A 78 year old lady presented with fatigue, anxiety and depression. She had angular cheilosis but was not anaemic (Hb 11.9, MCV 90), despite a profound vitamin B₁₂ deficiency (11 ng/l) with normal serum and red cell folate (12 μg/l and 299 μg/L). She had parietal cell antibodies but a normal Schilling test. She '...felt better' after monthly injections of hydroxo-B₁₂ (1,000 μg) were commenced, but nevertheless remained anxious.

A year later she developed memory impairment, with difficulty remembering names. She scored 21/30 on Mini-mental state examination (MMSE) 25. It was felt that she had a dementia, perhaps with associated depression, and she was commenced on an antidepressant (a selective serotonin reuptake inhibitor). Her depression slowly resolved but her cognitive decline continued.

A year later she scored 18/30 on MMSE and 28/70 on the Alzheimer's disease assessment scale (ADAS-Cog) 26. In view of her persistent dementia despite regular hydroxo-B₁₂ injections, she was commenced on oral NAC (600 mg) daily (Zambon Italia – Vicenza). Two weeks later her husband reported a noticeable improvement in her memory. She now remembered names and faces she previously would have struggled to recall. Her MMSE improved to 21/30 and ADAS-Cog to 20/70. The areas of improvement were in scores of orientation, copying skills, word-recall, naming and commands.

An 84 year old lady presented with a three year history of short-term memory impairment and early Parkinsonism for which she took L-dopa. She was otherwise well. She scored 12/28 on the 6 Item Cognitive Impairment Test (6CIT) 27. Investigations revealed a total serum homocysteine (tHcy) of 20.1 μmol/L (normal range <13μmol/L), but normal serum vitamin B₁₂ (309 ng/L), folate (9.2 μg/L) and red cell folate (464 μg/L). She was not anaemic, but had borderline hypothyroidism (TSH 9.1 μmol/L).

In view of her elevated tHcy, and despite 'normal' serum B vitamin levels, she was commenced on daily oral cyano-B₁₂ (1000 μcg), folic acid (5 mg) and NAC (600 mg). Within one month her tHcy fell to 7.5 μmol/L. She was assessed by a Psychogeriatrician three months after her initial presentation. She now showed no significant cognitive deficits; she scored 28/30 on MMSE.

The psychogeriatrician was '...particularly impressed that she could provide the Christian names of all her five children and twelve grandchildren without any problems' and it was felt that she now had no obvious diagnosis of a dementing illness.

A 77 year old lady presented with a six month history of confusion and memory loss. An aunt had early-onset AD. On examination she was disorientated to time and had demonstrable memory impairment. She was vitamin B₁₂ deficient (172 ng/L) but with normal serum and red cell folate (10.1 μg/L and 321 μg/l, respectively).

She commenced monthly intramuscular hydroxo-B₁₂ injections (1,000 μg) but continued to deteriorate. She became fatigued and developed visual hallucinations and persecutory ideas. She had naming difficulties, her repetition was poor, and she had constructional dyspraxia. It was felt she had probable AD. She was admitted for care, scoring only 13/30 on MMSE. She was commenced on an acetylcholinesterase inhibitor with slight initial improvement (15/30). Nevertheless her condition continued to deteriorate. She developed dysphagia and weight loss due to a grade III oesophagitis.

Oral NAC (600 mg daily) was added to her treatment and her family and carers noticed a significant improvement. She became more alert and recognised her close family; a formal cognitive assessment was not performed in view of the severity of her dementia and associated physical condition. Sadly she died from a bronchopneumonia several weeks later.

An 87 year old retired school headmistress presented with a three year history of gradually deteriorating short-term memory and general 'confusion'; she frequently mislaid things and often wandered, forgetting her way home. She had a past medical history of diverticular disease and an osteoarthritic hip, but was otherwise well.

On examination it was felt she was suffering from a senile dementia of moderate severity although no formal cognitive scores were recorded. Routine investigations were normal other than a highly elevated tHcy of 27.5 μmol/L.

She was commenced on folic acid 5 mg daily and oral hydroxo-B₁₂ 1,000 mcg daily, together with NAC 600 mg daily. Her tHcy fell to 6.6 μmol/L six-months later, at which time she felt generally well although she remained mildly confused. Her daughter commented on a marked improvement in her general behaviour, although she remained forgetful at times. Three years later she remains very well and continues to be cared for at home with no major difficulties.

An 84 year old lady presented with a two year history of increasing forgetfulness and confusion and no significant previous illnesses. She was cared for at home by her daughter. On formal examination she was disorientated in time and place with demonstrable short-term memory impairment.

It was felt she had a moderate dementia; she scored 55 out of 70 on an ADAS-Cog assessment. Blood investigations were normal other than an elevated tHcy of 16.4 μmol/L and low red cell folate (157μg/l) (serum vitamin B₁₂ and folate were 281 ng/L and 4.4 μg/l respectively.) She was not anaemic (Hb 12.7).

She was commenced on daily oral cyano-B₁₂ (150 μg daily) folic acid (5 mg) and NAC (600 mg) daily. One month later she had gained ten points on ADAS-Cog score. Her daughter also reported that she was '...generally more settled and content, and less likely to wander.'

A 71 year old retired engineer presented with a ten year history of gradually progressive short-term memory impairment. His wife had become concerned because he had recently lost his way driving to a regular address. He complained of losing objects and forgetting people's names.

His father had died of senile dementia aged 74, with symptoms developing at aged 60 years. The patient himself had a past medical history of hypertension controlled by beta-blocker. On cognitive examination he scored poorly on 6CIT (12/28). Routine blood investigations revealed elevated tHcy (15.6 μmol/L) with normal serum vitamin B₁₂ (368 ng/L), folate (9.3μg/L) and red cell folate (492 μg/L).

He was commenced on daily oral cyano-B₁₂ (1,000 μg) folate (5 mg) and NAC (600 mg). His wife reported a "...definite and immediate improvement" within two weeks of commencing treatment. His tHcy fell to 9.6 μmol/L. He was seen by a Psychogeriatrician one month later. He now scored 28/30 on MMSE with a CAMCOG of 115/125, indicating only a mild cognitive deficit 28. A diagnosis of "age-related cognitive impairment" was made. He has continued on this treatment for the last two years and continues to score well on cognitive assessments. He scored 27/30 on his most recent assessment and has now commenced an acetylcholinesterase inhibitor in addition to B vitamin and NAC supplementation.

A 75 year old retired College Lecturer presented with a four year history of increasing forgetfulness. In particular he frequently mislaid things, and had occasional difficulty remembering people's names. His wife had become concerned about his ability to drive. He had a past medical history of prostatic carcinoma treated with radiotherapy, anxiety/depression, and gastro-oesophageal reflux, but was generally well in himself.

On cognitive examination he was disorientated in time and had demonstrable short term memory impairment. He scored 8/28 on 6CIT and 16/39 on TICS-m 29. An MRI scan showed several foci consistent with small vessel disease (Figure 1). Blood investigations revealed raised tHcy of 14.6 μmol/L, borderline low serum B₁₂ (191 ng/L), but normal folate (11.7 μg/L) and red cell folate (692 μg/L).

He was commenced on daily oral cyano-B₁₂ (1000 μg), folic acid (5 mg) and NAC (600 mg). After one month he had gained five points on TICS-m (21/39). His tHcy fell to 8.3 μmol/L. He was personally delighted with the treatment. His wife commented that "...he was becoming very forgetful, quite retiring, quiet, sleepy all the time, not interested in his food or in life. Now, there's a marked improvement. We can discuss the news without any problem. He's reading again. He's interested in life once more."

One year later, he remains well and has successfully regained his driving license following a formal assessment. A repeat MRI scan showed no significant progression in the extent or size of the focal areas of abnormality in the deep white matter, and no change in ventricular configuration (Figure 2).