/10.3389/fneur.2023.1291020
5. Rivier, C. A. et al. Brain Care Score and Neuroimaging Markers of Brain Health in Asymptomatic Middle-Age Persons. Neurology 103, (2024). https://doi.org/10.1212/WNL.0000000000209687
6. Gąsecki, D., Kwarciany, M., Nyka, W. & Narkiewicz, K. Hypertension, Brain Damage and Cognitive Decline. Curr Hypertens Rep 15, 547–558 (2013). https://doi.org/10.1007/s11906-013-0398-4
7. Tian, C. et al. The causal effect of HbA1c on white matter brain aging by two-sample Mendelian randomization analysis. Front Neurosci 17, (2024). https://doi.org/10.3389/fnins.2023.1335500
8. van Vliet, P. Cholesterol and Late-Life Cognitive Decline. Journal of Alzheimer’s Disease 30, S147–S162 (2012). https://doi.org/10.3233/JAD-2011-111028
9. Lv, H. et al. Association between Body Mass Index and Brain Health in Adults: A 16- Year Population-Based Cohort and Mendelian Randomization Study. Health Data Science 4, (2024). https://doi.org/10.34133/hds.0087
10. Smith, P. J. & Blumenthal, J. A. DIETARY FACTORS AND COGNITIVE DECLINE. J Prev Alzheimers Dis 1–12 (2015) https://doi.org/10.14283/jpad.2015.71
11. Spencer, S. J., Korosi, A., Layé, S., Shukitt-Hale, B. & Barrientos, R. M. Food for thought: how nutrition impacts cognition and emotion. NPJ Sci Food 1, 7 (2017). https://doi.org/10.1038/s41538-017-0008-y
12. Karoly, H. C., Kirk‐Provencher, K. T., Schacht, J. P. & Gowin, J. L. Alcohol and brain structure across the lifespan: A systematic review of large‐scale neuroimaging studies. Addiction Biology 29, (2024). https://doi.org/10.1111/adb.13439
13. Swan, G. E. & Lessov-Schlaggar, C. N. The Effects of Tobacco Smoke and Nicotine on Cognition and the Brain. Neuropsychol Rev 17, 259–273 (2007). https://doi.org/10.1007/s11065-007-9035-9
14. ERICKSON, K. I. et al. Physical Activity, Cognition, and Brain Outcomes: A Review of the 2018 Physical Activity Guidelines. Med Sci Sports Exerc 51, 1242–1251 (2019). https://doi.org/10.1249/MSS.0000000000001936
15. Olson, R. L., Cleveland, D. J. & Materia, M. Effects of Low-Intensity Aerobic Exercise on Neurophysiological and Behavioral Correlates of Cognitive Function. Behavioral Sciences 13, 401 (2023). https://doi.org/10.3390/bs13050401
16. Liu, K. et al. The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis. Sci Rep 14, 32082 (2024). https://doi.org/10.1038/s41598-024-83802-9
17. Gottesman, R. F. et al. Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association. Stroke 55, (2024). https://doi.org/10.1161/STR.0000000000000453
18. McManus, E., Haroon, H., Duncan, N. W., Elliott, R. & Muhlert, N. The effects of stress across the lifespan on the brain, cognition and mental health: A UK biobank study. Neurobiol Stress 18, 100447 (2022). https://doi.org/10.1016/j.ynstr.2022.100447
19. Hawkley, L. C. Loneliness and health. Nat Rev Dis Primers 8, 22 (2022). https://doi.org/10.1038/s41572-022-00355-9
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22. Salvagioni, D. A. J. et al. Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies. PLoS One 12, e0185781 (2017). https://doi.org/10.1371/journal.pone.0185781
23. Hagan, G., Okut, H. & Badgett, R. G. A Systematic Review of the Single-Item Burnout Question: Its Reliability Depends on Your Purpose. J Gen Intern Med 39, 818–828 (2024). https://doi.org/10.1007/s11606-024-08685-y
24. Knox, M. et al. Maslach Burnout Inventory and a self-defined, single-item burnout measure produce different clinician and staff burnout estimates. J Gen Intern Med 33, 1344–1351 (2018). https://doi.org/10.1007/s11606-018-4507-6
25. Lambreghts, C. et al. Return-to-work interventions for sick-listed employees with burnout: a systematic review. Occup Environ Med 80, 538–544 (2023). https://doi.org/10.1136/oemed-2023-108867