Depression vs. Dementia: How Do We Assess? - Alzheimer ...

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Originally published in The Canadian Review of Alzheimer’s Disease and Other Dementias, September 2009, pages 17-21.
Copyright STA Communications.

Depression vs. Dementia:
How Do We Assess?
Depressive disorder and dementia are common in older people, and may occur separately or
together. Diagnosis is often challenging because of the frequency of symptoms which are
common to both disorders. Unfortunately, underdiagnosis of depression results in missed
opportunities to improve functioning, decreased quality of life and possibly even increased
mortality. Yet, overdiagnosis of depression may result in unnecessary adverse effects of
psychotropic medications. This article suggests approaches to differential diagnosis.

By Lilian Thorpe MD, PhD, FRCP

D     ementia increases with age, with
      an overall prevalence in Canada
of 8% in those 65 years and older,
                                         These include dysthymic disorder,
                                         depressive episodes of a bipolar dis-
                                                                                     least two contradictory directions of
                                                                                     potentially causal influence. One
                                         order, mood disorders secondary to a        hypothesis suggests that depression
2.4% in those aged 65 to 74 years,       medical disorder (such as hypothy-          leads to dementia, and another that
11.1% in those aged 75 to 84 years,      roidism), mood disorders secondary          suggests that dementia itself leads
and 34.5% in those aged 85 years and     to a substance, adjustment disorders        to depression.
older.1 Alzheimer’s disease (AD) is      and bereavement. Depressive disor-              The depression-to-dementia direc-
thought to be the most common type       der is commonly seen in all stages of       tion is supported by evidence that
of dementia in all age groups. How-      adult life and, while its prevalence is     depressive disorder is a risk factor for
ever, younger age groups are more        slightly lower in the elderly,4 its         developing dementia in later life6 and,
likely than older age groups to be       sequelae are probably greater in more       consistent with this, the best-studied
diagnosed with other dementias, such     frail people, exerting a more deleteri-     people with a biological predisposition
as frontotemporal dementia and vas-      ous effect on functional abilities and      to develop AD (those with Down
cular dementia.2                         even increasing the length of stay for      Syndrome) are thought to have a high
   Major depressive disorder is also     hospitalizations related to primary         risk of suffering from depression.7 The
common, but is only one of a number      medical conditions.5 Depressive dis-        association between depression and
of disorders listed in the Diagnostic    order in seniors can occur as part of a     later development of dementia is still
and Statistical Manual of Mental         lifelong recurrent disorder, or it can      not completely understood. One possi-
Disorders (DSM-IV)3 with prominent       present for the first time in old age. It   bility is that depression is an early, pro-
depressive symptoms (Table 1).3          is frequently concurrent with other         dromal phase of dementia,8 and is
                                         medical and mental disorders, includ-       caused by the same pathophysiologic
                                         ing various dementias.                      initiators that result in dementia. There
Lilian Thorpe MD, PhD, FRCP                                                          is also evidence that depression is
Clinical Professor of Psychiatry,
and Professor of Community
                                         Relationships Between                       associated with damage to brain loca-
Health and Epidemiology,                 Dementia and Depression                     tions integral to cognitive processes,
University of Saskatchewan               Dementia and depression have a              such as the hippocampus, possibly
Saskatoon, Saskatchewan                  complicated relationship, with at           by decreasing neurogenesis.9 This

                                                           The Canadian Review of Alzheimer’s Disease and Other Dementias • 17
Vascular Dementia

                                                                                        those with dementia,17,18 although a
  Table 1
                                                                                        recent Danish study suggests that this
  DSM-IV Mental Disorders with Prominent Depressive                                     may now have changed, at least in
  Symptoms3
                                                                                        Denmark.19 Underdiagnosis of dep-
  • Major depressive disorder                                                           ression in demented seniors is clearly
  • Dysthymic disorder                                                                  undesirable, as depressive disorders
  • Bipolar disorder (depressive episode)                                               in the demented elderly have been
  • Mood disorders secondary to a general medical condition                             associated with additional burden, as
  • Mood disorders secondary to a substance (such as a medication)                      described above. Undertreatment
  • Adjustment disorder with depressed mood
                                                                                        with antidepressants may also result
                                                                                        in over treatment of depression-asso-
  • Bereavement
                                                                                        ciated behaviors with benzodi-
                                                                                        azepines and possibly neuroleptics.
process may lower the threshold for          depression in dementia by using four       Adverse effects of benzodiazepines
later observable cognitive loss, even-       different scales in the same popula-       and neuroleptics are well recognized
tually increasing age-adjusted demen-        tion, and found that between 27.5%         and include increased falls, decreased
tia rates. Behaviors associated with         and 53.4% of people with mild AD           alertness, extrapyramidal side effects,
depression, such as heavy alcohol            and between 36.3% and 68.4% with           decreased mobility, decreased func-
uses and vascular risk factors like          moderate to severe AD were found to        tioning and increased mortality.
cigarette smoking,10 may also inde-          rate positive for depression. Studies      Efforts have been made to increase
pendently increase later cognitive           comparing differences in the preva-        the recognition of depression in those
loss, while medications prescribed to        lence of carefully diagnosed depres-       with dementia, and widely used
treat depression, especially those           sive disorders between matched             instruments such as the Minimum
with strong anticholinergic effects,         demented and non-demented popula-          Data Set20 include quality indicators
could conceivably have adverse cog-          tions are not frequent, but suggest that   to alert administrators of patients with
nitive effects, although this effect is      motivational deficits in dementia may      likely depression who are not being
likely more transient.                       be the greatest difference between         treated with antidepressants. Review
    The dementia-to-depression dir-          these groups, rather than typical          of these quality indicators may pre-
ection in the potentially causal rela-       DSM-IV major depressive disorder.13        cipitate discussion with attending
tionship between the two disorders is        However, regardless of the exact           physicians, who have the opportunity
supported by findings that people            prevalence of formally diagnosed           to institute appropriate treatment.
with dementia appear to have a high-         depressive disorder in dementia, it            Unfortunately, this process may
er prevalence of depression.11               does seem that depressive syndromes        also result in an overdiagnosis of
However, prevalence rates vary wide-         are very common in those with              depressive disorder due to the high
ly depending on the study population         dementia, and that this comorbidity        prevalence of behavioral symptoms
(psychiatric outpatients, Alzheimer          causes increased deficits in function-     in dementia such as apathy and reac-
registries, old-age homes), instru-          ing, increased problematic behav-          tive mood symptoms, which overlap
ments used, and diagnostic defini-           ior,11 increased nursing-home place-       with those seen in major depressive
tions. Most problematically, the term        ment,14 increased caregiver stress,15      disorder. Treatment with antidepres-
depression is used to denote different       and increased mortality.16                 sants is increasingly also known to be
clinical concepts, which are not                                                        associated with adverse effects, most
always equivalent to a diagnosis of          Under- and Overdiagnosis of                problematically in older, frail popula-
DSM-IV major depressive disorder.            Depression in Dementia                     tions. Anticholinergic effects of the
    Muller-Thomsen et al12 illustrated       Depressive disorder has long been          tricyclic antidepressants may cause
large variability in the diagnosis of        thought to be underdiagnosed in            confusion, constipation, urinary reten-

18 • The Canadian Review of Alzheimer’s Disease and Other Dementias
Depression vs. Dementia

tion, and visual-accommodation prob-
                                             Table 2
lems. Postural hypotension may cause
falls, and cardiac effects are particu-      DSM-IV Symptoms of a Major Depressive Episode
larly dangerous in overdose. Newer           • Depressed mood
medications, such as selective sero-         • Markedly diminished interest or pleasure
tonin reuptake inhibitors (SSRIs) and        • Significant weight change
venlafaxine, were initially felt to be
                                             • Changes in sleep patterns
much safer, but have been increasing-
                                             • Psychomotor agitation or retardation
ly associated with different, rather
                                             • Fatigue or loss of energy
than fewer, adverse effects.
                                             • Feelings of worthlessness, excessive or inappropriate guilt
    Gastrointestinal side effects and
                                             • Diminished ability to think or concentrate
sleep disturbances appear to be more
                                             • Recurrent thoughts of death, suicidal ideation or suicidal actions
common with this group of medica-
tions. Recent research has suggested
that SSRIs are no less likely than tri-    ing behavior, decreased initiative          le,26 the Geriatric Depression Scale,27
cyclic antidepressants to cause falls.21   and interest (apathy), psychomotor          the Hamilton Depression Rating
They are also associated with a higher     agitation, and poor concentration (in       Scale,28 the Montgomery and Asberg
prevalence of hyponatremia,22 and          advanced dementia) are common in            Depression Rating Scale29 and the
most recently research has suggested       dementia without depression. Reac-          Zung scale.30 Although these scales
they increase fragility fractures.23       tive symptoms such as anxiety and           vary considerably in how much they
Finally, SSRIs have been associated        tearfulness are also seen frequently        are affected by impairments in lan-
with increased apathy,24 even in those     in dementia without depression, and         guage, awareness and comprehen-
who have been appropriately diag-          may be related to retained aware-           sion, none is useful in the later stages
nosed with depression and have             ness of deficits in the early stages of     of dementia. Of greater usefulness in
responded to this medication.              dementia, poor coping skills and            patients with advanced dementia are
                                           disorientation in the later stages, or      the Dementia Mood Assessment
Challenges in the Diagnosis                to the mood lability accompanying           Scale31 and the Cornell Scale for
of Depression in Dementia                  vascular brain disease (which com-          Depression in Dementia.32
Diagnosing depressive disorder in          monly overlaps with AD).                        However, the gold-standard differ-
the context of dementia is often dif-          Much less common in dementia            ential diagnosis of depression in
ficult due to overlapping symptoms         without depression are consistent           dementia is a careful clinical assess-
between depression and dementia,           sadness, marked morning mood                ment, which includes obtaining infor-
communication problems and lack of         worsening, feelings of worthlessness        mation directly from the patient and
insight. Behavioral and psychologi-        or excessive or inappropriate guilt,        from collateral sources, ideally those
cal symptoms of dementia (BPSD)            recurrent thoughts of death, suicidal       with good knowledge of the person.
are integral parts of the clinical pres-   ideation or suicidal actions.               This assessment should include:
entation of dementia, although this                                                     • Careful symptom history
is often thought of as a disorder of       Approach to Clinical                            including:
progressive cognitive decline.             Diagnosis                                       - detailed description;
BPSD includes many of those                A variety of instruments have been              - time course and progression
symptoms also seen characteristi-          developed to screen for depression in              of symptoms; as well as
cally in DSM-IV depressive disor-          the cognitively intact population.              - association with other
ders. Of the core symptoms of              These include the Beck Depression                  confounding factors such as
depressive disorder, listed in Table 2,    Inventory,25 the Centre for Epide-                 environmental stressors which
sleep disturbances, changes in eat-        miological Studies-Depression Sca-                 include:

                                                             The Canadian Review of Alzheimer’s Disease and Other Dementias • 19
Vascular Dementia

 Table 3

 Typical Presentations of Mood Symptoms in Dementia and Depression
 Symptom                     Dementia                                                     Depression
 General response to         Frequent lack of concern or denial about symptoms.           Amplification of and excessive
 cognitive and functional                                                                 preoccupation with deficits.
 decline

 Mood                        Normal most of the time. Unhappiness is reactive             Subacute (weeks) onset of pervasively
                             to circumstances and fluctuates. Labile, especially          sad mood, most of the day and nearly
                             with vascular dementia. Mood often brightens                 every day. Doesn’t brighten much with
                             with stimulation and support.                                stimulation.

 Interest, initiative        Gradual loss of interest and initiative (apathy) over a      Subacute loss of interest and pleasure
                             longer period of time (years rather than weeks). Not         over a few weeks, frequently
                             accompanied by statements of sadness, tearfulness,           accompanied by sad mood and affect,
                             or other distress. Still enjoys activities in a structured   and occasionally statements of guilt,
                             environment.                                                 hopelessness and self-harm.

 Eating behavior and         Gradual loss of weight (over months to years) which Subacute changes (weeks) in appetite
 weight                      is common in dementia. Large increases in weight     leading to increase or decrease
                             may be secondary to decreased activity, medications, in weight.
                             and hyperorality in patients with frontal behavioral
                             presentations (more common in frontotemporal
                             dementia like Pick’s Disease).

 Sleep                       Gradual disruption of the sleep-wake cycle (over             Subacute changes in sleep over a few
                             months to years) due to brain changes of dementia,           weeks (increase or decrease).
                             resulting in frequent night-time wakening and
                             daytime sleeping.

 Psychomotor agitation       Gradual (months to years) increase in agitation,             Subacute (weeks) onset, often worse
                             generally worse during the latter part of the day            in the morning, may be present
                             (sundowning). Patient much worse in unfamiliar               persistently throughout the day.
                             settings (catastrophic reaction), and often seeking          Generally accompanied by other
                             people or places from earlier life experiences.              depressive symptoms such as nihilistic
                                                                                          statements or excessive guilt.

 Psychomotor retardation Seen infrequently in mild to moderate dementia,                  Subacute onset of psychomotor
                         but occasionally in very advanced dementia, and                  retardation (over weeks) in severe
                         may be mimicked by Parkinson’s dementia (facial                  depression.
                         masking, slow motor functioning) or advanced
                         Pick’s Disease.

 Energy                      Generally a normal energy level, but reduced                 Subacute decrease in energy and
                             activity due to poor initiation related to decreased         increased complaints of fatigue.
                             executive functioning.

 Guilt or worthlessness      Uncommon, although transient statements of                   Common in severe depression, usually
                             worthlessness might be seen in times of stress in            accompanied with low mood as well
                             those with preserved awareness of their own decline.         as changes in appetite and sleep.

 Concentration and           Concentration is normal in early dementia, but               Subacute loss of concentration and
 thinking                    impaired in late dementia. Thinking ability declines         sustained focus. Often indecisive and
                             throughout the course of dementia.                           concerned about making mistakes.

 Suicidal thoughts           Uncommon.                                                    Common.
 and actions

20 • The Canadian Review of Alzheimer’s Disease and Other Dementias
Depression vs. Dementia

          - pain;                               consistently low mood and affect              thy without associated sadness, cry-
          - poor nutritional status;            that does not respond to                      ing, or changes in sleep or appetite
          - other medical                       stimulation; hopelessness,                    are unlikely to represent a depressive
            conditions; and                     expressions of guilt; feelings of             disorder, whereas consistently sad
          - recent changes in                   worthlessness; and thoughts of                mood or affect, not brightening dur-
            medications.                        self-harm.                                    ing interpersonal contact and associ-
•   Particular attention should be           • Laboratory investigations, such                ated with subacute changes in sleep
    paid to depressive symptoms                 as hematology, thyroid function,              and appetite are much more likely to
    which are less common in                    electrolytes, vitamin B12, and                represent depressive disorder that
    dementia alone such as:                     drug levels of medications,                   requires medical treatment. Table 3
    - hopelessness;                             known to have a propensity to                 summarizes mood symptoms seen in
    - expressions of guilt;                     cause mood symptoms.                          depression and dementia, with a brief
    - feelings of worthlessness; and            In addition to the above, neuro-              discussion about their more typical
    - thoughts of self-harm.                 imaging might be performed to                    presentation in each disorder.
•   Frontal symptoms, such as                explore the potential contribution of
    disinhibition, perseveration and         vascular pathology to mood lability              Conclusion and Treatment
    decreased initiative, suggest            and apathy, and to rule out other neu-           Issues
    dementias with a strong frontal          rologic problems such as normal-                 Sometimes it is very difficult to make
    component rather than depression.        pressure hydrocephalus.                          a firm diagnosis of depression in the
•   Information about family                    After this assessment, the clini-             context of dementia, especially when
    history of mood disorders,               cian has to weigh the information                the dementia is very advanced. The
    previous personal history of             obtained, taking into account the                clinician will occasionally choose to
    depression and previous response         likelihood that the accumulated                  instigate treatment regardless of
    to therapy for depression.               information represents depression                diagnostic certainty, weighing the
•   Direct interview of the person,          rather than dementia alone. For                  possible benefits versus potential
    paying particular attention to:          example, isolated symptoms of apa-               adverse outcomes of treatment.

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                                                                 The Canadian Review of Alzheimer’s Disease and Other Dementias • 21
Vascular Dementia

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21.1 • The Canadian Review of Alzheimer’s Disease and Other Dementias
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