Depressive Symptoms in Mild Cognitive Impairment Predict Greater Atrophy in Alzheimer's Disease-Related Regions

Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, USA.
Biological psychiatry (Impact Factor: 10.26). 02/2012; 71(9):814-21. DOI: 10.1016/j.biopsych.2011.12.024
Source: PubMed


Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI.
Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups.
Depressed subjects had more frontal (p = .024), parietal (p = .030), and temporal (p = .038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy.
Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.

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    • "There is only a 30% chance that someone with SMC has MCI [16]. It is common that patients with brain atrophy not only have MCI but also have neuropsychiatric symptoms [17]. The common core non-cognitive symptoms in MCI patients are anxiety [18] [19] and sleep disorder [20] [21]. "
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    ABSTRACT: Background: Cognitive impairment is a major problem in elderly, affecting quality of life. Pre-clinical studies show that MMFS-01, a synapse density enhancer, is effective at reversing cognitive decline in aging rodents. Objective: Since brain atrophy during aging is strongly associated with both cognitive decline and sleep disorder, we evaluated the efficacy of MMFS-01 in its ability to reverse cognitive impairment and improve sleep. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-designed trial in elderly subjects (age 50-70) with cognitive impairment. Subjects were treated with MMFS-01 (n = 23) or placebo (n = 21) for 12 weeks and cognitive ability, sleep quality, and emotion were evaluated. Overall cognitive ability was determined by a composite score of tests in four major cognitive domains. Results: With MMFS-01 treatment, overall cognitive ability improved significantly relative to placebo (p = 0.003; Cohen's d = 0.91). Cognitive fluctuation was also reduced. The study population had more severe executive function deficits than age-matched controls from normative data and MMFS-01 treatment nearly restored their impaired executive function, demonstrating that MMFS-01 may be clinically significant. Due to the strong placebo effects on sleep and anxiety, the effects of MMFS-01 on sleep and anxiety could not be determined. Conclusions: The current study demonstrates the potential of MMFS-01 for treating cognitive impairment in elderly.
    Preview · Article · Oct 2015 · Journal of Alzheimer's disease: JAD
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    • "Cortical atrophy associated with depression was observed in wide regions of the prefrontal cortex and temporal cortex [42] and decreased gray matter volume in the left inferior temporal gyrus was confirmed in an independent study [43]. Depressed AD patients also exhibited greater white matter atrophy in frontal, temporal, and parietal lobes than AD patients without depressive symptoms [44]. One study also reported lesions in the caudate nucleus and lentiform nucleus of AD patients with late-onset depression [45]. "
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    ABSTRACT: Neuropsychiatric symptoms (NPS) such as depression, apathy, aggression, and psychosis are now recognized as core features of Alzheimer's disease (AD), and there is a general consensus that greater symptom severity is predictive of faster cognitive decline, loss of independence, and even shorter survival. Whether these symptoms result from the same pathogenic processes responsible for cognitive decline or have unique etiologies independent of AD-associated neurodegeneration is unclear. Many structural and metabolic features of the AD brain are associated with individual neuropsychiatric symptoms or symptom clusters. In addition, many genes have been identified and confirmed that are associated with symptom risk in a few cases. However, there are no single genes strongly predictive of individual neuropsychiatric syndromes, while functional and structural brain changes unique to specific symptoms may reflect variability in progression of the same pathological processes. Unfortunately, treatment success for these psychiatric symptoms may be lower when comorbid with AD, underscoring the importance of future research on their pathobiology and treatment. This review summarizes some of the most salient aspects of NPS pathogenesis.
    Full-text · Article · Jul 2014 · BioMed Research International
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    • "So, assuming that MCI may be the earliest identifiable clinical stage of dementia, depressive symptoms may be an early manifestation rather than a risk factor for dementia and AD [57]. Recent studies provided also neuroanatomical [58] [59] and neurochemical [60] evidence to support this hypothesis. Furthermore, we also found that severity of agitation in MCI, especially verbally agitated behavior, was predictive for progression to AD. Neuroanatomical studies about agitation in MCI and AD point toward involvement of frontal and temporal brain areas [61]. "
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    ABSTRACT: Background: Behavioral and psychological signs and symptoms of dementia (BPSD) belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). Objective: This study would like to contribute to the understanding of the prognostic role of BPSD in MCI for the progression to dementia due to Alzheimer's disease (AD). Methods: Data were generated through an ongoing prospective longitudinal study on BPSD. Assessment was performed by means of the Middelheim Frontality Score, Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale 30-questions (GDS-30). Cox proportional hazard models were used to test the hypothesis that certain BPSD in MCI are predictors of developing AD. Results: The study population consisted of 183 MCI patients at baseline. At follow-up, 74 patients were stable and 109 patients progressed to AD. The presence of significant depressive symptoms in MCI as measured by the CSDD (HR: 2.06; 95% CI: 1.23-3.44; p = 0.011) and the GDS-30 (HR: 1.77; 95% CI: 1.10-2.85; p = 0.025) were associated with progression to AD. The severity of depressive symptoms as measured by the GDS-30 was a predictor for progression too (HR: 1.06; 95% CI: 1.01-1.11; p = 0.020). Furthermore, the severity of agitated behavior, especially verbal agitation and the presence of purposeless activity, was also associated with progression, whereas diurnal rhythm disturbances were associated with no progression to AD. Conclusion: Depressive symptoms in MCI appear to be predictors for progression to AD.
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