How Late-Life Depression Affects Cognition: Neural Mechanisms

Late-life depression is a major health problem and a significant cause of dysfunction that warrants closer evaluation and study. In contrast to younger depressed patients, most depressed older adults suffer more severe variants of the disorder, including significant cognitive impairments. These cognitive changes add to the severity of symptoms and disability that older depressed patients face and likely reflect compromise of certain neural circuits, linking cognitive impairment to late-life depression. Studies examining clinical correlates, neuropsychological testing, and functional and anatomic imaging have yielded a clearer understanding of the neural mechanisms underlying cognitive deficits in late-life depression. This article discusses cognitive impairment in geriatric depression and how developing a better understanding of its neural correlates may lead to improved understanding and outcome of this specific disorder.     

The clock drawing test as a measure of executive dysfunction in elderly depressed patients

The aims of this research were to determine whether performance on the Clock Drawing Test (CDT) could accurately distinguish between older patients with depression and older patients with depression and previously undocumented executive dysfunction and to determine if there was a correlation between CDT and depression severity. The authors studied 52 patients consecutively admitted to a geriatric psychiatry inpatient unit of a university hospital who met DSM-IV criteria for major depression or depression not otherwise specified but had no concurrent diagnosis of dementia. All the subjects completed the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (DRS), and the CDT, as well as the Geriatric Depression Scale (GDS). The patients were divided into 2 subgroups based on the DRS score: <129 (cognitive impairment) versus = 129. Results indicated that the depressed patients with a score of DRS <129 had significantly lower CDT scores than did patients with DRS = 129 and normal comparison subjects (P< .01). The results support the hypothesis that CDT score is lower in elderly depressed patients with executive dysfunction versus nondepressed seniors as well as depressed patients without executive dysfunction.     

Executive dysfunction in geriatric depression

OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD: The attention and executive functioning of 40 adults with major depression were compared with those of 40 healthy comparison subjects; 20 subjects were 20-60 years old, and 20 were > or =61 years. It was hypothesized that depressed subjects, regardless of age, would perform more poorly than comparison subjects on both attention and executive tasks but that the older depressed adults would evidence significantly greater impairment on executive measures. RESULTS: A significant interaction between age and depressive status was noted for tasks of executive functioning, while no age-depression interaction was found for tasks of selective or sustained attention. Older depressed adults demonstrated the slowest psychomotor speed and the poorest performance on tasks requiring set shifting, problem solving, and initiation of novel responses. CONCLUSIONS: Patients with late-life depression have significant impairment in executive functioning. These findings can guide the development of stimulated functional neuroimaging paradigms that may clarify the pathophysiology of geriatric depression. Timely identification of attentional and executive processes fundamental to the daily functioning of depressed older adults may lead to compensatory strategies that will improve the outcomes of late-life depression.     

IADL functions, cognitive deficits, and severity of depression: a preliminary study.

OBJECTIVE: Despite the documented association of cognitive dysfunction with impairment in instrumental activities of daily living (IADLs) in geriatric depression, the relationship among deficits in distinct IADLs with severity of depression and specific cognitive impairments remains to be clarified. The authors examined the relationship of depression severity and the cognitive domains of attention, initiation/perseveration, construction, conceptualization, and memory to nine distinct IADLs. METHODS: The subjects were 105 nondemented elderly patients but with impairment in at least one IADL and a history or presence of major depression. Impairment in IADLs and severity of depression were assessed with the Philadelphia Multilevel Assessment Instrument (MAI) and the 24-item Hamilton Depression Rating Scale (Ham-D), respectively. Cognitive dysfunction was assessed with the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale (DRS). RESULTS: Six IADLs were influenced by impairment in at least one of the cognitive domains. Abnormal scores in initiation/perseveration, an aspect of executive dysfunction, was the cognitive impairment affecting most IADLs; it interfered with the ability to shop for groceries, prepare meals, take medicine, and manage money. Impairment in initiation/perseveration had a most prominent effect in the presence of depressive symptoms and affected shopping for groceries and preparing meals. Lack of interest and motivation, part of the depressive syndrome, compounded by behavioral abnormalities resulting from executive dysfunction, may account for this interaction. CONCLUSIONS: These relationships may provide the background for developing interventions targeting functional deficits associated with specific cognitive dysfunctions and depression.     

Depression and cognition in older adults

PURPOSE OF REVIEW: Recognition that depression is associated with neurocognitive impairment and renewed recent interest in milder forms of cognitive impairment in older people (typified by the concept of mild cognitive impairment) have stimulated researchers to investigate the relationship between depression and cognitive impairment. This review identifies and clarifies recent progress in this rapidly developing research area. RECENT FINDINGS: Neurocognitive impairment persists in most depressed older people after clinical recovery, and slowed information processing speed and possibly executive dysfunction and vascular risk factors underlie this. Most studies suggest that this neurocognitive impairment in turn leads to increased mild cognitive impairment as well as dementia. White matter disease appears to directly contribute to depression in older people and this worsens over time. Polymorphisms in the serotonin transporter gene may be a key risk factor as well, and depression worsens vascular outcome in peripheral arterial disease. SUMMARY: Clinicians should be aware that neurocognitive deficits persist and have an adverse effect on outcome, and that vascular risk factors may contribute to these deficits.     

The association between depressive and cognitive symptoms in amnestic mild cognitive impairment

BACKGROUND: Depressive symptoms are frequently observed in older adults with mild cognitive impairment (MCI). However, little is known regarding the cognitive characteristics of this important subgroup. METHODS: We examined executive functions (controlled inhibition) and verbal episodic memory in 33 healthy older adults (control group), 18 older adults with amnestic MCI plus subclinical depressive symptoms (a-MCI/D+ group), and 26 older adults with amnestic MCI but no depressive symptoms (a-MCI group). RESULTS: Compared to the a-MCI and control groups, patients with a-MCI/D+ showed poor controlled inhibition. Moreover, in verbal episodic memory these patients recalled fewer words than control participants on immediate free, delayed free, and delayed total (free plus cued) recall. Performance on immediate recall suggested a self-retrieval deficit, but delayed performance also revealed the existence of an encoding impairment. In the a-MCI group, participants exhibited normal performance on the executive task, but pervasive memory impairment; the memory deficit concerned free and total recall on both immediate and delayed tasks, suggesting the existence of encoding and self-retrieval disturbances. CONCLUSIONS: This study reveals differences between the pattern of cognitive impairment for a-MCI/D+ and a-MCI subgroups particularly at the level of executive capacities. In terms of memory functioning, the differences between the subgroups were more subtle; more studies are needed in order to better characterize the memory impairment of a-MCI/D+ and a-MCI patients.     

Dimensions of Poststroke Depression and Neuropsychological Deficits in Older Adults

ObjectivePoststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults with PSD and to evaluate their relationship to cognitive functioning.DesignCross-sectional factor and correlational analyses of patients with poststroke depression.SettingPatients were recruited from the community and from acute inpatient stroke rehabilitation hospitals.ParticipantsParticipants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Åsberg Depression Scale; MADRS).InterventionNone.MeasurementsMADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language.ResultsThere were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment.ConclusionPSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment.     

The Independent Contributions of Cognitive Impairment and Neuropsychiatric Symptoms to Everyday Function in Older Adults

The everyday functional capacities of older adults are determined by multiple factors. The primary goal of the present study was to evaluate whether apathy and depression have unique influences on degree of functional impairment, independent of the effects of specific cognitive impairments. Participants included 344 older adults (199 normal, 87 with MCI, 58 with dementia). The Everyday Cognition (ECog) scales were used to measure both global and domain-specific functional abilities. Neuropsychiatric symptoms of depression and apathy were measured by the Neuropsychiatric Inventory (NPI), and specific neuropsychological domains measured included episodic memory and executive functioning. Results indicated that worse memory and executive function, as well as greater depression and apathy, were all independent and additive determinants of poorer functional abilities. Apathy had a slightly more restricted effect than the other variables across the specific functional domains assessed. Secondary analysis suggested that neuropsychiatric symptoms may be more strongly associated with everyday function within cognitively normal and MCI groups, while cognitive impairment is more strongly associated with everyday function in dementia. Thus, a somewhat different set of factors may be associated with functional status across various clinical groups.     

Does impaired executive functioning differentially impact verbal memory measures in older adults with suspected dementia?

The purpose of this study was to examine whether executive dysfunction differentially impacts list-learning and story recall tasks in a sample of older adults referred for suspected cognitive impairment. Older adults (N = 61) with mild cognitive impairment (MCI) or probable mild dementia, and those who did not meet criteria for diagnosis of dementia, were assessed using measures of executive function and verbal memory. Two groups were established based on performance on measures of executive function: (a) the No Executive Dysfunction group (NoED; n = 33) consisted of persons without impairment on any obtained measures of executive function; and (b) the Executive Dysfunction group (ED; n = 28) contained persons with impairment on at least one of the measures of executive function. The two groups were compared on performance on two measures of verbal memory, the California Verbal Learning Test-II (CVLT-II) and the Logical Memory (LM) subtest from the Wechsler Memory Scale-Revised (WMS-R). The NoED group performed significantly better than the ED group on the total learning and short delay free recall trials of the CVLT-II. However, there were no significant differences between the groups on the other indices of the CVLT-II (i.e., long delay free recall, recognition, recall repetitions, recall intrusions, or recognition false-positives) or on the immediate and delayed recall trials of the LM measure. These results support previous research demonstrating the impact of executive dysfunction on the acquisition of and short-delay retrieval of verbal information in older adults with suspected cognitive impairment.     

Post-stroke depression, executive dysfunction and functional outcome

The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was subjected to a comprehensive neuropsychological examination 3-4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42-1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke.     

Engagement in Socially and Interpersonally Rewarding Activities as a Predictor of Outcome in “Engage” Behavioral Activation Therapy for Late-Life Depression

ObjectiveLoneliness and social isolation are associated with depressive symptoms, cognitive and physical disabilities, and increased risk of mortality among older adults. Socially rewarding activities reduce loneliness, and neurobiological evidence suggests that these activities may activate neural reward systems in older adults to a greater extent than other rewarding experiences. The current study was designed to investigate whether engagement in social and interpersonal activities (i.e., exposure to social rewards) predicts subsequent increase in behavioral activation and reduction in depressive symptoms in reward exposure treatment for late-life depression.MethodsForty-eight older adults without cognitive impairment and with major depression received nine sessions of “Engage” psychotherapy. Behavioral activation and depression severity were assessed by trained raters at baseline and weeks 6 and 9. Patients’ weekly behavioral plans were categorized into three groups: 1) solitary activities; 2) social-group activities (attending a social gathering or a social setting such as church or a senior center); and 3) interpersonal-individual activities (engaging in an interpersonal interaction with a specific friend or family member).ResultsMixed-effects models showed reduction in depression severity and increase in behavioral activation over time. In linear regression models, a higher percentage of interpersonal-individual activities (but not solitary or social-group activities) predicted subsequent increase in behavioral activation and improvement of depression.ConclusionThese findings highlight the importance of understanding the effects of engagement in specific types of rewarding activities in behavioral activation treatments for late-life depression. Exposure to socially rewarding interpersonal interactions could contribute to the efficacy of psychotherapy for late-life depression.     

Separating mood disturbance from mild cognitive impairment in geriatric depression

Disentangling depression from dementia remains one of the most difficult clinical challenges for psychiatrists caring for older adults. The relationship between geriatric depression and dementia is complex for several reasons. First, cognitive impairment is often a prominent feature of depression in the elderly. Cognition may improve with successful treatment of depression but it may not normalize. Indeed, marked memory impairment in older depressed individuals may indicate a prodromal state of dementia. This review will examine issues related to depression and cognitive disorder in the elderly. The author will provide an evidence-based approach to separate mood disorder from cognitive disorder among older adults.     

Separating mood disturbance from mild cognitive impairment in geriatric depression

Disentangling depression from dementia remains one of the most difficult clinical challenges for psychiatrists caring for older adults. The relationship between geriatric depression and dementia is complex for several reasons. First, cognitive impairment is often a prominent feature of depression in the elderly. Cognition may improve with successful treatment of depression but it may not normalize. Indeed, marked memory impairment in older depressed individuals may indicate a prodromal state of dementia. This review will examine issues related to depression and cognitive disorder in the elderly. The author will provide an evidence-based approach to separate mood disorder from cognitive disorder among older adults.     

Problem solving therapy for the depression-executive dysfunction syndrome of late life

BACKGROUND: The 'depression executive dysfunction syndrome' afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non-pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression. METHODS: This paper focuses on problem solving therapy (PST) because it targets concrete problems that can be understood by patients with executive dysfunction and trains patients to address them using an easy to comprehend structured approach. RESULTS: We suggest that PST is a suitable treatment for patients with the depression-executive dysfunction syndrome because it has been found effective in uncomplicated geriatric major depression and in other psychiatric disorders accompanied by severe executive dysfunction. Furthermore, PST can address specific clinical features of depressed patients with executive dysfunction, especially when modified to address difficulties with affect regulation, initiation and perseveration. CONCLUSIONS: A preliminary study suggests that appropriately modified PST improves problem solving skills, depression and disability in elderly patients with the depression-executive dysfunction syndrome of late life. If these findings are confirmed, PST may become a therapeutic option for a large group of depressed elderly patients likely to be drug resistant.     

Executive dysfunction and disability in elderly patients with major depression.

The authors studied 126 elderly patients without dementia and with unipolar major depression. Impairment in instrumental activities of daily living (IADLs) was significantly associated with age (P<0.0001), gender (P<0.001), medical burden (P=0.013), severity of depression (P=0.01), initiation/perseveration (IP; P=0.035), and IP x depression (P=0.029). Depression was associated with IADL impairment mainly in patients with impaired IP. Among the cognitive impairments, IP-only contributed significantly to IADL impairment, whereas attention, construction, conceptualization, and memory did not. Attention to executive function and disability may guide clinical management and lead to development of innovative pharmacological and behavioral interventions.     

Apathy and cognitive performance in older adults with depression

OBJECTIVES: Recent studies have linked apathy to frontal lobe dysfunction in persons with dementia, but few studies have explored this relationship in older, depressed persons without dementia. We examined the association between apathy and cognitive function in a group of older persons with major depression using standardized neuropsychological tests. We hypothesized that presence of apathy in depression is associated with poorer frontal executive performance. METHODS: We analyzed data from 89 older adults with major depression. We defined apathy using four items from the Hamilton Psychiatric Rating Scale for Depression which reflect the clinical state of apathy, including 'diminished work/interest,' 'psychomotor retardation,' 'anergy' and 'lack of insight.' RESULTS: Apathy most strongly correlated with two verbal executive measures (Stroop C and FAS), a nonverbal executive measure (Wisconsin Card Sorting Test-Other Responses), and a measure of information processing speed (Stroop B). Apathy was not associated with age, sex, education, medical illness burden, Mini-Mental State Examination score and Full Scale IQ score. Stepwise regression analyses of significant cognitive tests showed that apathy alone or apathy plus depression severity, age, or education accounted for a significant amount of the variance. CONCLUSIONS: The results of this study provide support for an apathy syndrome associated with poorer executive function in older adults with major depression.     

Executive dysfunction and apathy predict functional impairment in Alzheimer disease.

OBJECTIVE: The purpose of this study was to examine the extent to which executive cognitive dysfunction and frontally-mediated behavioral disturbances are associated with functional impairment in patients with mild-to-moderate Alzheimer disease (AD). METHODS: Patients with AD (N=45) completed the Mattis Dementia Rating Scale, and patients' caregivers completed the Frontal Systems Behavioral Inventory and a modified form of the Lawton and Brody Activities of Daily Living (ADLs) Questionnaire. RESULTS: Multiple-regression analyses revealed that executive cognitive dysfunction and apathy scores accounted for 44% of the variance in instrumental activities of daily living; executive cognitive dysfunction alone explained 17% of the variance in instrumental ADLs, and apathy scores explained an additional 27%. Executive dysfunction and frontal-behavioral impairment explained 28% of the variance in basic ADLs (BADLs), and, after accounting for executive dysfunction, apathy was the only symptom found to explain additional unique variance in BADLs. CONCLUSION: These findings suggest that specific cognitive and behavioral symptoms are associated with functional impairment in patients with AD.     

An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.     

Sleep-Disordered Breathing and Cognition in Older Adults

Both sleep-disordered breathing (SDB) and cognitive impairment are common among older adults, yet few studies have examined their relationship within this population to determine whether the effect of SDB on cognition is of a magnitude similar to or greater than that observed in younger and middle-aged adults. Here, we review the extant literature and report that studies are largely supportive of an association between SDB and cognitive impairment in older adults, particularly in the domains of attention/vigilance, executive function, and verbal delayed recall memory. Presence of the APOE4 allele may confer increased vulnerability to SDB-associated cognitive dysfunction among elderly individuals. Although findings are mixed, there is strong evidence to suggest that SDB-related intermittent hypoxemia is the primary mechanism through which SDB exerts its adverse effects on cognition. We propose a microvascular model in which chronic intermittent hypoxemia causes vasculopathy that ultimately is expressed as cognitive impairment in the older adult. However, it remains unclear whether the effects of SDB on cognition are the same regardless of age or whether there is a synergistic interaction between age and SDB.     

Relationship of neuropsychological performance to functional status in nursing home residents and community-dwelling older adults.

OBJECTIVES: The authors examined the association between neuropsychological tests of executive functioning and episodic memory and functional disability in nursing home residents versus community-dwelling older adults. METHODS: The neuropsychological performance of 96 residents from the Jewish Home and Hospital, Bronx, NY and 192 gender- and age-matched older adults from residential communities in the New York metropolitan area was assessed in eight tasks (Word List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency, Trailmaking A and B, and Digit Symbol Substitution). Functional status was derived from the Clinical Dementia Rating scale (CDR) extended activities of daily living scores. Regression analyses were performed to test for differences in cross-sectional age-gradients for cognitive and functional status between nursing home residents and community-dwellers. Furthermore, regression analyses, controlling for age, gender, dementia status, and education, were performed to determine the association between neuropsychological performance and functional status, comparing domains of executive functioning and memory. RESULTS: Community-dwelling older adults showed age-related deficits both in overall cognitive status and functional disability, which were larger in nursing home residents. Executive functioning was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, overall cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning is associated with functional deficits in both community-dwelling older adults and nursing home residents. Measures of executive functioning may prove useful in intervention studies aimed at delaying institutionalization.