Hopelessness as Risk Factor for Alzheimer's Disease

Original figure from Hakansson K et al. (citation below)

I have been reviewing advances in neuropsychology in neuroscience medicine.

One important relevant topic is the art of neuropsychological testing for the early diagnosis and monitoring of Alzheimer's and other dementias.

Another important focus is finding neuropsychological risk factors for later development of cognitive impairment.

Mid-life depression has been identified as a risk factor for later life cognitive impairment and Alzheimer's disease. The exact mechanism for this association is unclear. 

A recent study from a cohort in Finland (CAIDE study--Cardiovascular risk factors, aging and dementia study) identified midlife levels of hopelessness with later risk of cognitive impairment and dementia.

Subjects in this study were interviewed between the ages of 39 and 64 years and then re-interviewed an average of 20 years later.

Midlife hopeless was rated on a five point scale for two questions in the study:

• "I feel that it is impossible to reach the goals I would like to strive for"
• "The future seems to be hopeless, and I can't believe that things are changing for the better"

Subjects second later assessments included a screen for cognitive impairment (Mini-mental status examination-MMSE). Those screening positive for cognitive impairment underwent additional neuropsychological assessment including DSM-IV diagnostic assessment for Alzheimer's disease. Subjects also underwent brain MRI testing to rule out vascular dementia. Additionally, participants had genetic testing for the presence of the Alzheimer's genotype risk factor ApoE4.

The key findings from the study included:

• There was a 30% increase in cognitive impairment risk for each level of increase in hopelessness rating at midlife 
• There was a 37% increase in Alzheimer's disease risk for each level of increase in hopelessness rating at midlife
• Hopelessness increased Alzheimers disease risk in both those with and without the ApoE4 Alzheimer's risk genotype
• Those with both the ApoE4 risk genotype and high levels of hopelessness had the greatest increase in later risk for Alzheimer's disease--sixfold increase (see chart)

It is possible that the baseline hopelessness assessment score was simply a proxy for depression. Unfortunately the study did not include a comprehensive baseline depression assessment to tease out this relationship.

The authors note their study may show a relatively simple approach to identifying a midlife neuropsychological risk factor for Alzheimer's disease.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.

Chart is an original figure from the manuscript reproduced here under the terms of the Creative Commons Attribution License.

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Håkansson K, Soininen H, Winblad B, & Kivipelto M (2015). Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study. PloS one, 10 (10) PMID: 26460971