Behavior and Personality Disturbances

Depression

The true prevalence of depression in AD is controversial, with estimates up to 86%. One reason for the mixed findings lies in the different methods used to assess depression in AD, such as family interviews and patient self-report. Some symptoms of depression are confounded with components of AD (e.g., concentration, energy, interest). The probability of depression in AD appears to be greater if there is a history of depression either in the patient or in the family. Table 9.4 suggests differences between the signs of depression and confounding signs of dementia. Interestingly, there does not appear to be a clear relationship between depressive symptoms and severity of AD ( ). Depression is associated with greater social and functional impairments in patients with AD ( ), although others have not observed a correlation between depression and functional impairment ( ).

Selective serotonin reuptake inhibitors (SSRIs) remain the preferred mode of treatment for depression in AD, and, although sertraline and citalopram have been shown to be effective ( ), findings are mixed. Although discontinuation of current antidepressant treatment shows worsening ( ), one review ( ) suggests that secondary to the absence of benefit compared with placebo and the increased risk of adverse events ( ), the use of antidepressants for first-line treatment of depression in AD should be reconsidered. One recent paper formulated recommendations for future work:

• 1.

  It remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm.

• 2.

  Further research is required to evaluate the impact that treatments for depression in dementia have on carers in terms of quality of life and the time they spend caregiving.

• 3.

  Alternative biological and psychological therapies for depression in dementia should be considered, including new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g., cholinesterase inhibitors).

• 4.

  Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services.

• 5.

  Further work is needed to investigate the costs of depression in dementia, including caregiver burden and moderators to the treatment effects ( ). A recent publication suggests that antidementia medication and nonpharmacological interventions can be potential choices ( ).

Apathy

Apathy , defined as diminished motivation not attributable to decreased level of consciousness, cognitive impairment, or emotional distress, is among the most common behavioral changes noted in AD. Assessment of apathy in AD may be difficult because it may be unclear whether decreased activity is due to apathy or inability to perform activities. Consistent with expectations based on frontal subcortical circuitry, apathy in AD has been shown to be associated with bilateral reductions in gray matter volume in the anterior cingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and putamen ( ). Apathy in AD is associated with greater functional and cognitive impairment ( ) and lower quality of life ( ).

Aggression

Aggressive verbalizations and acts are common in AD. Reported prevalence rates range from 25% to 67%; studies have indicated that verbal aggression is more common in men and in individuals with delusions or agitation ( ) and is associated with increased placement in skilled nursing facilities. Sertraline has been associated with a 38% response rate for the treatment of aggression and irritability in AD ( ).

Psychosis

Prevalence rates of psychotic symptoms in AD range from 10% to 73%, with rates in clinical populations exceeding community-based samples. Interestingly, hallucinations and delusions are significantly less common among individuals with early-onset AD ( ). Once present, delusions recur or persist for several years in most patients with AD ( Fig. 9.6 ). The presence of hallucinations is associated with increased placement in skilled nursing centers.

The delusions reported in AD are typically paranoid type, nonbizarre, and simple. Complex or bizarre delusions seen in patients with schizophrenia are conspicuously absent in patients with AD. However, misidentification phenomena are common in AD. Hallucinations in AD are more often visual than auditory, whereas the reverse is true for schizophrenia ( Table 9.5 ).

Previously it was believed that individuals with AD experienced delusions secondary to significant cognitive difficulties. Evidence from neuropsychological investigations suggests more executive and frontal dysfunction in AD with psychotic symptoms than AD without these symptoms. The presence of delusions in AD is associated with poorer performance on the Frontal Assessment Battery (FAB) but was not related to global measures of cognitive impairment (i.e., Mini Mental Status Examination [MMSE]) ( ). However, more recent research has identified additional correlates and biological markers of psychosis. For example, delusions have been associated with reduced gray matter volume in the inferior right frontal gyrus and the inferior parietal lobule ( ). Persons with AD and hallucinations (but not delusions) are at significantly increased risk for mortality ( ).

Behavioral Disruption

Atrophy within the frontal lobes leads to disruption of the frontosubcortical circuits and the characteristic behavioral syndromes in FTD. Two classic behavioral syndromes have been described among individuals with FTD: an apathetic and a disinhibited subtype. Apathy is a very common symptom in individuals with FTD. Individuals may show little concern for personal hygiene and may appear unkempt. Moreover, symptoms of orbitofrontal syndrome, such as disinhibition, poor impulse control, tactlessness, and poor judgment are common. Loss of empathy, mental inflexibility, and stereotyped behaviors are also common. Symptoms similar to those observed in Klüver-Bucy syndrome, such as hyperorality and hypersexuality, may occur in late stages. Frequently the family members and caregivers are the ones who report these behavioral disturbances, because many patients with FTD experience reduced insight into their current difficulties. Behavioral change to varying degrees has been described in all FTD syndromes, including PPA ( ), although they frequently are less severe and/or occur later in the progression of the illness.

From a pathological perspective, individuals with FTD vary with regard to the degree to which the frontal versus temporal lobes and right versus left hemispheres are affected. Significant research has looked at the relationship between patterns of behavioral syndromes and underlying neuropathology (see , for a review). Individuals with bvFTD typically exhibit greater frontal versus temporal atrophy, which is typically symmetrical. Evidence shows that individuals with bvFTD and primarily apathetic behavioral changes show greater frontal involvement, particularly from/in the right dorsolateral prefrontal cortex ( ). Individuals with primarily disinhibited behavioral change show greater involvement of the right mediotemporal limbic and temporal lobe ( ), although others have described increased atrophy within the left dorsolateral prefrontal cortex ( ). Individuals with semantic dementia (SD), a variant of PPA, most typically exhibit atrophy and dysfunction within the left anterior temporal lobe, whereas individuals with SD and behavioral changes are more likely to also exhibit changes in the ventromedial and superior frontal lobes. Individuals with progressive nonfluent aphasia (PNFA), another PPA variant, are more likely to show changes in left frontal and perisylvian areas.

No curative treatments exist for FTD. However, there has been some success with pharmacological intervention for behavioral dyscontrol. Although few large-scale studies have been completed, evidence suggests that behavioral disturbances such as disinhibition, overeating, and compulsions may show some response to treatment with SSRIs ( ).

Anosognosia

As noted in the consensus criteria, individuals with FTD frequently exhibit anosognosia. This loss of insight may manifest as an inability to perceive symptoms or a lack of concern for their current difficulties. Among individuals with frontotemporal lobar degeneration (FTLD), individuals with bvFTD exhibit greater anosognosia than individuals with the aphasic subtypes of FTLD ( ). Patients with FTD frequently describe significantly fewer problems with cognition and behavior than what their caregivers describe. Moreover, this observed discrepancy between patient and caregiver report is greater among individuals with FTD than in individuals with AD, particularly for language, behavior, and functioning difficulties ( ). Severity of anosognosia is not typically associated with severity of dementia ( ). The relationship between impaired awareness and specific neuropathology is somewhat unclear. Some studies have shown an association between impaired awareness and right frontal disruptions ( ), whereas others have shown a link between anosognosia and involvement of the right temporoparietal cortex ( ).

Depression

The mean reported prevalence of depression in VaD is 32%, although rates vary widely between studies ( ). Sample source likely influences the reported prevalence rates, with community samples endorsing lower rates of depression than clinic samples. Individuals with VaD and depression are less likely to have had a stroke and are more likely to have a prior history of depression and impairments in memory or attention than patients with VaD without depression. The relationship between age and depression in VaD is unclear, with increased rates of depression being reported in both younger and older samples.

Additional Behavioral and Psychiatric Disorders

Apathy in VaD is associated with increased impairment in both basic and instrumental activities of daily living ( ). This relationship is particularly apparent in patients with VaD who have also experienced a stroke. Rates of psychotic symptoms are similar in AD and VaD. Delusions (33%) and visual hallucinations (13%–25%) are reported in VaD and are associated with impaired cognitive functioning ( ). Care must be taken in the assessment of delusions in VaD and in dementia in general. It is important to differentiate delusions from confabulation or thought processes based on impaired cognitive functioning.

Depression

Depression is the most common psychiatric disturbance in persons with PD. Depending on the threshold for diagnosis and sample assessed, reported rates vary. Depression may predate the onset of motor symptoms in PD ( ). Risk factors for depression in PD include greater cognitive impairment, earlier disease onset, and family history of depression. Depression is not associated with increased motor symptom severity ( ). The correlation between depression and disability is equivocal. Although the precise etiology is unknown, it is believed that depression in PD results from disruptions in dopamine (D2), noradrenaline, and serotonin pathways ( ).

Very few well-controlled studies have assessed antidepressant therapy in PD. Available research suggests that SSRIs are well tolerated and likely effective in the treatment of depression in PD (see , for a review). SSRIs are frequently implemented as a first-line therapy for depression in patients with PD, although SSRIs may worsen motor symptoms. In such cases, tricyclic antidepressants may be an effective alternative. Successful treatment of depressive symptoms with an SSRI may also result in reductions in anxiety and decreased disability.

Psychosis

Hallucinations, typically visual, occur in up to 40% of patients with PD, with 16% reporting delusions ( ). Psychotic symptoms are very uncommon early in the course of PD. Other diagnoses such as dementia with Lewy bodies (DLB) should be considered in patients exhibiting hallucinations early in the course of the disease. Table 9.7 summarizes important distinctions between psychosis in PD and DLB. Psychotic symptoms are more common in PD patients with greater cognitive impairment, longer duration of illness, greater daytime somnolence, and older age and in those who are institutionalized. Psychotic symptoms are strong predictors of nursing home placement and mortality in PD ( ).

Historical accounts of PD rarely described psychotic symptoms, and it has been postulated that psychosis occurred secondary to dopamine agonist use. Although dopamine agonists may contribute to the development of psychosis, additional factors are also important. For example, individuals with psychosis are more likely to exhibit cholinergic deficits and have Lewy bodies in the temporal lobe observed at autopsy ( ).

Intervention for remediation of psychotic symptoms in PD can involve several processes. Discontinuation of anticholinergics, selegiline, and amantadine before reducing l -dopa is recommended. Following these discontinuations, reduction and simplification of dopamine agonists may be beneficial. Atypical antipsychotics are added only when a reduction of other medications has not resulted in improvement, because even atypical antipsychotics have been associated with worsening of PD motor symptoms ( ).

Apathy

Individuals with PD often experience increased rates of apathy. Estimates of apathy in PD have ranged from 16.5% to 40.0%. Individuals with apathy exhibit greater cognitive impairment ( ). Controlled clinical trials for apathy in PD are very limited. Environmental and other behavioral interventions including establishment of a routine, structured schedule, and cuing from others can be helpful in some settings. Dopamine agonists, psychostimulants, modafinil, dopamine agonists, and testosterone have been reported to be helpful in decreasing apathy (see , for more detailed information).