Differential diagnosis between Alzheimer's disease and hypothyroidism in adults with Down syndrome

The differential diagnosis between Alzheimer's disease and hypothyroidism in adults with Down syndrome who begin to show clinical deterioration needs to be emphasised. This study investigated clinical features which could be used to differentiate between the two conditions. Memory loss, mood and personality change, speech and gait deterioration, and slowing down were significantly associated with dementia but not with hypothyroidism. It is recommended that specific questions should be asked to elicit the presence of these features particularly in those individuals in whom assessment of biochemical thyroid status is not possible.

Prasher, V. (1995) Differential diagnosis between Alzheimer's disease and hypothyroidism in adults with Down syndrome. Down Syndrome Research and Practice, 3(1), 15-18. doi:10.3104/reports.46


An association between Alzheimer's disease and Down syndrome (Oliver & Holland, 1986; Prasher & Krishnan, 1993) and between thyroid dysfunction and Down syndrome (Dinani & Carpenter, 1990; Prasher, 1994) have been well established. Both Alzheimer's disease and thyroid dysfunction occur more commonly in older individuals with Down syndrome and both disorders can present with decline in cognitive skills, physical deterioration and loss of adaptive skills. Differentiation between the two disorders can, therefore, be difficult.

Although assessment for biochemical thyroid status should be undertaken in all individuals who present with clinical deterioration, performing blood tests in people with Down syndrome, especially in older individuals, can at times be difficult (Prasher, 1994). It is, therefore, important to establish whether hypothyroidism can be differentiated from changes indicative of dementia on clinical grounds alone. Although studies have reported clinical changes of Alzheimer's disease in adults with Down syndrome (Oliver and Holland, 1986), and other studies have reported thyroid dysfunction changes in people with Down syndrome (Mani, 1988, Prasher, 1995), no study to date has investigated the clinical differentiation between Alzheimer's disease and hypothyroidism in people with Down syndrome. This study reports findings for 74 subjects.


As part of the West Midlands Ageing Study individuals with Down syndrome were being investigated for thyroid dysfunction and changes of Alzheimer's disease. This study had a large sample size, a wide age range (16-75 years) and institutionalised and community residents. The sample was relatively representative of adults with Down syndrome in the region. All individuals were, where possible, assessed cytogenetically to determine the presence of Down syndrome.

For the study reported here a number of individuals with biochemical hypothyroidism and mild or moderate Alzheimer's disease according to DCR-10 criteria (WHO,1993) were identified. To exclude effects of institutionalisation only community residents were investigated. Persons with no evidence of hypothyroidism, dementia or any other significant psychiatric disorder were used as controls.

Subjects in all three groups were assessed for a number of symptoms and signs used to diagnose clinical hypothyroidism (Mani, 1988) and symptoms and signs used to diagnose dementia (Evenhuis, 1990). Primary carers were interviewed and individuals examined to elicit presence of such symptoms and signs.

Biochemical hypothyroidism was diagnosed when free thyroxine values were below 12 pmol/l (normal range 12-26 pmol/l) and thyroid stimulating hormone levels were over 4.0 microIU/ml (normal range 0.3-4.0 microIU/ml). For the dementia group, only individuals with mild or moderate dementia according to ICD-10 criteria (WHO, 1992) were used as a comparative group. People with severe Alzheimer's disease were not assessed as differentiation of severe dementia from hypothyroidism should not be difficult.

Further to the checklist of symptoms, comparison of adaptive function was also undertaken. The Adaptive Behaviour Scale (ABS) (Nihira, 1974) was used. This is a widely used and well established instrument for assessment of adaptive function. Domain and total scores for Part I and Part II were used. Part I assessed independent functioning and Part II maladaptive behaviours. Domain 14 of Part I `use of medication' was excluded. Comparative analysis for the three groups was undertaken.


Seventy-three individuals were assessed. Demographic details are given in Table 1. The dementia group was found to be significantly older. The mean thyroxine level for the hypothyroid group was 8.58 (SD 2.74) with a mean thyroid stimulating hormone value of 28.58 (SD 33.67).

Table 1. Demographic details of hypothyroid, dementia and control groups.

Feature Dementia Group
Hypothyroid Group
Control Group
Age Mean (SD) 50.9 years (6.9) 42.9 years (13.2) 38.9 years (9.1) Dementia group sig older (ANOVA p<0.5)
Range 39-72 years 25-62 years 20-62 years
Sex Male 47% 42% 57% No sig difference at 5% level
Female 53% 58% 43%
Residence Family Home 47% 67% 52% No sig difference at 5% level
Community Home 53% 33% 48%
Severity of
Mild 18% 25% 23% No sig difference at 5% level
Moderate 76% 67% 73%
Severe 6% 8% 2%
Unknown 2%
History of Hypothyroidism 4 1 4
SD = standard deviation. sig = significant.

Findings for frequency of symptoms and signs are given in Table 2. Several features were found to occur in both dementia and hypothyroidism groups. However, memory loss, emotional change, slowing down, personality change, speech and gait deterioration were found to be statistically significantly associated with dementia but not with hypothyroidism. Increased dry skin and weight change were more frequent in the hypothyroid group but not at the 5% significant level.

Table 2. Clinical findings for hypothyroid, dementia and control groups.

Feature Dementia
group %
group %
group %
Findings for
and dementia
Memory loss 100 17 2 Z= 4.6 P<0.01
Personality change 53 17 2 Z=2.0 P<0.5
Mood change 76 25 2 Z= 2.7 P<0.01
Behavioural deterioration 29 8 4 Z= 1.4 NS
Slowing down 88 33 11 Z= 3.0 P<0.01
Speech deterioration 71 17 2 Z= 2.8 P<0.01
Gait deterioration 76 25 0 Z= 2.7 P<0.01
Onset urinary incontinence 35 17 0 Z= 1.1 NS
Onset seizures 30 17 0 Z= 0.1 NS
Increased muscle tone 24 17 0 Z= 0.4 NS
Hair loss 24 17 18 Z= 0.4 NS
Dry skin 47 58 34 Z= 0.7 NS
Reduced appetite 24 0 0 Z= 1.7 NS
Disturbed sleep pattern 30 8 2 Z= 1.4 NS
Weight change 2 8 2 Z= 0.3 NS
* = Non-parametric analysis. Mann-Whitney test. NS = Not significant.

Both the dementia and hypothyroid groups scored significantly lower on Part I of the ABS than the control group (Table 3). The dementia group scored lower than the hypothyroid group for virtually all domains and total Part I scores but this was not statistically significant at the 5% level. Both groups scored higher on the Part II (maladaptive behaviours) than the control group, with the dementia group scoring the highest. No particular ABS domain could be used to differentiate dementia from hypothyroidism.

Table 3. Adaptive behaviour scale scores for hypothyroidism, dementia and control groups.

Domain Dementia Group
Mean (SD)
Group Mean (SD)
Control Group
Mean (SD)
Part I Independent functioning 53.24 (19.53) 54.25 (21.61) 74.77 (12.48)
Physical development 16.24 (5.04) 15.92 (5.48) 20.25 (2.74)
Economic activity 1.35 (2.00) 1.83 (2.41) 3.80 (3.17)
Language development 12.47 (5.81) 14.50 (8.17) 18.98 (6.81)
Numbers and time 2.47 (2.60) 3.08 (3.82) 4.77 (3.24)
Domestic activity 4.24 (4.51) 5.00 (5.34) 9.18 (4.18)
Vocational activity 1.29 (2.89) 1.50 (3.53) 4.27 (4.76)
Self-direction 8.53 (3.73) 9.08 (3.99) 13.50 (4.31)
Responsibility 1.53 (1.55) 2.17 (1.85) 3.34 (1.83)
Socialization 11.82 (4.81) 14.67 (6.85) 17.70 (4.22)
Part I overall score 113.18 (41.42) 122.00 (52.41) 170.37 (37.93)
Part II Violent and destructive behaviour 5.53 (4.12) 2.17 (2.48) 0.61 (1.30)
Antisocial behaviour 3.71 (9.90) 2.42 (2.71) 0.82 (1.45)
Rebellious behaviour 5.35 (8.94) 0.67 (1.23) 0.57 (1.15)
Untrustworthy behaviour 1.35 (3.84) 1.75 (2.83) 0.50 (1.28)
Withdrawal 5.65 (6.17) 2.58 (4.21) 1.64 (3.21)
Stereotyped behaviour 0.82 (1.42) 0.58 (1.16) 0.30 (0.76)
Inappropriate interpersonal manners 0.82 (2.43) 0.42 (0.79) 0.27 (0.66)
Unacceptable vocal habits 1.35 (2.37) 0.67 (1.61) 0.27 (0.62)
Unacceptable or eccentric habits 2.47 (4.11) 0.83 (1.85) 1.23 (2.33)
Self-abusive behaviour 0.35 (0.70) 0.25 (0.62) 0.23 (0.64)
Hyperactive tendencies 0.29 (0.85) 0.00 (0.00) 0.00 (0.00)
Sexually aberrant behaviour 1.00 (2.67) 0.25 (0.62) 0.27 (0.90)
Psychological disturbances 4.29 (9.27) 1.92 (0.62) 1.30 (2.36)
Part II overall score 30.00 (44.90) 14.50 (10.77) 8.00 (9.86)
No statistically significant difference for domain and total scores between hypothyroid and dementia groups.


This study demonstrates that there are clinical differences in the presentation of mild/moderate Alzheimer's disease and hypothyroidism in adults with Down syndrome. Deterioration in memory, changes in mood and personality, deterioration in speech and gait and bradykinesia are strong indicators of Alzheimer's disease rather than hypothyroidism. Ultimately, biochemical analysis for thyroid status would clarify the position, although such tests would be better supported and be more cost effective if there was greater suspicion on clinical grounds.


  1. Bradykinesia: Difficulty in initiating and executing movements.
  2. Cytogenerically: Related to genetic structure of the cell.
  3. Hypothyroidism: Subnormal activity of the thyroid gland.
  4. Thyroxine: Thyroid hormone.


Picture of a child with Down syndrome learning to read

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