Happiness, defined as an overall appreciation for one's life, is being increasingly shown to afford several protective health benefits. Happier individuals tend to have a greater life expectancy, enjoy better physical health, and possess greater psychological resilience.
Early studies have shown that higher emotional while being, is a key marker associated with reduced mortality even after controlling for physical, social, and cognitive functioning. Consequently, an examination of the mental on social factors that are commonly associated with cognitive impairment is becoming increasingly able to inform the relationship between cognitive impairment such as dementia and happiness.
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The impact of early-life happiness in the development of dementia
One of the most recent studies that suggest that happiness in early adulthood may protect against dementia comes from the University of California, San Francisco (UCSF) and was published in September 2021. This builds on an existing body of evidence that shows a correlation between depression and dementia; while many of these studies have pointed to the prevalence of depression in later life, this research demonstrates that depression in early adulthood could lead to lower cognition over a decade later, as well as cognitive decline in older age.
In this research, statistical methods were applied to predict average trajectories of depressive symptoms for ~15,000 participants between the ages of 20 and 89 who were divided into 3 stages of life. These included older, midlife, and young adulthood. These predicted trajectories showed that the likelihood of cognitive impairment in the group of older participants was 73% greater for those assessed as having elevated depressive symptoms in early adulthood, and 43% higher for those with elevated depressive symptoms presented later in life.
These results were adjusted for several parameters including sex, race, age, body mass index, educational attainment coma smoking status, and history of diabetes. Where depressive symptoms were experienced in midlife, the association with cognitive impairment was discounted when adjusting for depression in other life stages.
Life stage, depression and dementia
The results of this most recent study together with an existing body of research show an association between depression and dementia that implies that the timing of depression is important to define the nature of the association.
Specifically, depression in earlier life or depressive symptoms are associated with approximately a 2-fold or more increase in the risk of dementia. Contrastingly, common studies of mid-and late-life depression show a less robust link.
Depressive symptom trajectories fit a U-shaped curve, which is similar to other age-related trends. In general, the greater the severity of depressive symptoms, the lower the cognition, and faster rates of decline are seen. This is particularly true when moderate or high depressive symptoms presented in early adulthood are observed – this results in a drop in cognition over a decade.
Potential mechanisms that link depression with the development of dementia
The most prominent mechanisms that suggest that depression plays a causative role in the development of dementia are varied, however, each represents a mechanistic link between depression-related processes is and dementias-specific neuropathology.
Overall, depression is thought to alter glucocorticoids which subsequently results in hippocampal atrophy (wasting), and increased deposition of beta-amyloid plaques, changes in inflammation, and deficits in nerve growths or neurotrophins. The hippocampus is implicated in learning and memory.
Among them, vascular disease presents the strongest evidence linking depression and dementia. This link is grounded in what is known as the vascular depression hypothesis.
This suggests that cerebral vascular diseases predispose, perpetuate, or precipitate individuals’ development of later-life depressive syndromes. Several studies have demonstrated that vascular lesions and structural brain changes may contribute to depression in later life.
Whether a vascular disease or vascular lesions result in depression or result from depression remains to be determined as both are associated with an increased risk of developing one another.
Ultimately, the pathway from vascular disease to depression is likely unlikely to be sequential. Depression is related to the development of vascular disease through multiple mechanisms including changes in behavior (i.e., smoking and inactivity), hypothalamic-pituitary-adrenal (HPA) axis dysregulation and elevated cortisol, endothelial function disruption, development of hypertension, and pro-inflammatory cytokines.
Likewise, vascular disease can cause damage to brain regions that control executive function, psychomotor slowing, and promote resistance to treatment common in late-life depression.
This growing body of literature suggests that patients presenting with early or late-life depression or depressive symptoms should be screened and monitored for cognitive deficits, including depression over time.
This is especially salient as the risk of dementia is projected to quadruple by 2050, therefore intervening on a modifiable risk factor such as depression, and continuing to monitor its effects on the risk, is imperative. The mechanistic pathway that links depression to dementia is multifactorial and non-linear, suggesting that treatment approaches should be equally as multifaceted.
This adds to a growing list of reasons why the screening and treatment of depression are important.
References:
- Brenowitz WD, Al Hazzouri AZ, Vittinghoff E, et al. (2021) Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline. J Alz Dis. doi:10.3233/JAD-210588.
- Byers AL, Yaffe K. Depression, and risk of developing dementia. (2011) Nat Rev Neurol. doi:10.1038/nrneurol.2011.60.
- Ouanes S, Popp J.(2019) High Cortisol and the Risk of Dementia and Alzheimer's Disease: A Review of the Literature. Front Aging Neurosci. doi:10.3389/fnagi.2019.00043.
- Green RC, Cupples LA, Kurz A, et al. (2003) Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol. doi:10.1001/archneur.60.5.753.
- Almeida OP, Hankey GJ, Yeap BB, et al. (2017) Depression as a modifiable factor to decrease the risk of dementia. Transl Psychiatry. doi:10.1038/tp.2017.90.
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