Psychiatric symptoms speed up Alzheimer’s progression

People with dementia and their care partners - Photo by: K. Kendall

Two recent studies published in the American Journal of Geriatric Psychiatry found evidence of a possible association between Neuropsychiatric symptoms (NPS) and a faster progression towards Dementia and Alzheimer’s Disease (AD). The two studies published on February analyzed the progression of two patient cohorts affected by mild cognitive impairment (MCI) to more severe forms of dementia, including AD. In the first study led by Dr. Scott Mackin, patients with MCI who suffered from chronic depression showed more rapid rates of conversion from MCI to AD. The evidence found suggested that this psychiatric condition may contribute to a faster conversion due to unique brain changes. The data from the second study, led by Dr. Sarah Forrseter at Johns Hopkins University, Baltimore, highlighted how patients included in some NPS clusters progressed to AD and dementia in a shorter timespan. The studies may help clinicians and specialists in pinpointing who the patients are that should be overlooked more carefully because of their higher risk of cognitive decline.


Depression and Alzheimer’s Disease progression

Dr. Mackin’s study investigated the effects of chronic depression and brain atrophy in the conversion from MCI to AD and dementia. He and his colleagues from the University of California, San Francisco, selected 94 MCI elderly patients from the Alzheimer’s Disease Neuroimaging Initiative repository. Among these subjects, 32 showed symptoms of chronic depression, which were associated with a more rapid anterior cingulate and frontal lobe atrophy. Both these cortical regions are known to be involved in AD progression. During a subsequent 3-years follow-up, in 38 patients (42.7%) MCI increased to AD. However, those who showed signs of chronic depression showed an almost doubled incidence of AD (62.1% vs. 33.3%). The time for MCI to be converted into AD was 60% shorter in patients with chronic depressive symptoms than in those without (P = .008).

The researchers suggested that the progressive atrophy of the frontal brain regions associated with chronic depression symptoms might be considered as an additional risk factor for AD itself, instead of just a prodromal symptom of incident dementia. Although the study proves a possible association between affective symptoms and AD risk, it’s still possible that those symptoms, as well as dementia, could be caused by the underlying neurodegenerative changes of this condition.


Neuropsychiatric symptoms and progression to Dementia

The other study led by Dr. Forrester and colleagues investigated progression to AD in 540 subjects affected by MCI taken from the Alzheimer’s Disease Cooperative Study (ADCS). Patients were assessed with the Neuropsychiatric Inventory Questionnaire during a follow-up period of 2 years. Subjects were further divided into subgroups depending on whether they manifested neuropsychiatric symptoms. These subgroups were included in three NPS clusters: a first, most severe one (with a 7% prevalence) defined by high rates of disinhibition (44%), anxiety (52%), nighttime behaviors (48%), agitation (84%), and apathy (51%); an affective cluster (with a 37% prevalence) described by superior rates of irritability (32%), nighttime behaviors (35%), depression (41%), and anxiety (31%); and a third asymptomatic cluster (with a 56% prevalence) where no more than 5% of the patients showed any symptom.

In the follow-up period, 78% of the patients (419) showed no signs of MCI progression, 22% (121 patients) progressed to dementia or AD, and 31% (167) reverted to normal cognition. However, the cluster where NPS symptoms were severe, showed a two-fold higher risk of progression to dementia than the asymptomatic one (hazard ratio [HR] = 2.69), while the affective cluster showed an over 1.5 times higher risk (HR = 1.79). The researchers highlighted how a potential classification of the patients based on their NPS, could help physicians understand the progression of AD and dementia as soon as these symptoms manifest themselves. Also, precocious identification of NPS may help prevent the risk of MCI and dementia in specific patient populations.

Taken together, the two studies may help future researchers understand whether a causal relationship actually exists between NPS (including depression) and AD and dementia risk. Still, although further researches are required to better understand this relationship, alleviating affective symptoms as early as possible may still be useful to reduce the risk of dementia in selected individuals.




Article written by Dr. Claudio Butticè, PharmD.



  1. Forrester, Sarah N. et al. Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia. The American Journal of Geriatric Psychiatry, Volume 24, Issue 2, 117 – 125
  2. Sacuiu, Simona et al. Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia. The American Journal of Geriatric Psychiatry, Volume 24, Issue 2, 126 – 135
  3. Psychiatric Symptoms Speed Conversion to Dementia. Medscape. Feb 29, 2016.