Causes and treatment of reversible dementia

1. REVERSIBLE
DEMENTIA
By Ahmed Abdul Ghani

2. What is
Dementia?
According to the
Diagnostic and
Statistical Manual (DSM-
5) by American
Psychiatric association
2013, dementia is a
clinical syndrome
characterized by the
following

3. 1. Acquired loss of higher mental
functions affecting 2 or more of:
a) Short and /or long term memory
b) Language functions
c) Frontal executive functions

4. 2. Causing significant social or
occupational impairment
3. Being chronic and stable which
differentiate it from delirium

5. Epidemiology
Dementia is common among aging population, with
an estimated prevalence 6% above the age of 65
years and it increases to 20% above the age of 85
years

6. Dementia is usually irreversible.

7. REVERSIBLE DEMENTIA

8. ■ Reversible dementias are conditions that are
associated with cognitive or behavioral symptoms
that can be resolved once the primary etiology has
been treated.
■ The prevalence of the potentially reversible
disorders has been reported 18% under the age of
65 years but only 5% in those above 65 years.
■ However, there is some confusion over the term
‘reversible’ dementia as many causes of dementia
‘especially endocrine’ overlap with delirium.

9. ENDOCRINAL
CAUSES

10. THYROID
DISORDERS

11. Thyroid
disorders
Many patients with thyroid
disorders may present with
initial neurological
manifestations

12. The link between thyroid hormones
with mood and cognition:
■ Chopra IJ, and his colleagues reported in their study
that one third of patients with depression admitted to
psychiatry unit are found to have suppressed TSH
levels, moreover, the nocturnal surge of TSH is
frequently absent in depressed patients resulting in
reduction of thyroid hormone secretion (central
hypothyroidism).
Chopra IJ, Solomon DH, Huang TS. Serum thyrotropin in hospitalized psychiatric patients: evidence for hyperthyrotropinemia as measured by an
ultrasensitive thyrotropin assay. Metabolism 1990;39(5):538–43.
Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain mol cell neurosci. 2005;29(3):414-426
Hennessey JV, Jackson IM. The interface between thyroid hormones and psychiatry. Endocrinologist 1996;6:214–23.

14. ■ Thyroid hormones found to have important role in
hippocampal neurogenesis, myelination,
synaptogensis and gliogensis.
■ The reason for blunted TSH is still a subject of much
debate, however, glucocorticoids, known to inhibit
HPA axis are elevated in depression and could be
responsible.
Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain mol cell neurosci. 2005;29(3):414-426
Hennessey JV, Jackson IM. The interface between thyroid hormones and psychiatry. Endocrinologist 1996;6:214–23.

15. Hypothyroidism: overt and subclinical
■ 1% - 4% of patients with affective disorders are
hypothyroid and up to 40% have subclinical
hypothyroidism.
■ Treatment with levothyroxine improve
neuropsychiatric symptoms, although the pattern of
response in inconsistent and unpredictable.
Davis JD, Tremont G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol 2007;32(1):49–65.
Resta F, Triggiani V, Barile G, Benigno M, Suppressa P, Giagulli VA, et al. Subclinical hypothyroidism and cognitive dysfunction in the elderly. Endocr
Metab Immune Disord Drug Targets 2012;12:260-7.

17. ■ It was found that 30% - 40% of patients with
depression who do not respond to antidepressants
monotherapy, adjuvant therapy with levothyroxine
have been said to be logical when depression fails
to resolve after 6 weeks of adequate
antidepressant medication.
Hennessey JV, Jackson IM. The interface between thyroid hormones and psy- chiatry. Endocrinologist 1996;6:214–23

19. Thyrotoxicosis: overt and subclinical
■ Patients with thyrotoxicosis present with wide array of
neuropsychiatric manifestations, however, in elderly
population the presentation may include lethargy and
depression (apathetic thyrotoxicosis).
■ The neuropsychiatric manifestations associated with
hyperthyroidism do not always resolve after treatment
and restoration of euthyroid state.
Trzepacz PT, McCue M, Klein I, et al. A psychiatric and neuropsychological study of patients with untreated Graves’ disease. Gen Hosp Psychiatry 1988;
10(1):49–55.

20. Primary
hypoparathyroidism
Such patients usually
present with manifestations
related to hypocalcemia
(seizure, tetany, paresthesia
and muscle cramps),
however, atypical
presentation rarely
described including
neuropsychiatric
manifestations.

21. PUBLISHED CASES OF HYPOPARATHYROIDISM
AND NEUROPSYCHIATRIC MANIFESTATIONS

22. Hypercortisolism
Hypercortisolism and
chronic steroid
administration can cause
hippocampal atrophy.
Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV . Hypoglycemic episodes and risk of
dementia in older patients with type 2 diabetes mellitus. JAMA 2009;301:1565-72

23. ■ In 1932, Harvey Cushing highlighted the
neuropsychiatric disturbances in his original
description of a series of 12 Cushing syndrome
cases, he found emotional disturbances among
these patients.
■ The exact mechanism by which excess
glucocorticoids induce brain damage is not
known yet, however theories suggest that brain
damage may be related to decrease glucose
uptake by brain cells and suppression of
neurogenesis in the dentate gyrus.

24. ■ The most important neuropsychiatric
manifestations are major depression (up to 54% of
patients with Cushing syndrome), as well as
cognitive dysfunctions and anxiety.
■ Memory impairment has been reported in 83% of
patients with Cushing syndrome consisting in
difficulty in processing new information and
forgetfulness of information such as appointments,
names of people and places
Sonino, N., and Fava, G. A. (2001). Psychiatric disorders associated with Cush- ing’s syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs 15, 361–373.
doi: 10.2165/00023210-200115050-00003

25. ■ To date, the issue of whether remission of Cushing
syndrome may completely revert psychiatric and
neurocognitive dysfunction is controversial.
Hirsch, D., Orr, G., Kantarovich, V., Hermesh, H., Stern, E., and Blum, I. (2000) Cushing’s syndrome presenting as a schizophrenia-like psychotic
state. Isr. J. Psychiatry Relat. Sci. 37, 46–50

26. Drugs
Many medications can induce cognitive and memory disfunction

27. Steroids
■ Patients treated with steroids for prolonged
duration may develop impaired cognitive functions
that occur without psychosis.
■ This condition is rapidly reversible following steroids
tapering.

28. Anti-psychotic medications
■ Medications with anti-cholinergic properties as anti-
depressants and anti-psychotics can cause
cognitive and memory dysfunction
■ Benzodiazepines once considered safe
medications, however, a recent research found that
84% of patients attending psychiatric clinics are
chronic benzodiazepines users (more than 6
months).Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA
Intern Med 2015;175:401-7.
Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer’s disease: Case-control study. BMJ
2014;349:g5205.

29. NUTRITIONAL
CAUSES

30. Thiamine (B1) deficiency
■ Vitamin B1 enables the body to utilize
carbohydrates as a source of energy, thus it is
essential for glucose metabolism in nervous
system, skeletal and cardiac muscle.
■ Thiamine deficiency can result in Wernicke’s
encephalopathy in chronic alcoholics, characterized
by a triad of ophthalmoplegia, ataxia and
confusion.
■ Untreated Wernicke’s encephalopathy may
progress to Korsakoff syndrome characterized by
cognitive and memory dysfunction.Asada T, Takaya S, Takayama Y, Yamauchi H, Hashikawa K, Fukuyama H. Reversible alcohol-related dementia: A five-year follow-up study using FDG-PET
and neuropsychological tests. Intern Med 2010;49:283-7.

31. Cobalamin (B12) deficiency
■ Vitamin B12 is involved in the metabolism of every
cell of the human body, a cofactor in DNA synthesis,
and in both fatty acid and amino acid metabolism.
■ Deficiency results in a plethora of neuropsychiatric
symptoms, ataxia, paresthesia and muscle
weakness.
Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 1991;70:229-45

32. Iron deficiency
■ Recently, iron deficiency has been implicated in
cognitive dysfunction in elderly which is
independent of anemia.
■ Iron deficiency can promote reduction in systemic
and possibly central nervous system concentration
of growth factors and alter the expression and
function of insulin-growth-factor I & II.
Estrada JA, Contreras I, Pliego-Rivero FB, Otero GA. Molecular mechanisms of cognitive impairment in iron deficiency: Alterations in brain-derived neurotrophic factor and
insulin-like growth factor expression and function in the central nervous system. Nutr Neurosci 2014;17:193-206.

33. Vitamin D and Dementia
■ In 2015 a study published in JAMA Neurology
involved 382 participants with mean age of 75.5
years, found that vitamin D insufficiency may be
associated with significantly faster decline in both
episodic memory and executive function
performance, that may correspond to elevated risk
for incident Alzheimer’s disease
JAMA Neurol. 2015;72(11):1295-1303

34. CNS
INFECTIONS
Many CNS infections known
to cause reversible
cognitive impairment

35. Chronic bacterial meningitis
■ Patients with suppressed immunity are at
increased risk of developing chronic meningitis
manifested with confusion, cognitive dysfunction,
hearing loss as well as symptoms similar to acute
meningitis (headache, fever, and neck stiffness)

36. Neurosyphilis
■ Neurologic involvement can occur
decades after T. pallidum infection
■ Clinical manifestations can include;
cranial neuropathies (sensory),
dementia, personality change,
pupillary changes, tabes dorsalis
Mehrabian S, Raycheva M, Traykova M, Stankova T, Penev L, Grigorova O, et al. Neurosyphilis with dementia
and bilateral hippocampal atrophy on brain magnetic resonance imaging. BMC Neurol 2012;12:96.

37. HIV infection
■ HIV associated neurocognitive disorder
(HAND) encompass a range of
progressively more severe patterns of
neurological involvement ranging from
asymptomatic neurocognitive impairment
(ANI) to minor neurocognitive disorder
(MND) to more severe HIV-associated
dementia (HAD) (also known as AIDS
dementia complex or HIV encephalopathy)
Kolson DL, González-Scarano F. HIV and HIV dementia. J Clin Invest 2000;106:11-3.

38. Neurocysticercosis
(NCC)■ NCC is a result of accidental ingestion of
eggs of Taenia solium (pork tapeworm)
■ In developing countries, it is the most
common parasitic disease of the nervous
system and is the main cause of acquired
epilepsy and neurospychiartic dysfunction.
Ramirez-Bermudez J, Higuera J, Sosa AL, Lopez-Meza E, Lopez-Gomez M, Corona T. Is dementia reversible in
patients with neurocysticercosis? J Neurol Neurosurg Psychiatry 2005;76:1164-6.

39. NORMAL
PRESSURE
HYDROCEPHALUS
(NPH)

40. ■ NPH is an idiopathic condition characterized by
progressive ventricular dilatation
■ Triad of ataxia, urine incontinence and potentially
reversible dementia
■ Dramatic improvement of symptoms is noted
following a trial of CSF removal
■ Surgical CSF shunting remains the main treatment
modality
Panagiotopoulos V, Konstantinou D, Kalogeropoulos A, Maraziotis T. The predictive value of external continuous lumbar drainage, with cerebrospinal fluid
outflow controlled by medium pressure valve, in normal pressure hydrocephalus. Acta Neurochir (Wien) 2005;147:953-8.

41. Thank you