Neuroprogression and Cognitive Functioning in Bipolar Disorders

BIPOLAR DISORDERS (W. CORYELL, SECTION EDITOR)

Taiane Cardoso, I. E. Bauer, T. D. Meyer, F. Kapczinski,

J. C. Soares.

Curr Psychiatry Rep (2015) 17: 75 DOI 10.1007/s11920-015-0605-x

VERBAL MEMORY

PSYCHOMOTOR SPEED

EXECUTIVE FUNCTIONING

VISUAL MEMORY

ATTENTION

Eleonora Lombardi PsyD

The pathological reorganization of the

central nervous system along the course of

severe mental disorders. In BD, neural substrate reactivity is changed by

repeated mood episodes, promoting a brain

rewiring that leads to an increased vulnerability to

life stress.



Excluded as included:

children and adolescents. neurological populations. did not use valid pen and

paper or computerized cognitive measures.

no control population. no full text available.

studies that did not include a control group.

Identification: Scopus, Pubmed and OvidMedline database

(n=1229)

Records screened(n =72)

Records after duplicates removed(n =58)

Full-text articles assessed for eligibility

(n =58)

Studies included in the review(n =39)


CHRONICITY Positive association between cognitive decline and poor

clinical outcome in BD.

Number of mood episodes related with slower psychomotor speed on learning and memory tasks verbal memory, attention, cognitive flexibility, and executive functioning.

Illness duration was inversely correlated with verbal, visual memory, psychomotor speed, complex attention, cognitive flexibility, and executive functioning.

Number of hospitalization correlated positively with the degree of impairment in the domains of memory, psychomotor speed, and cognitive processing speed.


AGE OF ONSET

• Pathological early onset: negatively correlated with sustained attention, verbal memory, psychomotor speed, word fluency, and mental flexibility.

• Pathological late onset: a late disease onset was linked to poor performance in the domains of emotion processing, processing speed, and executive functioning compared to early onset BD and HC.


Patients in stage III and IV performed poorly in neuropsychological tests when compared with HC in:

1.executive functions, 2.verbal learning and

memory, 3.working memory,

4.attention.

No significant differences were found in neurocognitive measures between individuals in stage I or

II and HC.Eleonora Lombardi PsyD

ILLNESS COURSE AND COGNITIVE PERFORMANCE:

In BD patients, the executive functioning declined to a greater extent compared with HC.

BD patients with a current mood episode and an illness onset before the age of 25, and found that BD did not differ from HC and SZ in their memory and executive deterioration in over a period of 3 years.


The R. not provide a consistent picture as to whether cognitive decline is associated with illness progression.

The R. reported that decline in executive function and attentional abilities were not related to either illness duration, severity of illness, or number of episodes.

Concluded that there was little to no evidence that deficits in cognitive domains such as psychomotor speed, verbal memory, and executive functions were associated with markers of illness progression in BD.


• Middle-aged patients with BD did not display a more significant cognitive decline in vocabulary, visuo-spatial skills, verbal memory, attention, and executive functions compared to their HC.

• The major limitation of the latter study was, however, the lack of a comparison group such as early-onset BD individuals.

• Two studies on late-onset BD did not find a relationship between cognitive decline, severity of symptoms, and duration illness.


NO CHANGE

5 studies concluded that there was no difference in age-related cognitive decline between BD patients and HC.

Comparison of individuals with BD or MDD and HC (age 18-90) the overall cognitive performance declined at a similar rate in both HC and patients with mood disorders.

Another study investigated the cognitive functioning of middle-aged individuals with BD, SZ, and HC. There was no difference in cognitive decline across groups over time.


NO CHANGE A 12-month longitudinal study in an adult BD did not find

any differences in cognitive decline between BD and HC.

Strejilevich and Martino showed that the performance of older BD patients aged over 40 did not differ from that of younger BD patients and age-matched HC.

Two longitudinal studies with older BD found that the decline in cognitive fields such as inhibition, verbal fluency, and memory progressed at the same speed in BD patients as in age-matched adults.


A naturalistic follow-up study concluded that remitted BD patients on medication experience an improvement in cognitive functioning specifically in processing speed, verbal fluency and memory, and executive functions over time, while those who had experienced psychotic episodes and/or reported substance abuse/dependence may not improve to the same extent as the other participants.


CHANGES 2 studies comparing older BD, MDD, and HC concluded

that older BD displayed poorer processing speed and executive functioning than their HC.

Rej et al. reported that older BD had more deficits in memory, executive functions and processing speed than age-matched HC.

Schouws et al. found that euthymic BD patients display more cognitive deficits than age-matched HC. Given the cross-sectional nature of these studies it is however unknown whether these BD populations presented with cognitive impairment already at a younger age (Tables 1 and 2).


CHANGES

The majority of these studies suggests that in BD cognitive performance may not be affected by brain aging.

Older BD patients who experienced a large number mood episodes may be at higher risk for dementia due to reduced “cognitive reserve”.

In summary, despite some positive findings there is an obvious lack of evidence supporting an age-related longitudinal relationship between cognitive decline and disease progression.


Purpose: …to examinate the

current literature on the relationship between

cognitive deterioration and neuroprogression

in BD.


Evidences:

…cognitive function related to the clinical course of the disease…

1. number of mood episodes,2. hospitalizations, 3. duration of illness.

Cognitive domains: processing speed, verbal memory, and executive functions (e.g.,

planning and inhibition).


Theory of neuroprogression

…increase in the individual’s vulnerability to psychological stress,

brain atrophy, and ultimately cognitive

impairment.


STANGING…

Applied to the pathophysiology of BD

to explain the progressive decline in

mental health, psychosocial

functioning and cognitive performance over the course of the

disease.


ANGING…

The structural brain abnormalities in gray and white matter observed in BD are linked to a process of accelerated brain aging…

Increased inflammation may lead to neuronal loss in gray and white matter brain regions similar to that

observed in age-related neurodegenerative diseases such as dementia.


Higher levels of pro-inflammatory cytokines plays a role in the progressive cognitive and neuroanatomical changes

observed during the course of BD.

?absence of physiological measures of

inflammation or stress that could confirm the role of neuroprogression in cognitive

impairment … WHY?


Unclear definition of “euthymia” and “remission”.

Additional large scale cross-sequential studies to determine the role of neurotoxic processes associated with the BD on brain function and cognitive abilities.

Problematic self-report.

Drugs effects on cognitive function.


Science

Neuroprogression and Cognitive Functioning in Bipolar Disorders