PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs.Brain failure - Alzheimer's dementia, Dementia with Lewy bodies (DLB).

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Brain failure - Alzheimer's dementia, Dementia with Lewy bodies (DLB)

Brain failure - Alzheimer's dementia, Dementia with Lewy bodies (DLB)

Date Created: 09/02/1997   Last Modified: 20/01/2003   Last Checked: 20/01/2003

Brief summary

  1. Alzheimer's dementia, Dementia with Lewy bodies (DLB), Parkinson disease and depression frequently occur together.
  2. Dementia with Lewy bodies (DLB): may be second most common form of dementia (after Alzheimer's); cognitive fluctuations, visual hallucinations, systematized delusions, repeated falls, apathy and severe anxiety. Patients with DBL are extra-sensitive to neuroleptics which may increase mortality. Reactions include neuroleptic malignant syndrome (NMS) like symptoms and cognitive deterioration as well as Parkinsonian side effects
  3. Alzheimer's Dementia. most frequent disorders (%) are:-- aggression (95%), anxiety/agitation (70%), hypophagia (70%), diurnal rhythm disturbance (65%) and "trailing & checking", ie following carer (60%), paranoid ideas (45%)
  4. Behavioural disorders, rather than memory, are the main reason why caregivers place patients with dementia in nursing homes.
  5. Control of problem behaviours may be achieved with various other drugs; as far as possible avoid all drugs which lower levels of any neurotransmitter, especially neuroleptics
  6. Benzodiazepines may induce delirium and caution is advised; it is helpful to avoid long acting ones and those with active metabolites.
  7. Serotonergic drugs tend to reduce certain kinds of aggressive behaviours.
  8. Because of interactions and special pharmacological factors in the elderly this is a challenging area.
  9. Easily precipitated delirium indicates prodromal dementia. Also major surgery may precipitate cognitive decline.

Alzheimer's dementia, Dementia with Lewy bodies (DLB), Parkinson disease and depression frequently occur together. This is probably because they share a common degenerative aetiology.

Special care in the selection of drug treatment is desirable because drugs that may be good for depression may be bad for dementia and Parkinson disease; eg TCAs (anti-muscarinic effects) make memory worse and may cause delirium, SSRIs may lower dopamine and thus exacerbate extra-pyramidal side effects of neuroleptics and Parkinson disease.

Dementia with Lewy bodies (DLB)

This is probably the second most common form of dementia (after Alzheimer's).

Core features

In Dementia with Lewy bodies there is a wide range of psychopathology that is only weakly correlated with severity of cognitive impairment. Some mild extra-pyramidal signs are present in most patients with cognitive fluctuations, visual hallucinations, systematized delusions, repeated falls, apathy and severe anxiety. Patients suffering from Dementia with Lewy bodies are extra-sensitive to the side effects of neuroleptics which may increase mortality. Reactions include neuroleptic malignant syndrome (NMS) like symptoms and cognitive deterioration as well as Parkinsonian side effects.

Psychopathology in Dementia with Lewy bodies vs Alzheimer's (at initial diagnosis / presentation)

Five symptoms seem to be more common in Dementia with Lewy bodies; hallucinations, delusions, anxiety, anhedonia, and loss of energy; but especially delusional misidentification and hallucinations.

There may be two types of episodic cognitive deterioration: one characterized by disturbances of attention and alertness, and another characterized by severe disturbances of orientation in time and place, and misidentification of people.

A fluctuating level of conciousness is characteristic of DLB.

Alzheimer's Dementia. (see other notes for diagnostic criteria)

The most frequent disorders (%) are:-- aggression (95%), anxiety/agitation (70%), hypophagia (70%), diurnal rhythm disturbance (65%) and "trailing & checking", ie following carer (60%), paranoid ideas (45%).

Hallucinations occur in only 25% of cases.

Alzheimer’s symptoms are very variable and may come and go. A significant proportion of patients will be free of a particular symptom after approximately nine months. This observation can be used to guide the duration of treatment trials for particularly problematic symptoms. A recent large sample of autopsy confirmed Alzheimer’s cases showed a prevalence of symptoms (over the whole course of their illness) as follows:--

  • verbal aggression 94%
  • sadness 81%
  • hypophagia 70%
  • anxiety 70%
  • aggressive resistance 69%
  • disturbed diurnal rhythm 65%
  • physical aggression 62%
  • trailing and checking 62%
  • aimless walking 48%
  • being returned home 48%
  • attempts to leave home 46%
  • persecutory ideas 46%
  • walking more 42%
  • hyperphagia 27%
  • hallucinations 25%

There is little relationship between MMSE score and the appearance or disappearance of any particular symptom.There is no robust timing of onset for specific behaviours or symptoms in relation to MMSE score. For most symptoms 25% of patients will be free from them after 9 months.

Behavioural disorders, rather than memory, are the main reason why caregivers place patients with dementia in nursing homes.

The presence of hallucinations may be associated with more rapid cognitive decline in Alzheimer's disease (ie moving along the spectrum towards Dementia with Lewy bodies).

Extrapyramidal signs may be the strongest predictor of severity of depression. Depression tends to be more severe in vascular dementia.

Drug responsive symptoms are usually said to be:-- anxiety, verbal and physical agitation, hallucinations, delusions, uncooperativeness and hostility. In this context 'drug responsive' refers to neuroleptics. My interpretation of the most recent evidence is that it indicates neuroleptics are best used sparingly for short periods, or not at all. That applies to most forms of 'brain failure'

Unresponsive symptoms:-- wandering, hoarding, unsociability, poor self-care, screaming and other stereotyped behaviour seem to be unresponsive to all drugs. However, recent evidence indicates anti-cholinesterase drugs may be helpful.

Risperidone at low dosages (0.5 to 2 mg/day) is touted for the treatment of behavioural symptoms in dementia because of its negligible anti-muscarinic adverse effects. It is doubtful if it is any better than other old (somewhat less expensive) neuroleptics with low anti-muscarinic potency, eg fluphenazine, haloperidol, thiothixene and trifluoperazine. The use of neuroleptics is limited by side effects, particularly anti-muscarinic activity, especially in dementia of the Alzheimer and Lewy body types.

Control of problem behaviours may be achieved with various other drugs; as far as possible avoid all drugs which lower levels of any neurotransmitter, especially neuroleptics and drugs with muscarinic blocking effects. (see notes on donepezil)

Tegretol and Epilim may help agitated, wandering, and aggressive behaviour; Tegretol can give problems with interactions, I find Epilim useful; it is not established or approved for these indications.

Benzodiazepines may induce delirium and caution is advised; it is helpful to avoid long acting ones and those with active metabolites.

Serotonergic drugs tend to reduce certain kinds of aggressive behaviours so propranolol and pindolol can be helpful (they are 5-HT1A antagonists). SSRIs may also be used but may occasionally induce slight aggravatation of extra-pyramidal side effects and some of them cause interaction problems (see notes re CYP450).

Because of interactions and special pharmacological factors in the elderly this is a challenging area.

Easily precipitated delirium indicates prodromal dementia.

Also major surgery precipitates cognitive decline. A huge study of 1218 patients aged 60+ yrs were tested before and 1 week and 3 months after 'major' (non-cardiac) surgery. Postoperative cognitive dysfunction was present in 25.8% of patients 1 week after surgery and in 10% 3 months after surgery (compared with 3% of controls, p=0.0001). Age, duration of anaesthesia, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction. Only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. These findings have implications for clinical practice and the information given to patients before surgery.